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Institute of Public Health of Serbia ”Dr Milan Jovanovic Batut”
Attributable Causes of Cancer
in Serbia in the Year 2005
Belgrade, 2008
2
Director of Institute of Public Health of Serbia ”Dr Milan Jovanovic Batut”
Tanja Knezevic, MD, PhD
Department for Prevention and Control of Noncommunicable Diseases
Dragan Miljus, MD, M. Sc., epidemiologist
Snezana Zivkovic, MD, epidemiologist
Snezana Plavsic, MD, epidemiologist
Jelena Jankovic, MD,
Sanja Savkovic, statistics engineer
Consultants
Prof. dr Hristina Vlajinac, MD, PhD, Academy of medical sciences Srpskog lekarskog društva
Prof. Sandra Sipetic Grujicic, MD, PhD, Institute of epidemiology, Faculty of medecine, Belgrade
Prof. Jelena Marinković, MD, PhD, Institute of medical statistics and informatics, Faculty of
medecine, Belgrade
Prof. Marica Miladinov Mikov, MD, PhD, Oncology Institute of Vojvodina, Sremska Kamenica,
Faculty of medecine, Novi Sad
Lidija Stankovic, dipl. engineer of information systems
Neda Stojanovic, dipl. mathematics
Sonja Mitov Scekic, dipl. mathematics
Reviewers
Prof. dr Hristina Vlajinac, MD, PhD
Prof. Sandra Sipetic Grujicic, MD, PhD
Translator
Vesna Kostic
3
Table of contents
1. Background .................................................................................................................................... 4
2. Objectives ....................................................................................................................................... 5
3. Methodology .................................................................................................................................. 5
3.1 Incidence data ................................................................................................................... 5
3.2 Mortality data ................................................................................................................... 6
3.3 Population data ................................................................................................................. 6
3.4 Classifications of diseases, causes of diseases and death ................................................. 6
3.5 Cancer risk factors in Serbia ............................................................................................. 7
3.6 Prevalence and exposure in Serbia ................................................................................... 7
3.7 Calculation of the attributable fraction ............................................................................. 8
3.8 Sensitivity analysis ........................................................................................................... 8
4. Cancer incidence and mortality in Serbia ....................................................................................... 9
4.1 Discussion ....................................................................................................................... 14
4.2 Cancer incidence and mortality rates in Serbia, 2005 ................................................... 15
5. Burden of leading risk factors in Serbia ........................................................................................18
6. Selected cancer risk factors in Serbia ........................................................................................... 20
6.1 Tobacco smoking ............................................................................................................ 21
6.2 Alcohol drinking ............................................................................................................. 30
6.3 Overweight and obesity .................................................................................................. 34
6.4 Physical inactivity ........................................................................................................... 38
6.5 Chronic infections ........................................................................................................... 41
6.6 Use of oral contraceptives .............................................................................................. 45
6.7 UV radiation ................................................................................................................... 48
7. Results .......................................................................................................................................... 51
8. Discussion .................................................................................................................................... 55
4
Background
Malignant tumors are a group composed of numerous diseases of various localizations,
morphology, clinical presentations and prognosis. Nowadays, these diseases are among the leading
causes of morbidity, absenteeism and disability as well as early death worldwide.
Malignant tumors have multifactorial etiology and result from complex interaction between
individuals and environment they live in. Many risk factors associated with the occurrence of
cancer may be linked to the lifestyle, environmental conditions or inheritance. Individual, socio-
economic and environmental features define the differences in exposure and susceptibility of
individual for the occurrence of cancer.
The lifestyle and environmental conditions that may lead to the occurrence of cancer are
frequently subject to debate, particularly those relating to “environmental factors” are frequently
differently interpreted. The number of risk factors linked with cancer increases over time, and it is
believed that quite a number of them are yet to be discovered.
Leading risk factors for the occurrence of cancer include smoking, obesity (irregular diet and
physical inactivity), infections, reproductive and sexual behavior, occupation, alcohol drinking and
environmental factors (ionizing and non-ionizing radiation, air pollution). It is estimated that only 2
to 4% of all cancer localizations may be associated with genetic defects. The role of numerous risk
factors in carcinogenesis is only inferred, but not yet evidenced.
Most of the aforementioned risk factors can frequently be associated with at least two
locations of malignancies, and not rarely with more other chronic diseased. In many individuals,
these risk factors are clustered, and their interaction frequently results in multiplication effect.
The current level of knowledge makes it possible to prevent the occurrence of many
malignant tumors. When resources and support are available, at least one third of malignant tumors
could be diagnosed early and treated successfully.
The report provides an evaluation of newly diagnosed cancer cases and cancer deaths that
could be attributed to non-genetic risk factors.
In 2005 cardiovascular diseases and malignant tumors accounted for over three quarters of all
causes of death in Serbia. Over a half of fatal outcomes in Serbia (56.8%) resulted from diseases of
the heart and blood vessels, and almost one in five deaths (18.5%) resulted from a malignant
tumor; 3.6% , 2.7%, and 2.4% of the Serbian population died of injuries & poisoning, chronic
respiratory diseases, and complications of diabetes, respectively.
In comparison with 1985, the greatest rise in this mortality structure in 2005 was noted for
malignant tumors (3.8%).
5
2. Objectives
The purpose of the report is to assess the number of cancer cases and cancer deaths in Serbia
that may be attributable to factors of demonstrated carcinogenicity.
3. Methodology
Assessments of attributable risk factors are presented as proportions of specific cancer
localizations in Serbia (2005) that could be attributed to selected, specific risk factors. The
proportion of cancer in the population of Serbia that could be attributed to a risk factor is called the
attributable fraction and is expressed as a percentage.
The most straightforward method of attributable fraction (AF) assessment for the risk factors
that could, at least theoretically, be avoided or completely eliminated, is to calculate the fraction of
all cancer cases (exposed and unexposed to a certain factor) that would have not occurred if
exposure had not occurred. In AF assessment for this report, it is assumed that unexposure does not
imply total absence, but the presence of minimum levels of exposure to carcinogens instead.
3.1 Incidence data
Although the national population cancer register in Serbia was established as early as 1970,
the incidence data on malignant tumors in our country have been provided only recently. There are
two population cancer registers in Serbia: one for central Serbia and the other for Vojvodina.
In 2005 there was no central nationwide cancer register. The data on new cancer cases for
the year were provided from the published data of the Central Serbia Cancer Register and
unpublished (preliminary) data of the Vojvodina cancer register.
Based on the two population registers, this report presents the assessed number of new
cancer cases in Serbia in 2005. In addition to the total number of new cancer cases, we also
presented the most common malignancies in men and women and their crude incidence rates. The
report also presents not only the nonstandardized, but also standardized incidence rates. The stated
rates were standardized using the direct standardization methods, and the population of Europe was
used as the standard.
6
3.2 Mortality data
We used the unpublished data of the on cancer mortality in Serbia for the period 1985-2005.
The specified data were analyzed at the Institute of Public Health by the standard five-year age
intervals, sex and cancer localizations.
In addition to non-standardized ones, mortality rates standardized for the population of
Europe are also presented.
3.3 Population data
Population estimates for the period 1985-2005 were used as sources of population data by
the five-year age intervals and sex in Serbia, except for 1991 and 2002 when the data were obtained
from the respective censuses. The data were taken over from the National Statistics Bureau.
The Republic of Serbia is composed of three administrative units: Central Serbia and two
autonomous provinces (Vojvodina and Kosovo). Since the data for Kosovo have not been available
ever since 1997, the presented data in this study relate to the territory of Serbia without Kosovo.
3.4 Classifications of diseases, causes of diseases and death
Malignant tumors were coded pursuant to 10th Revision of International Classification of
Diseases (ICD-10), volume 1- (codes C00-C96) and International Classification of Diseases for
Oncology - Third Edition (ICDO-3) (codes 8000/3-9941/3) -. World Health Organization. 2000.
Geneva. “In situ” tumors are not covered by this report (codes D00-D09).
In the period 1985 to 1996 in Serbia malignant tumors were coded pursuant to 9th Revision
of International Classification of Diseases (ICD-9), volume 1- (codes. 140-208). In the stated
period, colorectal cancer (ICD-9: codes 153-154), included the codes of anal cancer (ICD-9: codes
154.2-154.8). Since cancer codes could not be analyzed by the four-digit code, the anus code was
added to the colorectal cancer code.
Lung cancer (ICD-9: code 162) included tracheal cancer (ICD-9: code 162.0). Due to the
reason stated above, the code of the tracheal cancer was added to the lung cancer code.
Presentation of data on colorectal cancer and lung cancer coded by ICD-10 uses the same
principle. Colorectal cancer (ICD-10: codes C18-C21), in addition to colon cancer and rectum
cancer (ICD-10: codes C18-20), included anus cancer (ICD-10: code C21), as well; similarly, lung
cancer (ICD-10: code C34) included tracheal cancer (ICD-10: code C33).
7
Malignant localizations of new cases of colorectal cancer and lung cancer were presented
using the same principle.
3.5 Cancer risk factors in Serbia
From the pool of risk factors, this report focused primarily tobacco, alcohol, oral
contraceptives, chronic infections and UV radiation that are classified as group 1 of agents
causatively associated with cancer, pursuant to IARC (http://monographs.iarc.fr). These factors
were compounded by overweight and obesity as well as physical inactivity since there is a sufficient
body of evidence to show that maintenance of normal body weight (avoidance of overweight and
obesity) and physical activity have preventive effect on some malignant tumors.
3.6 Prevalence and exposure in Serbia
In 2005 in Serbia cancer morbidity and mortality resulted from past exposure of the
population to risk factors. For most of malignant tumors, the latency between initial exposure and
occurrence of cancer is 15 years, meaning that exposure to risk factors in 1990 should be
considered.
Unfortunately, there are no available data on the prevalence of the selected risk factors in
1990. In early nineties and in the course of the decade Serbia experienced a turbulent period of
country disintegration, war and migrations.
So far, two (in 2000 and 2006) representative estimates of risk factor prevalence were made,
based on standard methodology employed by the World Health organization (WHO).
For evaluation of prevalence of exposure to risk factors in 1990 we used the model of linear
interpolation and available data of exposure to risk factors from 2000 and 2006 health surveys.
8
3.7 Calculation of the attributable fraction
Attributive fraction (AF) was calculated pursuant to Levin’s method:
AF= P(RR-1)/ [P(RR-1)] +1,
where RR is the elative risk for the occurrence of cancer resulting from exposure to a risk factor,
and P is the prevalence of the given factor in the population.
The relative risk for certain malignant tumors associated with exposure to tobacco, oral
contraceptives, chronic infections, UV radiation, overweight and obesity and physical inactivity
have been taken over from the already cited IARC where the RR estimate was based on the data
provided by meta-analysis comprising most representative studies. For continuous variables, such
as alcohol drinking, the relative risk was calculated pursuant to the following formula:
RR = Exp [(Ln (risk per unit)*average level of exposure)].
The cancer risk per unit of exposure represents the increase of cancer risk per unit of
increased exposure and has been taken over from the already cited IARC. The average level of
exposure in grams of alcohol per day was estimated for the population of Serbia on the basis of data
obtained from the National Statistics Bureau on consumption of food and beverages.
Since it is assumed that each individual experiences similar average exposure, we used a
simplified Levi’s formula for direct AF calculation:
AF = Risk - 1 / Risk
3.8 Sensitivity analysis
Different duration of the latent period between the first exposure and diagnosis of cancer, as
well as years for which the data on the risk factor prevalence were available greatly determine the
AF sensitivity analysis.
When total absence of exposure was not present for a risk factor, sensitivity analysis was
conducted by alternative approaches to exposure.
9
References E. Giovannucci. G. A. Colditz. S. Hankinson aCancer Causes & Control. An International
Journal of Studies of Cancer in Human Populations. Harvard University. Boston. MA. USA. 2006
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Overall
Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42. Supplement
7. Lyon. 1987.
Armitage P. Berry G. Statist cal Methods in Medical Research. second ed.. London.
Blackwell Scientific Publications. 1987
http://www.cdc.gov/cancer/cancerburden/
http://monographs.iarc.fr/
Attributable Causes of Cancer in France in the Year 2000. WHO. IARC. 2007
Ken-ichi Kamo, Satoshi Kaneko, Kenichi Satoh, Hirokazu Yanagihara, Shoichi Mizuno,
and Tomotaka Sobue. A Mathematical Estimation of True Cancer Incidence Using Data from
Population-based Cancer Registries. Jpn J Clin Oncol 2007;37(2)150–155.
10
4. Cancer incidence and mortality in Serbia
Data on the cancer incidence have been taken from the Central Serbia Cancer Registry,
which is available for 1999-2005 only. The cancer mortality data is taken from the National
Statistics Office, relating to 1985-2005. The incidence and mortality rates are calculated per
100,000 population and age-standardized to the population of Europe.
Figures 1-3 present the standard incidence rates for all malignant tumor and most common
malignant tumors in men and women in Central Serbia.
In comparison with 1999 the incidence of all cancer localizations in Central Serbia (Figure
1) rose by 21.8% (from 321.3/100,000 to 391.5/100,000) in men and by 16.8% (from 276.3/100,000
to 322.7/100,000) in women.
Figure 1. Cancer incidence rates by sex. Central Serbia. 1999-2005
250
300
350
400
450
1999 2000 2001 2002 2003 2004 2005
Years
Sta
nd
ard
ize
d r
ate
s p
er
10
0 0
00
Standardized rates per 100,000 (European standard population) Source: published data from Cancer Registry of Central Serbia. Institute of Public Health of Serbia
In the studied period, men most often contracted cancer of the lungs, colon and rectum,
prostate, urinary bladder, stomach and pancreas (Figure 2). From 1999 to 2005 a rising trend was
noted for all leading tumor sites except for the gastric cancer in men. In comparison with 1999, in
2005 the standardized incidence rate was increased by 60.3% in prostate malignancies, by 36.6%
for urinary bladder cancer, by 28.6% for colon and rectum cancer, and by 15.5% for lung cancer.
Males
Females
11
Figure 2. Most frequent cancers in males - incidence by sites, Central Serbia, 1999-2005
0,0
20,0
40,0
60,0
80,0
100,0
1999 2000 2001 2002 2003 2004 2005
Years
Sta
nd
ard
ize
d ra
tes
pe
r 1
00
00
0
Standardized rates per 100,000 (European standard population) Source: published data from Cancer Registry of Central Serbia. Institute of Public Health of Serbia
In women, the malignant process was most commonly localized on the breast,
colon&rectum, uterine cervix, lungs, uterus and stomach (Figure 3). With some variations in the
incidence values, in 1999-2005 a rise was noted in incidence rates for all leading sites of
malignancy, except for cervical cancer (Figure 3) where an incidence fall of 3.5% (from
31.3/100,000 to 30.2/100,000) was recorded. The incidence rates are increased by 24.6% for
colon&rectum malignancies, by 23.7% for lung cancer, by 17.1% for uterus and by 6.8% for
breasts.
Figures 4-5 illustrate standardized mortality rates for all malignancies and most common
malignancies in male and female population of Serbia.
In 1985 to 2005 rise of pooled mortality of all malignant tumors (Figure 4) by 34.5%
(188.5/100,000 to 253.6/100,000) was recorded in males, and by 28.0% (124.3/100,000 to
159.1/100,000) in females.
Most common causes of death in both males and females were the same malignancies that
were the most common causes of morbidity.
Lung (C33-34)
Colon-rectum (C18-21)
Prostate (C61) Urinary bladder (C67)
Stomach (C16)
12
Figure 3. Most frequent cancers in females - incidence by sites, Central Serbia, 1999-2005
0
25
50
75
100
1999 2000 2001 2002 2003 2004 2005
Years
Sta
nd
ard
ize
d r
ate
s p
er
10
0 0
00
Standardized rates per 100,000 (European standard population) Source: published data from Cancer Registry of Central Serbia. Institute of Public Health of Serbia
Figure 4. Cancer mortality rates by sex, Republic of Serbia. 1985-2005
100
200
300
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Years
Sta
nda
rdiz
ed r
ate
per
100
00
0
Standardized rates per 100,000 (European standard population) Source: unpublished data from Serbian National Statistics Office
Breast (C50)
Cervix (C50) Colon-rectum (C18-21)
Lung (C33-34) Corpus uteri (C54)
Males
Females
13
In the twenty-year period (1985-2005) increased mortality of all leading malignancies in
males (Figure 5) except for the stomach cancer was recorded. Standardized stomach cancer
mortality rates fell by 5.0% (from 19.2/100,000 to 16.7/100,000). In the same period, however, the
mortality rates related to colon&rectum malignancies rose by 69.4%, prostate by 52.6%, lung
cancer by 50.4%and pancreas by 35.2%.
Figure 5. Most frequent cancer mortality by sites, males, Republic of Serbia, 1999-2005
0
20
40
60
80
100
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Years
Sta
nd
ard
ize
d r
ate
s p
er
10
0 0
00
Standardized rates per 100,000 (European standard population) Source: unpublished data from Serbian National Statistics Office
In the same period, the rise of mortality rates of all leading cancer sites (Figure 6), except
for the stomach cancer that is associated with a fall of mortality rate by 22.9% (from 10.5/100,000
to 8.1/100,000). Over the studied period, the mortality rates associated with lung cancer rose by
77.8%, breast cancer by 52.3%, colon&rectum cancer by 46.8% and cervical cancer by 23.8%.
Lung (C33-34)
Colon-rectum (C18-21)
Prostate (C61)
Stomach (C16) Pancreas (C25)
14
Figure 6. Most frequent cancer mortality by sites, females, Republic of Serbia, 1999-2005
0
10
20
30
40
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Years
Sta
nd
ard
ize
d ra
tes
pe
r 1
00
00
0
Standardized rates per 100,000 (European standard population) Source: unpublished data from Serbian National Statistics Office
4.1 Discussion
Doll and Peto systematized the reasons that may lead the changes in cancer incidence and
mortality. They suggest changes in classifications of diseases (histological and other), completeness
of registration, population, diagnosis, early detection and screening, exposure to risk factors or
protective factors that may be related to the cancer incidence and effectiveness of treatment. .
The period for which we have the data on the incidence of malignancies in Central Serbia is
too short to provide grounds for any trend-wise conclusions. It is, nevertheless, a fact that the
incidence changes follow the mortality trend in the 20-year period. Rises of incidence of all
malignancies (pooled data) and all leading sites, except for the stomach cancer could, probably, be
attributed to better coverage and reporting of new cases of cancer. Since 2000, the reporting system
for malignant tumors included persons covered by military health insurance (Military Medical
Academy and military health centers) that significantly increased the registration coverage in
Serbia. Continuous education of medical staff at the National Cancer Registry in Serbia over the
same period has also contributed significantly to reporting of malignant tumors.
Lung (C33-34)
Colon-rectum (C18-21)
Breast (C50)
Cervix (C53)
Stomach (C16)
15
The rise of mortality may also be explained by improved diagnostics and reduced share of
symptoms and unspecified conditions as causes of death, particularly in the initial part of the
studied period, and also reduced success rate of treatment of malignancies during the economic
sanctions in Serbia in the last decade of the twentieth century.
However, lack of educational programs for primary and secondary preventions is the most
probable cause of the increased cancer- associated mortality and morbidity in Serbia.
In 1986 the EU members states launched a joint program entitled “Europe Against Cancer”
in order to reduce the cancer mortality in the region by 15% by 2000. Owing to campaigns
conducted in these countries, primarily anti-smoking ones, screening (cervix, breast and colon-
rectum) and activities on health promotion, the cancer mortality was reduced by 9% on the average
(10% and 8%, in men and women, respectively). In Serbia, most of these activities are not in place.
Serbia joined the anti-smoking campaign only recently, and the prevalence of smokers, particularly
among men, is among the highest in Europe. According to the data obtained from a population
health research conducted by the Public Health Institute in 2000, nutrition of the Serbian population
is rich in fat and sugar, with little fresh fruit and vegetables, with consequent high percentage of
obese and physically inactive people. Screening programs for cancer of the cervix, breast and colon
are only in the preparatory stage or just launched (for cervical cancer). Insufficient awareness of the
population on the importance of early treatment is another factor that contributes to poor prognosis
of these diseases
Fall of incidence and mortality associated with stomach cancer for both sexes in Serbia was
noted in most European countries, as well. The reasons for decreased incidence and mortality rates
associated with this cancer site are most probably linked with widespread use of antibiotics active
against Helicobacter pylori, and food preservation by freezing instead of the use of salt and smoke.
We have also investigated the possibility of the influence of population factors on the cancer
mortality in Serbia in the last two decades and come to the conclusion that the changes in the
population structure could not significantly influence the cancer mortality rate rise in the period
1985-2005.
4.2 Cancer incidence and mortality rates in Serbia, 2005
Table 1 illustrates the cancer incidence and mortality rates in Serbia in 2005. The 2005
cancer incidence rates were provided by unpublished preliminary data of the Vojvodina Cancer
Registry and published data of the Central Serbia Cancer Registry. The data presented in the Table
represent estimated incidence for the whole territory of Serbia.
16
Unpublished cancer mortality data have been taken over from the National Statistics Office
and processed at the Public Health Institute.
In addition to the overall cancer incidence and mortality rates in Serbia, selected
localizations are also presented with their pertinent incidence and mortality rates.
Table 1. Cancer incidence of and mortality rates in Serbia, 2005
Incidence* Mortality** Males Females Males Females
Cancer site ICD 10
Number of cases
Crude rate
Number of cases
Crude rate
Number of deaths
Crude rate
Number of deaths
Crude rate
Oral cavity C00-08 352 9.8 194 5.1 151 4.2 62 1.6 Pharynx C09-14 216 6.0 49 1.3 183 5.1 44 1.2 Esophagus C15 209 5.8 46 1.2 201 5.6 42 1.1 Stomach C16 746 20.7 468 12.3 744 20.6 463 12.1 Colon-rectum C18-21 2150 59.7 1514 39.8 1407 38.9 1079 28.2 Liver C22 351 9.7 228 6.0 428 11.8 304 8.0 Pancreas C25 424 11.8 397 10.4 518 14.3 470 12.3 Larynx C32 595 16.5 69 1.8 365 10.1 42 1.1 Lung C33-34 3876 107.6 1139 29.9 3522 97.3 1021 26.7 Melanoma C43 235 6.5 216 5.7 128 3.5 96 2.5 Non-melanoma skin cancer C44 1541 42.8 1460 38.3 81 2.2 70 1.8 Breast C50 110 3.1 3498 91.9 36 1.0 1569 41.0 Cervix uteri C53 - - 1236 32.5 - - 485 12.7 Corpus uteri C54 - - 832 21.8 - - 153 4.0 Ovary C56 - - 666 17.5 - - 369 9.7 Prostate C61 1420 39.4 - - 827 22.9 - - Kidney C64 353 9.8 219 5.8 195 5.4 130 3.4 Urinary bladder C67 942 26.1 314 8.2 394 10.9 125 3.3 Central nervous system C70-72 420 11.7 356 9.3 364 10.1 272 7.1 Hodgkin disease C81 137 3.8 112 2.9 43 1.2 32 0.8 Non-Hodgkin lymphoma C82-85. C96 313 8.7 235 6.2 139 3.8 129 3.4 Leukemia C91-95 340 9.4 242 6.4 306 8.5 191 5.0 Other 1481 41.1 804 21.1 1137 31.4 1424 37.3 All cancers 16211 449.8 14294 375.4 11169 308.7 8572 224.2
Crude rate per 100 000 person years * estimates: - sources: 1. preliminary data from Cancer Registry of Vojvodina, Oncology Institute of Vojvodina. (Author: Prof. Marica Miladinov-Mikov. MD.Ph.D) and 2. published data from Cancer Registry of Central Serbia, Institute of Public Health of Serbia **Source: unpublished data from Serbian National Statistics Office
17
References
Doll R. Peto R. The Causes of Cancer. Appendix C. Oxford University Press 1981. pp
1270–1281.
Boyle P. d’Onofrio A. Maisonneuve P. et al. Measuring progress against cancer in Europe:
has the 15% decline targeted for 2000 come about? Annals Oncol 2003;14:1312–1325.
Bray F. McCarron P. Parkin DM. The changing global patterns of female breast cancer
incidence and mortality. Breast Cancer Res 2004;6:229–239.
Ciccolallo L. Capocaccia R. Coleman MP. et al. Survival differences between European and
US patients with colorectal cancer: role of stage at diagnosis and surgery. Gut 2005;54:268–273.
Ferlay J. Autier P. Boniol M. Heanue M. Colombet M. Boyle P. Estimates of the cancer
incidence and mortality in Europe in 2006. Ann Oncol 2007;18:581–592.
Hill C. Benhamou E. Doyon F. Trends in cancer mortality. Lancet 1990;336:1262–1263.
Levi F. Lucchini F. Negri E. Boyle P. La Vecchia C. Cancer mortality in Europe. 1995–
1999. and an overview of trends since 1960. Int J Cancer 2004;110:155–169
Parkin. D.M.. Whelan. S.L.. Ferlay. J.. and Storm. H. Cancer Incidence in Five Continents.
Vol. I to VIII. IARC CancerBase No. 7. Lyon. 2005.
WHO Statistical Information System (WHOSIS). Mortality Database. Available from
http://www3.who.int/whosis/menu.cfm. accessed March 2006.
18
5. Burden of cancers attributable to certain risk factors, Serbia 2000
Table 2 shows ranks of 18 health disorders, by sex, based on u Disability Adjusted Life
Years (DALYs) from the 2000 Serbian Study of Burden of Diseases and Injuries. Results of the
study suggest that the total burdens of malignancies in men and women were 21.07%, and 22.03%,
respectively. In the total ranking of 18 selected diseases and injuries based on DALY in 2000 in
Serbia, lung cancer ranked 3, colon and rectum cancer 7, breast cancer 8, and stomach cancer 10.
The burden of cancer in men is predominated by lung cancer, which is followed by
colorectal cancer and stomach cancer. In our female population the cancer burden is predominated
by breast cancer, which is followed by lung cancer, colorectal cancer, cervical cancer and stomach
cancer (Table 2).
Table 2. Rankings of DALYs for 18 selected causes by gender, Serbia 2000.
Male Female Rank Cause %* Cause %* 1 Ischemic heart disease 27.64 Cerebrovascular disease (Stroke) 25.59 2 Cerebrovascular disease (Stroke) 18.94 Ischemic heart disease 19.98 3 Lung cancer 13.40 Unipolar depressive disorders 12.32 4 Road-traffic accidents 6.92 Breast cancer 8.57 5 Self-inflicted injuries 6.34 Diabetes mellitus 7.35 6 Unipolar depressive disorders 5.49 Lung cancer 4.57 7 Diabetes mellitus 4.93 Colorectal cancer 3.82 8 Colorectal cancer 4.47 Cervix uteri cancer 3.00 9 Stomach cancer 3.11 Nephritis and nephrosis 2.48 10 Birth asphyxia and birth trauma 2.33 Road-traffic accidents 2.34 11 Nephritis and nephrosis 2.14 Self-inflicted injuries 2.15 12 Asthma 2.11 Stomach cancer 2.07 13 Low birth weight 0.73 Asthma 2.06 14 Tuberculosis 0.70 Birth asphyxia and birth trauma 1.98 15 HIV/AIDS 0.35 Low birth weight 0.82 16 Vision and Hearing Loss 0.30 Vision and Hearing Loss 0.43 17 Breast cancer 0.09 Tuberculosis 0.29 18 - - HIV/AIDS 0.19 * % of Total DALYs for selected 18 causes
The total burden of selected malignancies attributable to smoking, alcohol, physical
inactivity and obesity is presented in Table 3. Results of the study suggest that smoking accounted
for 84.3% of the lung cancer burden and 9.58% of the cervical cancer burden. Physical inactivity
accounted for 26.0% of the lung cancer burden and 15.1% of the breast cancer burden. Results of
19
the same study also indicated that obesity was responsible for 14.4% of the colorectal cancer burden
and 6.4% of the breast cancer burden, while alcohol drinking accounted for 8.5% of the breast
cancer burden.
Table 3. Total burden of selected cancers attributable to risk factors (in percents), Serbia, 2000.
Conditions
Risk factors
% of total DALYs attributable to risk factors
Cancers Lung cancer
Tobacco
84.30
Cervix uteri cancer Tobacco 9.58 Breast cancer Alcohol (harm)
Physical inactivity Obesity
8.47 15.13 6.38
Colon and rectum cancers
Physical inactivity Obesity
25.96 14.38
References Atanasković-Marković Z, Bjegović V, Janković S, Kocev N, Laaser U, Marinković J, et al.
The Burden of Disease and Injury in Serbia. Belgrade: Ministry of Health of the Republic of Serbia;
2003.
International Agency for Research on Cancer. IARC. Monographs on the Evaluation of
Carcinogenic Risks to Humans. Vol 83. Tobacco Smoke and Involuntary Smoking. Lyon. IARC.
2004.
20
6. Selected cancer risk factors in Serbia
Smoking, excessive alcohol consumption, obesity, irregular diet and physical inactivity are
the leading risk factors in the Serbian population. The listed risk factors are common for numerous
chronic noncommunicable diseases which, in the light of their multifactorial etiology, are associated
with the presence of two or more of the se risk factors.
The results of the Serbian 2000 and 2006 Population Health Surveys relating to the
prevalence of risk factors attributable to cancer are presented in Table 4.
The 2006 Survey has shown that 33.6% of the adult population are smokers, 40.3% drink
alcohol every day or occasionally, 18.3% are obese and 59.9% are not sufficiently physically active
during leisure periods. In comparison with the previous, 2000 Survey, the 2006 adult Serbian
population shows reduction of the smoking prevalence by 6.9%, alcohol consumption by 7.2%.
The prevalence of obesity, however has risen by 1% and physical inactivity by 7.8% (Table 4).
Table 4. Prevalence of risk factors attributable to cancer in Serbia, for the years 2000 and 2006
Year Prevalence of risk factors (%) 2000 2006
Tobacco 40.5 33.6 Alcohol 47.5 40.3 Obesity 17.3 18.3
Physical inactivity 59.9 67.7
References
National Health Survey Serbia, 2000 – Institute of Public Healt of Serbia, 2000
National Health Survey Serbia – Key finding. Belgrade: Ministry of Health, Republic of
Serbia; 2006
21
6.1 Tobacco smoking
It has been estimated that almost 1.3 billion people smoke tobacco worldwide. The use of
tobacco, i.e. smoking, is not only a risk factor for the occurrence of malignant, pulmonary and
cardiovascular diseases, but tobacco addiction is a disease in itself. Tobacco smoking is directly
responsible for a half of fatal outcomes of chronic smokers globally. Every year, about five million
fatal outcomes worldwide are caused by tobacco use. Tobacco control is one of the most cost-
effective, evidence based health policies.
According to the National Cancer Institute, tobacco smoke may be related to 30% of all
cancer deaths and 87% lung cancer deaths in the USA.
It has also been confirmed that exposure to passive smoking is an important carcinogenic
factor for the occurrence of lung cancer (IARC. 2004).
The smoking prevalence in Serbia is high. According to the population health survey
conducted in 2000 covering the ages of 20 yrs and above, the male prevalence rate (48%) was
among the highest in Europe, while the female smoking prevalence was the highest in Europe
(33.6%).
The survey repeated in 2006 showed that 33.6% adults in Serbia (47.9% men and 33.7%
women) smoked tobacco daily or occasionally. In comparison to the previous, 2000 survey, the
tobacco smoking prevalence was reduced by 6.9% on the average, i.e. by 9.8% in men and by 3.8%
in women. In 2006 the daily smoking habit was present in 27.7% adults, indicating a 6.6%
reduction in comparison with 2000. Almost one in four women (23.7%) and one in three men
(32.5%) were classified as regular (daily) smokers. Out of these regular smokers 66.8% smoked
more than 20 cigarettes a day. The average “history of smoking” of these regular smokers was 18.8
years. In Serbia 5.9% population was classified as “occasional smokers”. In the same year 61.7% of
the population was exposed to smoke at their own homes, which is a 4% reduction in comparison
with 2000. On the other hand, 44.9% population in 2006 were still exposed to smoke at their place
of work in spite of the adopted Law on Prohibition of Smoking Indoors. Although the exposure to
smoke at workplace is reduced by somewhat over 10% in comparison with 2000, the information
should be taken with a grain of salt, because of rising unemployment in Serbia.
According to the global smoking survey among the young conducted in Serbia in 2003
among 13–15 year old students, the prevalence of smoking among them is also very high:
• 54.7% of the young aged 13–15 tried smoking a cigarette at least once;
• 16.8% girls and 15.5% boys smoked regularly (daily);
22
• 97.4% of the young were exposed to second-hand smoke at home and 91.3% at public
places.
The fall of smoking prevalence among the population of Serbia after 2000 resulted from a
continuous anti-smoking campaign on the national level. Laws on prohibition of sales of cigarettes
to under-age individuals and prohibition of smoking g in public places were adopted, and in 2007
the Strategy and Convention of Smoking Control in Serbia were adopted, as well.
6.1.1 Definition of exposure
Tobacco smoking causes cancer of the oral cavity, pharynx, esophagus, stomach, nasal
cavity and sinuses, upper trachea, lungs, kidneys, urinary bladder, uterine cervix, and acute myeloid
leukemia (IARC. 2004).
All forms of tobacco cause cancer. The greatest cancer risk is due to cigarette smoking since
cigarette smoke is usually inhaled, but cigars and pipes may be associated with the same risk if the
smoke is inhaled. The risk of malignancy is lower in former than in current smokers. Beneficial
effect of quitting is evidenced already after five years, and it is progressively increased over time.
For the purpose of the study we considered regular smoking of any tobacco product
(smokeless tobacco products are not used in Serbia). We divided smokers in respect to their
smoking history to the current and former smokers. We disregarded duration of smoking and
amount of tobacco smoked.
6.1.2 Relative risks (RR) for malignancies in smokers
The relative risks for malignancies that were used for the calculation of attributive fraction
have been taken over from IARC and presented in Table 8.
23
Table 8 Relative risks (RR) of cancer of specific organs associated with tobacco smoking, by sex*
* From meta analysis of studies reported in the IARC monograph on tobacco (2004) and Gandini et al. (2007) § RRs for former smokers among women were estimated using the rat o of ln (RR current smoker) to ln (RR former smoker) among men that we applied to ln (RR current smoker) for women. † When RRs for women were higher than for men or when no RR was estimable for women. the RR for men was used instead ‡ For cervix uteri the ratio ln(RR current)/ln(RR former) and the variance used were the average of those of all other sites 6.1.3 Data on exposure prevalence
In the light of the fact that the latency period for malignancies ranges 10-15 years, the best
thing to do was to use the data on smoking habits of the Serbian population in 1990. Since the data
was not available, the 1990 smoking prevalence was obtained by interpolation of the data on
smoking prevalence from the 2000 Serbian National Health Survey and Countrywide Integrated
Noncommunicable Diseases Intervention (CINDI) program conducted since 1985 on the territory of
Vojvodina (Table 9).
Table 9. Prevalence* of tobacco smoking in Serbia. by sex, 1985 and 2000 Year Prevalence* of tobacco smoking Smokers Ex-smokers
All 44.8 15.2 Male 56.2 21.3
1985θ
Female 33.8 8.4 All 40.5 13.8
Male 47.9 18.9 2000Ψ
Female 33.7 8.5 θ Countrywide Integrated Noncommunicable Diseases Intervention (CINDI), N. Sad, Serbia and Montenegro, 2003, population Ψ National Health Survey Serbia, Belgrade, Serbia, 2000
Men Women
Cancer site Current smoking
Former smoking
Current smoking
Former smoking
Oral cavity 4.22 1.57 160 1.16 Pharynx 6.82 2.28 3.29 1.67 Esophagus 2.52 2.13 2.28 1.96 Stomach 1.74 1.34 1.45 1.22 Liver 1.85 1.69 1.49 1.41 Pancreas 1.63 1.10 1.63† 1.10 Larynx 5.24 4.96 5.24† 4.96 Lung 9.87 3.18 7.58 2.78 Kidney 1.59 1.27 1.35 1.17 Urinary bladder 2.8 1.90 2.73 1.87 Cervix uteri – – 1.83 1.32‡
24
According to this estimate, in 1990 the prevalences of male and female smokers were 53.4%
and 33.8%, respectively, while there were 14.7% male and 8.4% female former smokers,
respectively (Table 10).
Table 10. Prevalence of tobacco smoking in Serbia, by sex, 1990 Prevalence* of tobacco smoking Smokers Ex-smokers
All 43.4 14.7 Male 53.4 20.5
Female 33.8 8.4 *estimates for 1990 obtained by linear interpolation of smoking prevalence data for 1985 and 2000.
6.1.4 AF estimates
Table 11 presents the AF values (calculated with the estimated 1990 prevalence), number of
new cancer cases and cancer deaths that may be attributed to smoking in Serbia in 2005. The total
of 5277 cancer cases among men (32.6% of total) and 1693 among women (11.8%) were
attributable to cigarette smoking. Among all cancer sites attributable to cigarette smoking in Serbia,
lung cancer was recorded in 61.5% men and 47.3% women.
Table 11. Numbers* of cancer cases and deaths attributable to tobacco smoking in Serbia, by sex, 2005
Men Women Cancer site AF% Cases Deaths AF% Cases Deaths Oral cavity 64.7 228 98 98.2 190 61 Pharynx 77.1 167 141 45.4 22 20 Esophagus 51.1 107 103 33.9 16 14 Stomach 31.7 237 236 14.6 68 67 Liver 37.3 131 160 16.7 38 51 Pancreas 26.3 112 136 18.1 72 85 Larynx 75.5 449 275 63.8 44 27 Lung 83.8 3249 2952 70.4 801 718 Kidney 27.0 95 53 11.7 26 15 Urinary bladder 53.4 503 210 39.7 125 50 Cervix uteri - - - 23.5 291 114 Total 5277 4365 1693 1222 % of all cancers 32.6% 39.1% 11.8% 14.3%
*based on the estimated 1990 cancer prevalence
25
Because of high lethality of many cancer sites attributable to tobacco smoking, the
corresponding figures for mortality are higher than for the incidence (39.1% of all cancer deaths in
men and 14.3% in women).
In the light of the fact that the 1985 smoking prevalence which was used for determination
of 1990 smoking prevalence was probably higher than the actual one, since it covered the 25-65 yr
population, the AFs were calculated for the 2000 smoking prevalence, as well (Table 12). The AFs,
calculated in this manner, suggest that 5124 cases of male cancer (31.6% of total) and 1691 cases of
female cancer (11.8%) were attributable to cigarette smoking. The share of lung cancer among all
cancer sites attributable to tobacco smoking was 62.3% in men and 47.4% in women. The
corresponding figures for cancer deaths were 38.0% and 14.2% in men and women, respectively.
Table 13. Numbers* of cancer cases and deaths attributable to tobacco smoking in Serbia, by sex, 2005
Men Women Cancer site AF% Cases Deaths AF% Cases Deaths Oral cavity 62.3 219 94 98.2 190 61
Pharynx 75.2 162 138 45.3 22 20
Esophagus 48.5 101 97 33.9 16 14
Stomach 29.5 220 220 14.6 68 67
Liver 35.0 123 150 16.7 38 51
Pancreas 24.3 103 126 18.1 72 85
Larynx 73.5 438 268 63.8 44 27
Lung 82.3 3191 2900 70.3 801 718
Kidney 25.0 88 49 11.7 26 15
Urinary bladder 50.8 478 200 39.6 124 50
Cervix uteri - - - 23.5 290 114
Total 5124 4241 1691 1221
% of all cancers 31.6% 38.0% 11.8% 14.2% *based on 2000 smoking prevalence
As expected, the obtained AF estimates, as well as numbers of new cancer cases and cancer
deaths attributable to cigarette smoking in Serbia (2005) were similar to the 1990 data obtained with
by linear interpolation and those on smoking prevalence obtained in the 2000 Serbian National
Health Survey (Tables 11 & 12).
26
Indirect AF assessment
The relative risks taken over from IARC publication were based on the results of meta
analysis comprising a large number of studies conducted in the USA or Nordic countries, so that
one may question whether the smoking habits of these population are comparable to the smoking
habits of Serbian population. Therefore, we applied an indirect AF assessment.
The results of indirect assessment for lung cancer AF (Peto et al.) are presented in Table 14.
The method is based on the assumption that since smoking is the main environmental risk factor for
lung cancer and since lung cancer is incurable, the lung cancer deaths are a better parameter of the
impact of smoking on the occurrence of this disease than the smoking prevalence itself.
Hypothetically, we assumed that no cases of lung cancer deaths were attributable to smoking
by 1950, and that any increase of lung cancer death after 1950 was attributable to tobacco smoking.
The following equation was used for the calculation:
AF = (2005 mortality rate – 1950 mortality rate) /2005 mortality rate
Age-related AF assessment was used for the number of deaths in 2005 for each age group
(Table 14). Out of 3522 lung cancer deaths of men registered in 2005 in Serbia, 3362 were
attributable to tobacco smoking, corresponding to AF of 95.5%; out of 1021 lung cancer deaths of
women registered in Serbia in the same year, 953 were attributable to tobacco smoking,
corresponding to AF of 93.3% (Table 14).
27
Table 14. Fractions (AF*) of lung cancer attributable to tobacco smoking in Serbian men and women 2005, calculated by the indirect method Men
*AF for all ages estimated after calculation of AFs for each age category and application of age-specific AFs to the numbers of lung cancer deaths observed in each age category in 2005. Source: unpublished death data from National Statistics Office of Serbia and census data of population in FNRY, 1950 Women
*AF for all ages estimated after calculation of AFs for each age group and application of age-specific AFs to the numbers of lung cancer deaths observed in each age group in 2005. Source: unpublished death data from National Statistics Office of Serbia and census data of population in FNRY, 1950
6.1.4 Discussion Our analysis has shown that tobacco smoking is the main avoidable cause of cancer among
both men and women. The impact of tobacco as the risk factor would have been even higher if the
calculations had included some rare types of cancer (nasopharyngeal cancer, cancer of the nose and
paranasal sinuses, myeloid leukemia) where causative relation with tobacco smoking was evidenced
(IARC, 2004), as well as some other types of cancer (colorectal cancer) that are suspected of having
the causative relation with tobacco smoking, but without sufficient evidence for such an claim.
It is questionable to what extent the data on 1990 smoking prevalence obtained by
interpolation are accurate. However, it is the fact that no major differences in AF calculated with
estimated 1990 smoking prevalence and AF calculated with smoking prevalence in 2000, provided
from the „Population Health Survey in Serbia“, have been observed. There is also an issue of
Age group Mortality rate in 1950 * Mortality rate in 2005 AF (%) 0 – 29 0.05 0.15 66.7 30 – 39 0.78 4.34 82.0 40 – 49 2.44 42.37 94.2 50 – 59 8.46 171.94 95.1 60 – 69 17.04 304.74 94.4
70 + 9.72 354.98 97.3 All 72.9
Age group Mortality rate in 1950 * Mortality rate in 2005 AF (%) 0 – 29 0.00 0.00 0.0 30 – 39 0.48 2.47 80.5 40 – 49 0.73 13.77 94.7 50 – 59 2.72 46.46 94.1 60 – 69 6.50 56.51 88.5
70 + 3.54 84.95 95.8 All 93.3
28
whether the relative risks used for AF calculations, taken over from other populations do
correspond to RRs for the Serbian population.
Nevertheless, even if the number of cancer cases and cancer deaths attributable to smoking
would turn out to be lower than the ones calculated in this study, tobacco smoking would still
remain the main avoidable cause of cancer.
In the light of the high prevalence of smoking among the Serbian population in 2000, it may
be assumed that the incidence of malignancies related to smoking will be still high in the following
15-20 years. Only after that, the positive effect of reduced smoking prevalence recorded in the
period 2000-2006 could become noticeable, under the condition that the trend is maintained.
References
http://data.euro.who.int/tobacco/
www.heartstats.org
Attributable causes of cancer in France in the year 2000, IARC Working Group Reports
Vol. 3, International Agency for Research on Cancer, 2007
The Republic of Serbia strategy for the prevention and control of noncommunicable
diseases of the Republic of Serbia. Ministry of Health of the Republic of Serbia. NCD Committee,
Belgrade, 2008
Global Youth Tobacco Survey. UNICEF. Ministry of Health of the Republic of Serbia,
2003
Zdravstveno stanje stanovništva Srbije 2000. godine, Beograd, 2003
National Health Survey Serbia – Key finding. Belgrade: Ministry of Health, Republic of
Serbia; 2006
Šaulić A. Atanasković-Marković Z. Burden attributable to major risk factors. In:
Atanasković Marković Z. Bjegović V. Janković S et al. The Burden of Disease and Injury in Serbia.
Belgrade: Ministry of Health of the Republic of Serbia; 2003.
http://www.european-lung-foundation.org/
Tobacco Smoke and Involuntary Smoking, IARC monographs on the Evaluation of
Carcinogenic Risks to Humans, WHO, IARC vol. 83, 2004
Smokeless Tobacco and Some Tobacco-specific N-NitrosaminesSmokeless tobacco, IARC
monographs volume 89, 2006
National Center for Health Statistics. Health, United States, 2003 (NHIS Data)
29
Mackay J, Eriksen M. The Tobacco Atlas. 2002. WHO, Geneva
Helakorpi S, Patja K, Prattala R, Aro AR, Uutela A. Health behaviour and health among
Finnish adult populations, Spring 2003
U.S. Centers for Disease Control and Prevention, Web: www.cdc.gov.
Factsheet 98/2, Lung & Asthma Information Agency, Dept of Public Health Sciences, St.
George's Hospital Medical School, Cranmer Terrace, London, ww.laia.ac.uk/factsheets/982.pdf
WHO European Country Profiles on Tobacco Control 2003
30
6.2 Alcohol drinking
Alcohol drinking is an important health and social problem.
Pursuant to the 2006 National Health Survey in Serbia, 40.3% of the population drink
alcohol every day or occasionally, which is a 7.2% decrease from the 2000 Survey (Table 4). In
total, 3.4% of the population, i.e. 7.2% men and 0.4% women drank alcohol regularly, every day.
Among the regular drinkers more were ≥ 55 years old (16.5%) than below 55 yrs (7.0%). Strong
spirits, followed by beer were the favorites among the regular drinkers
Alcohol drinking is associated with a series of health disorders. This report focuses only
carcinogenic effects of alcohol consumption. Type of alcoholic beverage and frequency of
consumption (regularly/occasionally) were disregarded.
6.2.1 Relative risks (RR) for malignant tumors associated with alcohol consumption
Relative risks (RR) for malignant tumors used for the calculation of attributive function are
taken over from IARC publication and presented in Table 11.
6.2.2 Information used for exposure prevalence Taking into account that self-reported data on alcohol consumption are likely to be
underestimated, data from the National Statistics Office on food and beverages consumed in
Serbian households were used for estimation of alcohol intake. The year 1992 is the first year for
which such data was available.
Intake of ethanol for adult persons (15 years of age and above) in grams per day is used as
the measure of alcoholic beverage consumption (christianparty.net/globalalcoholeuro.pdf).
According to the 1992 data provided by the National Statistics Office (former Federal Republic of
Yugoslavia, subsequently Serbia and Montenegro) 9 liters of pure alcohol were consumed per
person per year, i.e. 19.45 grams of ethanol per person per day.
Since the data on alcohol intake from this study were not distributed by the sex, we used the
results published by Institut Nationale de la Statistique et des Etudes Economiques (INSEE,
France's National Statistical Office), suggesting that men drank 4.33 times more than women. Using
that ratio, the average daily doses of alcohol drank in 1992 were 31.6 grams and 7.2 grams for men
and women, respectively.
In the calculation of alcohol intake by the sex, we took into account the difference in size
between male and female populations (male/female =1.00/0.94).
31
6.2.3 AF Estimates According to the calculated AF values 719 cancer cases in men (4.4% of the total number of
men affected by malignancies) and 236 cancer cases in women (1.7%) are attributable to alcohol
intake. Out of all sites of cancer attributable to alcohol intake in Serbia, oropharyngeal cancer was
most common in men (37.0%) and breast cancer (71.2%) in women. Corresponding figures for the
deceased were 4.5% of all cancer deaths in men and 1.4% in women (Table 12).
According to the available data, alcohol drinking has significantly increased in Serbia over
the last 16 years, rising from 19.5 g in 1992 to 56.3 g in 2007.
Table 11. Relative risks for alcohol drinking and attributabl e fractions, by sex
RR for average consumption#
AF% Cancer Ln (risk per g/d)
Male Female Male Female Oral cavity, pharynx 0.020* 1.88 1.16 46.8 13.8 Esophagus 0.013* 1.51 1.10 33.8 9.1 Colorectal 0.002* 1.07 1.01 7.49 1.0 Liver 0.006* 1.21 1.04 17.4 3.8 Larynx 0.014* 1.37 1.11 27.0 9.9 Breast 0.007† - 1.05 - 4.8 # Men: 31.6 g/d ; women: 7.3 g/d (1992)
* Based on linear extrapolation from results of meta-analysis (Corrao et al.. 2004)
† Based on results of pooled analysis (Hamajima et al.. 2002)
Table 12. Number of cancer cases of and deaths attributable to alcohol drinking in Serbia in 2005, by sex
Incident cases Deaths Cancer Male Female Male Female Oral cavity, pharynx 266 34 156 15 Esophagus 71 4 68 4 Colorectal 161 15 105 11 Liver 61 9 74 12 Larynx 161 7 99 4 Breast - 168 - 75 Total 719 236 503 120 % total cancer cases/deaths 4.4% 1.7% 4.5% 1.4%
32
Due to increase in alcohol consumption in the studied period in Serbia, we calculated AFs
for alcohol intake in 1996 (10 year latency period) when 13.0 liters of pure alcohol was consumed
per person per year. According to the previously established ratio between the sexes, the amount
corresponded to the average alcohol intake of 45.6g in men and 10.5 in women. The AF values
calculated by the sex, attributable to alcohol intake are presented in Table 13. The AF values
calculated in this manner yield the 6.0% share of cancer cases attributable to alcohol drinking in
men and 2.5% in women. The corresponding shares of cancer deaths were 6.1% and 2.2% for men
and women, respectively (Table 14).
Table 13. Relative risks for alcohol drinking and attributabl e fractions, by sex
RR for average consumption#
AF% Cancer Ln (risk per g/d)
Male Female Male Female Oral cavity, pharynx 0.020* 2.48 1.23 59.7 18.7 Esophagus 0.013* 1.81 1.15 44.7 13.0 Colorectal 0.002* 1.09 1.02 8.3 2.0 Liver 0.006* 1.31 1.06 23.7 5.7 Larynx 0.014* 1.89 1.16 47.1 13.8 Breast 0.007† - 1.08 - 7.4 # Men: 45.6 g/d ; women: 10.5 g/d (1996)
* Based on linear extrapolation from results of meta-analysis (Corrao et al.. 2004)
† Based on results of pooled analysis (Hamajima et al.. 2002)
Table 14. Number of cancer cases of and deaths attributable to alcohol drinking in Serbia in 2005, by sex
Incident cases Deaths Cancer Male Female Male Female Oral cavity, pharynx 339 45 199 20 Esophagus 93 6 90 5 Colorectal 178 30 117 22 Liver 83 13 101 17 Larynx 280 10 172 6 Breast - 259 - 116 Total 973 363 679 186 % total cancer cases/deaths 6.0% 2.5% 6.1% 2.2%
33
6.2.4 Discussion Our estimates of the numbers of new cancer cases and cancer deaths attributable to alcohol
drinking were lower for men and approximately the same for women, when compared to results of
similar studies in Europe (Rehm et. al., 2003; Boffetta and Hashibe, 2006). After tobacco smoking,
alcohol drinking is the second leading avoidable cause of cancer in men in Serbia.
However, reliability of our estimates is limited by the quality of available information on
alcohol consumption in Serbia, as well as the use of relative risks from other population and
extrapolation of male/female ratio in alcohol consumption from other populations).
References
Ministry of Health of Serbia, National Health Survey Serbia, 2006
Boffetta P, Hashibe M. Alcohol and cancer. Lancet Oncol 2006;7:149–156.
Corrao G, Bagnardi V, Zambon A, La Vecchia C. A. meta-analysis of alcohol consumption
and the risk of 15 diseases. Prev Med 2004;38:613–619.
Hamajima N, Hirose K, Tajima K, et al. Alcohol, tobacco and breast cancer – Collaborative
reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast
cancer and 95,067 women without the disease. Br J Cancer 2002;87:1234–1245.
International Agency for Research on Cancer. IARC. Monographs on the Evaluation of
Carcinogenic Risks to Humans. Vol 96, Alcoholic Beverage Consumption. Lyon, IARC, 2007
http://www.christianparty.net/globalalcoholeuro.pdf
Rehm J, Gmel G, Sempos CT, Trevisan M. Alcohol related morbidity and mortality.
Alcohol Res Health 2003; 27:39–51.
34
6.3 Overweight and obesity
Obesity is a disease characterized with increased body mass to a degree that leads to health
problems and development of a series of complications. Obesity is the most common dietary
problem in developed countries and emerging problem in the developing ones. In addition to being
a disease in itself, obesity may be associated with the occurrence and course of many diseases such
as type 2 diabetes and reduced tolerance to glucose, cardiovascular diseases, cholelithiasis,
arthrosis, some malignant tumors, etc.
The body mass index is a widely accepted index to categorize levels of obesity in adults,
children and adolescents alike. The body mass index (BMI) is an anthropometric index defined as
body mass in kilograms divided by the height expressed in square meters.
Pursuant to international standards, men and women with BMI between 25 and 29.9 kg/m2
are classified as overweight persons, while those with body mass higher or equal to 30 are
considered obese. Results of the 2006 Health Survey in Serbia suggest that 38.3% have normal
body weight, 36.2% are overweight and 18.3% obese. There were 2.3% undernourished, as well
(Table 15).
The greatest percentage of overweight people is between 55 to 74 years of age. Pre-obesity
was more prevalent in men and persons aged 45 to 74 years.
In comparison with the previous, 2000 Health Survey in Serbia, in 2006 the incidence of
obesity has risen by 1%, while pre-obesity fell by 0.4% 0.4% u 2006 (Table 15).
Table 15. Prevalence of overweight and besity in Serbia in 2000 and 2006
Year Prevalence (%) of nutritional status (BMI) 2000 2006
Overweight (25.0-29.9 kg/m2) 36.6 36.2 Obesity (≥ 30.0 kg/m2) 17.3 18.3
*Source data: National Health Survey Serbia, Ministry of Health Republic of Serbia, Institute of Public Health of Serbia, Belgrade, 2000 and 2006
Results of a great number of studies suggest that overweight and obesity are linked to the
occurrence of cancer of esophagus, colorectal cancer, kidney cancer, uterine cancer and breast
cancer in post-menopausal women (IARC, 2002).
35
6.3.1 Relative risks (RR) for malignancies associated with overweight and obesity
Relative risks for the occurrence of malignant tumors that we used for the calculation of
attributive fractions were taken over from IARC (IARC, 2002 and Bergstrom et al., 2001). These
relative risks may be used in men and women, alike.
Table 16. Summary RRs of cancers associated with overweight and obesity
Cancer site Ψ Overweight Obesity* Esophagus (adenocarcinoma) 2.00 2.00 Colon-rectum 1.15 1.33 Kidney 1.36 1.84 Corpus uteri 1.59 2.52 Breast in postmenopausal women 1.12 1.25 * From Bergstrom et al., 2001 Ψ From IARC, 2002.
6.3.2 Information used for exposure prevalence
In the light of the fact that latency period for the occurrence of malignant tumors ranges 10-
15 years, it would be best to use the data on overweight and obesity of the Serbian population in
1990. Since there was no reliable data on the prevalence of obesity in 1990 or any of the years close
to it, we used the data on the prevalence of overweight and obesity collected in the 2000 National
Health Survey. The used data on the prevalence of overweight and obesity related to the adult
population (20 yrs and over).
The 2000 data on the prevalence of overweight and obesity by the sex in 2000 are presented
in Table 17.
Table 17. Prevalence of overweight and obesity in Serbia in 2000, by sex
BMI category Males Females
Overweight (25.0-29.9 kg/m2) 43.0 30.9 (39.5)* Obesity (≥ 30.0 kg/m2) 14.4 20.0 (29.4)*
* Only for women ≥ 50 years old
36
6.3.3 AF evaluation
Table 18 shows the list of AF values (calculated with the prevalence of overweight and
obesity in 2000), number of new cancer cases and cancer deaths that are attributable to overweight
and obesity in Serbia in 2005. The total of 306 cases of cancer in men (1.9% of the total number of
cancer cases) and 776 new cancer cases in women (5.4%) are attributable to overweight and
obesity. Out of all cancer sites related to BMI≥25.0, the share of colorectal cancer in men (70.9%)
and breast cancer in women (37.4%) were the greatest.
The corresponding values for cancer deaths were 1.7% and 4.0% in men and women,
respectively (Table 18).
Table 18. Number of cancer cases and deaths attributable to obesity and overweight in Serbia in 2005
Men Women Cancer
AF% Cases Deaths AF% Cases Deaths Esophagus (adenocarcinoma) 36.5 13 9 33.7 13 4 Colon-rectum 10.1 217 142 10.1 153 109 Kidney 21.6 76 42 21.8 48 28 Corpus uteri - - - 32.7 272 50 Breast over 50 years - - - 10.8 290 148 Total 306 193 776 340 % of all cancers 1.9% 1.7% 5.4% 4.0%
The number of cases of esophageal adenocarcinoma was taken over from Cancer Incidence
in Five Continents, Vol. IX, 2007, stating that this type of malignancy accounts for 16.8% and
19.4% of all esophageal malignancies in men and women, respectively.
6.3.4 Discussion
The data on body weight and height of the nation were obtained in the 200 National Health
Survey in Serbia following the standardized WHO methodology. It, however, remains questionable
whether the relative risks used for the AF calculation taken over from other populations, do
correspond to the RR in the Serbian population.
In most developed countries worldwide, overweight ad obesity are on the rise, which will
probably contribute to the increase incidence of some types of cancer in the future. In the light of
high prevalence of overweight ad obesity, as well as increased obesity in the period 2000-2006, the
similar situation may be expected in Serbia, as well.
37
References
CDC Growth Charts 2000. National Center for Hronic Disease Prevention and Health
Promotion. Division of Nutrition and Physical Activity. Maternal and Child Nutrition Brunch, june
2002. (cited, 2007, April 05)
Gojaznost – Nacionalni vodič za lekare u primarnoj zdravstvenoj zaštiti. Republička stručna
komisija za izradu i implementaciju vodiča u kliničkoj praksi. Ministarastvo zdravlja Republike
Srbije, novembar 2004
Bergstrom A, Pisani P, Tenet V, et al. Overweight as an avoidable cause of cancer in
Europe. Int J Cancer. 2001;91:421–30. Erratum in: Int J Cancer 2001;92:927.
International Agency for Research on Cancer. IARC Handbooks of Cancer Prevention, Vol.
5, Weight Control and Physical Activity. Lyon: IARC; 2002
Curado. M. P., Edwards, B., Shin. H.R., Storm. H., Ferlay. J., Heanue. M. and Boyle. P., eds
(2007) Cancer Incidence in Five Continents, Vol. IX IARC Scientific Publications No. 160, Lyon,
IARC.
38
6.4 Physical inactivity
Physical inactivity is an important criterion for evaluation of health and it is also a
significant risk factor for the occurrence of various diseases.
Events on preventive impact of physical inactivity on the occurrence of malignant diseases
have been presented in an IARC publication (IARC, 2002). The impact is particularly associated
with breast and colon cancers, increasing over time with decreasing physical activity.
So far, not a single study has been able to estimate the optimum level of physical activity to
prevent cancer. However, the IARC working group on physical inactivity has concluded that when
colon cancer is concerned “it is necessary to pursue at least 30 minutes a day more than the average
level of physical activity to notice marked effects on risk reduction” (IARC, 2002). The same
working group has noted that in most women reduction of the breast cancer risk “begins on the
level of 30-60 minutes daily physical activity of moderate to high intensity, as an addition to the
usual working activities” (IARC, 2002). According to the above, one may assume that lower or
moderate physical activity does not reduce the risk of breast or colon cancer.
According to the results of the National Health Survey in Serbia (2006) over two thirds
(67.7%) of adult population in Serbia spent their free time in a sedentary manner. The same survey
shows that 31.1% of our population pursues sedentary professions. Women, in comparison with
men, were much less active at work and during leisure alike. In comparison with the previous 2000
Survey, the latest one (2006) shows that the share of adults who spend their free time in a physically
inactive manner has been increased by 8%.
6.4.1 Relative risks (RR) for malignant tumors attributable to physical inactivity Relative risks for malignant tumors attributable to physical inactivity have been taken over
from IARC publication on the basis of meta analysis (Samad et al. 2005) – for colon cancer and
E3N cohort study conducted in France (Tehard et al., 2006) as well as a European study (Vaz de
Almeida et al. 1999) – for breast cancer.
6.4.2 Information used for exposure prevalence
The study uses the data on physical inactivity prevalence obtained in the 2000 Population
Health Survey conducted in Serbia. The data on the prevalence of physical inactivity are related to
adults (20 years and older).
39
Results of the stated study have shown that 41.3% men and 51.1% women do not pursue
any form of physical activity in their free time, and that additional 10.7% of men and 16.0% women
are prevented by disease/disability from doing so. Accordingly, the total of 52.0% men and 67.1%
women spend their leisure time in a predominantly sedentary manner.
Table 19 illustrates the prevalence of physical inactivity with associated relative risks used
in the AF evaluation.
Table 19. Prevalence of physical inactivity in Serbia adults and associated RR Cancer Sex % inactivity RR* 95% CI
Men 52.0% 1.27 1.10 1.47 Colon-rectumθ Women 67.1% 1.40 1.13 1.74
Breast* Women 67.1% 1.32 1.06 1.64 θ Samad et al. 2005
* Tehard et al., 2006; Vaz de Almeida et al. 1999
6.4.3 AF Estimates
Table 20 illustrated the AF values for new cancer cases and cancer deaths in 2005 that may
be attributable to physical inactivity. In 2005 in Serbia, 264 new colon cancer cases in men (1.6% of
all new cancer cases) and 940 new colon and breast cancer cases in women (6.6% of the total
number of new cancer cases) may be attributed to physical inactivity. Physical inactivity is also
associated with 174 colon cancer deaths in men (1.6% of all cancer deaths) and 507 cancer deaths
(colon and breast cancer combined) in women (5.9% of all cancer deaths).
Table 20. Numbers of cancer cases and deaths attributable to lack of physical activity in Serbia, by sex, for the year 2005
Men Women Cancer AF% Cases Deaths AF% Cases Deaths
Colon-rectum 12.3% 264 174 21.2% 321 229 Breast - - - 17.7% 619 278
Total - 264 174 - 940 507
% all cancer - 1.6% 1.6% - 6.6% 5.9%
40
6.4.4 Discussion
A large part of adult population of Serbia spend their free time in sedentary activities.
Results of the 2000 National Health Survey show that 59.9% of adult population of Serbia are not
physically active in their free time.
The prevalence of physical inactivity reported in health surveys in Serbia is high in
comparison with other European countries (Tehard et al., 2006) suggesting the need for direct
promotion of physical activity for prevention of some malignant tumors and other health disorders.
References
International Agency for Reasearch on Cancer. IARC Handbooks of Cancer Prevention,
Vol. 5, Weight Control and Physical Activity. Lyon: IARC; 2002.
Tehard B, Friedenreich CM, Oppert JM, Clavel-Chapelon F. Effect of physical activity on
women at increased risk of breast cancer: results from the E3N cohort study. Cancer Epidemiol
Biomarkers Prev 2006;15:57–64.
Vaz de Almeida MD, Graca P, Afonso C, et al. Physical activity levels and body weight in a
nationally representative sample in the European Union. Public Health Nutrition, 1999; 2(1a): 105–
113.
Samad AKA, Taylor RS, Marshall T, Chapman MAS. A meta-analysis of the association of
physical activity with reduced risk of colorectal cancer. Colorectal Disease 2005;7:204–213.
41
6.5 Chronic infections Chronic infections caused by viruses, bacteria and parasites are risk factors for many
malignant tumors. Estimates based on laboratory studies and epidemiological data suggest that 10 to
15% of malignancies may be related to infectious agents, out of which hepatitis B and C, human
papilloma virus and Helicobacter pylori account for a third. According to Pisani et al. it was
estimated that chronic infections were accountable for 9% of cancer cases in 1990, while Hausen
reports that 20% malignancies could be associated with an infective agent. Evaluation of the
strength of the causative association between an infection and the occurrence of a malignancy is
primarily limited by scarce possibilities in the use of markers of previous exposure to viral
infections so that the evaluation of the causal relationship is mainly based on historical studies,
while cohort studies are quite rare.
IARC monographs illustrate the already established association of infections and cancer:
Epstein-Barr virus (EBV) and Hodgkin’s, non-Hodgkin’s lymphoma and nasopharyngeal cancer;
Human immunodeficiency virus (HIV) and non-Hodgkin’s lymphoma and Kaposi’s sarcoma;
Human papilloma virusa (HPV) and cervical cancer, oropharyngeal cancer, cancer of the anus,
penis, vulva and vagina; Hepatitis B and C viruses (HBV and HCV) and liver cancer; bacterium
Helicobacter pylori and stomach cancer; and parasite Shistosoma haematobium and urinary bladder
cancer, and Opistirchis viverini and liver cancer.
In our report we calculated AF for cervical cancer, oropharyngeal cancer, liver cancer,
Hodgkin’s and non-Hodgkin’s lymphoma and stomach cancer.
6.5.1 Relative risks (RR) for malignant tumors due to exposure
Relative risks for the occurrence of malignancies that were used for attributive fraction
calculations were taken over from IARC publication and presented in Table 21.
Table 21. RRs and prevalence of exposure to infectious agents used in the calculation of AFs
Prevalence of infection, % Agent Cancer RR Men Women
EBV Hodgkin lymphoma - 20.01 20.01 EBV non- Hodgkin lymphoma - 20.01 20.01 HBV Liver cancer 18.8 0.97 0.13 HCV Liver cancer 31.2 0.63 0.85 HPV Cervical cancer - 15.5* 15.5* HPV Oropharyngeal cancer 2.1 6.5 6.5 H. Pylori Stomach cancer 2.04 25.0 25.0 *Not used for AF calculation, that is assumed to be 100%
42
6.5.2 Information used for exposure prevalence
The data on the prevalence of exposure to infectious agents is presented in Table 21.
Prevalence of HBV and HCV infections among the adult population of Serbia was derived
from extrapolated evaluations of prevalence for Serbia and Montenegro
(http://www.wrongdiagnosis.com, 2008) and reports on tested blood donors on the territory of
Belgrade in 2007 (Serbian Institute of Transfusion, 2008).
HPV prevalence in anogenital tract was based on examinations of women in Belgrade
(Knežević A, 2008) and Vojvodina (Miladinov-Mikov M, 2008). The same value of HPV
prevalence was used for men, as well. Prevalence of HPV in the oral cavity was taken from the
IARC publication. The same HPV prevalence value was used for men and women.
Prevalence of H. pylori infection was derived from the estimates for developing countries
(Pounder RE, Ng D, 1995). The same prevalence value was applied for adults of both sexes
In absence of the historical data on the infections we assumed that the prevalence of the
infections has not changed over time.
6.5.3 AF calculations
Table 22 illustrates the AF values, number of new cancer cases and cancer deaths that are
attributable to infectious agents we studied in 2005. AF 40% for Hodgkin’s lymphoma and 8% for
non-Hodgkin’s lymphoma were taken over from the IARC publication.
The total of 379 male cancer patients (2.3% of the total number of new cases) and 1464
women with malignancies (10.2% of the total number of new cases) are attributable to infections in
Serbia in 2005. Liver cancer resulting from HBV and HCV infections in Serbia account for
approximately one quarter of new cases of malignancies in men that are attributable to infections.
As many as 85% of new cases of cervical cancer in Serbia are attributable to HPV infection (Table
22).
43
Table 22. Number of cancer cases and deaths attributable to chronic infection in Serbia by sex, for the year 2005
6.5.4 Discussion The fact that relative risks for cancer attributable to exposure to infectious agents are taken
over from other populations, that the prevalence data are based on results of the studies conducted
in some segments of the population only, and in the period after the occurrence of malignancies
(2006 and 2007) make the evaluation of the numbers defining morbidity and mortality attributable
to infectious agents less valid.
Differences between theses estimates and the estimates yielded by other authors may have
been influences by RR, exposure prevalence and, undoubtedly, the methodology applied for
prevalence evaluation, as well. The prevalence estimates based on expert opinions, environmental
data or models (model approaches) used in some studies are usually overrated. The total number of
new cancer cases and cancer deaths attributable to infectious agents may be influenced by the
number of malignancies covered by the study. We did not calculate AFs for non-Hodgkin’s
lymphoma and Kaposi’s sarcoma that are attributable to HIV infection since we do not have reliable
data on HIV infection prevalence in the Serbian population.
References
Pisani P, Parkin DM, munoz N et al. Cancer and infection: estimates of the attributable
fraction in 1990. Cancer epidemiologz, Biomarkers and Prevention 1997; 6: 387-400
Men Women Cancer Agent AF % Cases Deaths AF % Cases Deaths
Hodgkin lymphoma EBV 40.0% 55 17 40.0% 45 13 Non-Hodgkin lymphoma EBV 8.0% 25 11 8.0% 19 10 Liver HCV 16.0% 56 68 20.4 47 62 Liver HBV 14.7% 52 63 2.3 5 7 Oral cavity and pharynx HPV 6.7% 38 22 6.7 16 7 Cervix uteri HPV - - - 100% 1236 485 Stomach H. pylori 20.6% 154 32 20.6 97 96 Total 379 214 1464 680 % all cancers 2.3% 1.9% 10.2% 7.9%
44
Clavel C, Cucherousset J, Lorenzato M, et al. Negative human papillomavirus testing in
normal smears selects a population at low risk for developing high-grade cervical lesions. Br J
Cancer 2004;90:1606–1609.
Donato F, Boffetta P, Puoti M. A meta-analysis of epidemiological studies on the combined
effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. Int J Cancer
1998;75:347–354
International Agency for Research on Cancer. Hepatitis B virus. IARC Monographs on the
Evaluation of Carcinogenic Risks to Humans, Vol. 59, Hepatitis Viruses. IARC, Lyon, 1994a, pp.
45–164
International Agency for Research on Cancer. Hepatitis C virus. IARC Monographs on the
Evaluation of Carcinogenic Risks to Humans, Vol. 59. Hepatitis Viruses. IARC, Lyon, 1994b,
pp. 165–221.
International Agency for Research on Cancer. Infection with Helicobacter pylori. IARC
Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 61.
International Agency for Research on Cancer. Human Papillomaviruses. IARC Monographs
on the Evaluation of Carcinogenic Risks to Humans, Volume 90. Lyon, IARC, 2006
http://www.wrongdiagnosis.com/h/hepatitis_b/stats-country.htm
Marica Otašević, Aleksandar Nagorni, Dobrila stanković-ðorñević,Marina Dinić, Ljiljana
Otašević, Helicobacter pylori and gastric cancer, Archive of Oncology 2003;11(4):233-7.
Aleksandra Knežević. Molekularna analiza HPV izolata sa grlića materice žena u
reproduktivnom periodu, Medicinski fakultet Univerziteta u Beogradu, Beograd, 2008
Pounder RE, Ng D. The prevalence of Helicobacter pylori infection in different countries.
Aliment Pharmacol Ther. 1995;9 Suppl 2:33-9.
Mladen Davidovic, Petar Svorcan, Pavle Milanovic, Aleksandr Antovic, Dragoslav
Milosevic, Specifics of Helicobacter pylori Infection/NSAID Effects in the Elderly, Romanian
Journal of Gastroenterology September 2005 Vol.14 No.3, 253-258
45
6.6 Use of oral contraceptives
Oral contraceptives (OC) are classified as class carcinogenic agents (Cogliano et al., 2005).
It has been estimated that one in ten women in the reproductive age uses combined hormonal
contraceptives. They are most commonly used as oral preparations. The use of oral contraceptives is
most widespread in developed countries.
Results of numerous studies (10 cohort and 60 case-control studies) have shown that the use
of oral hormonal combined contraceptives increases the risk of breast cancer.
6.6.1 Relative risks (RR) for malignancies due to the use of oral contraceptives
The value of relative risk for breast cancer related to the use of oral contraceptives has been
taken over from the study of the Collaborative Group on Hormonal Factors in Breast Cancer
(Oxford, UK, 1997). Based on the results of 54 epidemiological studies the Working Group has
found that the RR for breast cancer among women that regularly use oral contraception reaches
1.24.
6.6.2 Information used for exposure prevalence
The information on the prevalence of oral contraception use, i.e. combined hormonal
preparation of any generation, have been taken over from the Health Survey of the Serbian
population conducted in 2000. The prevalence of regular use of contraception among women aged
15 to 44 is presented in Table 23.
6.6.3 AF Calculations
Attributive fractions have been calculated according to the values of prevalence of use of
oral contraceptives and RR (1.24) for each of the age groups (Table 23). In 2005 the total of 3498
new cases of breast cancer and 1569 breast cancer deaths were recorded in Serbia, i.e. there were
393 new cases and 89 breast cancer deaths among women in the 15 to 45 yr age group. In this age
group, 6 new cases (1.5%) of breast cancer and one cancer death (1.1%) in 2005 could be attributed
to the use of oral contraception in Serbia. In the same year, and when all age groups were
combined, 0.2% of the new cases and 0.1% of breast cancer deaths could be attributed to the use of
oral contraceptives (Table 23).
46
Table 23. Prevalence of current OC use in women 15-45 years old in Serbia and attributable numbers of breast cancer cases and deaths, for the year 2005
Age % Current OC use AF* All breast
cancer cases
All breast cancer deaths
No. Breast cancer cases
attributable to OC use
No. Breast cancer death
attributable to OC use
15-19 5,0% 1.2% 0 0 0 0 20-24 4,2% 1.0% 1 1 0 0 25-29 5,6% 1.3% 16 4 0 0 30-34 7,7% 1.8% 37 9 1 0 35-39 7,0% 1.7% 107 16 2 0 40-44 5,3% 1.3% 232 59 3 1
Brest cancers 15-44 393 89 6 1 % of breast cancers 15-44 1.5% 1.1%
All breast cancers 3498 1569 % of all breast cancers 11.2% 5.7% 0.2% 0.1%
% of all cancers 24.5% 18.3% 0.04% 0.01% *Calculations taking an RR of 1.24
6.6.4 Discussion
According to results of numerous studies the use of oral contraception increases the risk of
breast cancer (Cogliano et al., 2005). The risk decreases over time, from the moment of
discontinuation of oral contraception onwards.
In addition to the stated risk, the use of OC among women is associated with numerous
beneficial effects: decreased risk of ovarian cancer and endometrial cancer, salpingitis, benign
diseases of the ovaries and breasts, extrauterine pregnancy and other health risks relating to
repetitive unwanted pregnancies. Also, the use of oral contraception increases the number of
contacts with health care services, which is beneficial for early detection of cervical cancer.
The prevalence of the use of oral contraception is several times lower in Serbia than in
developed European countries (UNFPA and WHO, 2000; UNFPA, 2003). The low prevalence of
the use of oral contraceptives in Serbia has resulted in a lower number of beast cancer cases and
deaths attributable to the use of OC.
On the other hand, it remains to answer whether the stated prevalence affects the positive
effect of OC use. It remains a fact that for quite a number of years women in Serbia visit their
gynecologists all too rarely, and the incidence and mortality rates of cancers of the cervix, ovaries
and endometrium are among the highest in Europe.
47
References
Cogliano V, Grosse Y, Baan R, et al for the WHO International Agency for Research on
Cancer. Carcinogenicity of combined oestrogen-progestagen contraceptives and menopausal
treatment. Lancet Oncology 2005;6:552–553.
http://monographs.iarc.fr/ENG/Meetings/91-contraceptives.pdf
IARC (1999) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol.
72, Hormonal Contraception and Post-Menopausal Hormonal Therapy, Lyon, IARC
Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal
contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and
100 239 women without breast cancer from 54 epidemiological studies. Collaborative Group on
Hormonal Factors in Breast Cancer. Lancet 1996;347:1713–1727.
Family Planning and Reproductive Health in Central and Eastern Europe and Newly
Independent States. UNFPA Division for Arab States and Europe and WHO Regional Office for
Europe Women’s and Reproductive Health Program, 2000
Contraceptive Prevalence in European Countries. Country Profiles for Population and
Reproductive Health: Policy Development and Indicators. CD from UNFPA, 2003
48
6.7 UV radiation
Exposure to solar and artificial UV radiation is the main environmental risk factor for the
occurrence of melanoma and other types of skin cancer. The most deleterious radiation is at
wavelengths between 290 to 320 nm (UVB), although there are indications that rays in the 320 to
400 nm range (UVA) may also be harmful. The melanoma pandemic recognized in recent decades
is attributed to the change of habits and increased exposure to UV rays, the fact that sunbathing has
been in, and increased amount of UV radiation that reaches the Earth’s surface because of damage
in the ozone layer.
Skin melanoma is not among the leading malignancies by the number of people affected.
Melanoma account for only 1-2% of all malignant tumors.
Due to relatively underestimated number of new cases of non-melanoma skin malignancies
in Serbia, this report does not include basocellular and planocellular skin cancers.
6.7.1 Relative risks (RR) for skin melanoma due to UV radiation RR for skin melanoma has not been calculated due to difficulties associated with
quantification of exposure to the sunlight.
6.7.2 Prevalence of exposure to UV rays Because of applied method of AF calculation, prevalence of exposure to UV radiation has
not been derived.
6.7.3 AF calculation
An alternative approach was used for the calculation of AF whereby proportion of skin
melanoma relating to exposure to UV radiation was estimated by comparison of the recorded
incidence of melanoma and melanoma incidence in absence of exposure to the Sun. The data of
Armstrong and Kricker (1993) were used, where the two of them investigated the difference
between the incidence of skin melanoma in native Australians and incidence of melanoma in
immigrants to Australia. They have estimated that 68% of skin melanoma may be attributed to
exposure to the natural UV radiation, irrespective of the time during life or type of sun exposure. In
our calculations, we used the specified AF value ( 68%) for both sexes.
In addition to AF values, Table 24 also illustrates the number of new cases and death cases
of skin melanoma in 2005 attributable to UV. In 2005, in Serbia , 160 new cases of melanoma in
men (0.99% of the total number of all new cancer cases) and 147 new cases of melanoma in women
49
(1.03% of the total number of all new cancer cases) could be attributed to UV radiation. UV
radiation is also attributable to 87 melanoma deaths in men (0.78% of all cancer deaths) and 65
cases of melanoma deaths in women (0.76% of all cancer deaths).
Table 24. Numbers of cancer cases and deaths attributable to UV light in Serbia, by sex, for the year 2005
Men Women Cancer AF θ Cases Deaths AF θ Cases Deaths
Melanoma 68.0% 160 87 68.0% 147 65 % all cancer - 0.99% 0.78% - 1.03% 0.76% θ Armstrong BK, Kricker A, 1993
6.7.4 Discussion
Based on the data from the Central Serbia Cancer Register in the period 1999 to 2005 the
average increase of the skin melanoma incidence has been noted in men and women (4.2% and
4.9%, respectively). In the same period, the average annual melanoma death rate rose by 1.2% in
men and 2.6% in women.
Worldwide, in the last four decades, the incidence of melanoma among Caucasians of both
sexes rose faster than any other malignancy, with the annual increase of 3-10%. In the USA, in the
mid nineties, melanoma was the leading malignancy of male Caucasians aged 35 to 44 years (Boyle
P. et al, 1995). Increasing melanoma incidence and death rates have been noted in all European
countries in the last decades (E. de Vries, J. Willem Coebergh, 2003). Stabilization of the melanoma
incidence and mortality rates in recent years has been noted in Scandinavian countries only.
Excessive exposure to UV radiation and absence of early detection programs for melanoma are still
present in the countries of the Southern and Eastern Europe.
Since there is no melanoma prevention program in Serbia, further increase of the melanoma
incidence and mortality rates may well be expected.
References International Agency for Research on Cancer. IARC. Monographs on the Evaluation of
Carcinogenic Risks to Humans, Vol. 24, Some Pharmaceutical Drugs, Lyon, IARC, 1980.
50
International Agency for Research on Cancer. IARC Monographs on the Evaluation of
Carcinogenic Risks to Humans, Vol. 40. Some Naturally Occurring and Synthetic Food
Components, Furocoumarins and Ultraviolet Radiation. Lyon, IARC, 1986.
International Agency for Research on Cancer. IARC Monographs on the Evaluation of
Carcinogenic Risks to Humans, Vol. 55. Solar and Ultraviolet Radiation. Lyon, IARC, 1992
International Agency for Research on Cancer. IARC Handbooks of Cancer Prevention,
Vol.5, Sunscreens. Lyon, IARC, 2001.
Armstrong BK, Kricker A. How much melanoma is caused by sun exposure? Melanoma
Res. 1993;3:395–401.
Boyle P., Vecehia C., Maisonneuve P., Zheng T., Maefarlane G. Cancer epidemiology an
prevention, in: Oxford Textbook of Oncology. Peckham M.; Pinedo B.; Veronesi U. (eds) Oxford
University Press, 1995.
E. de Vries, J. Willem Coebergh. Cutaneous malignant melanoma in Europe. European
Journal of Cancer , Volume 40 , Issue 16 , Pages 2355 - 2366, 2003.
51
7. Results
7.1 Pooled results
The number of cancer cases and cancer deaths attributable to individual risk factors are
presented in Tables 25 and 26. These tables illustrate proportions of cancer cases and cancer deaths
that are attributable to the selected risk factors.
Tobacco smoking, infectious agents and physical inactivity are risk factors that are
attributable to one in three malignancies in Serbia in 2005.
Tobacco smoking was attributable to 22.9% of new cancer cases in both sexes (32.6% in
men and 11.8% in women). Chronic infections are attributable to 6.0% of new cancer cases in both
sexes (2.3% in men and 10.2% in women), while physical inactivity was responsible for 4.0%
cancer cases in both sexes (1.6% in men and 6.6% in women). The share of other described
individual risk factors in cancers of any site ranged from 0.02% for oral contraceptives to 3.6% for
overweight and obesity (Table 25).
Table 25. Numbers of cancer cases and proportions attributable to various factors in Serbia, by sex, for the year 2005
Males Females Both sexes Risk factors Number % of all
cancers Number % of all
cancers Number % of all
cancers Tobacco 5277 32.55 1693 11.84 6970 22.85 Alcohol 719 4.44 236 1.65 955 3.13
Overweight and obesity 306 1.88 776 5.43 1082 3.55 Physical inactivity 264 1.63 940 6.58 1204 3.95 Infectious agents 379 2.34 1464 10.24 1843 6.04
Oral contraceptives - - 6 0.04 6 0.02 Ultraviolet light 160 0.99 147 1.03 307 1.01
In terms of mortality rates (Table 26), tobacco smoking was attributable to 28.3% cancer
deaths (39.1% in men and 14.3% in women), chronic infections were attributable to 4.5% cancer
deaths (1.9% in men and 7.9% in women), while physical inactivity was attributable to 3.5% cancer
deaths (1.6% in men and 5.9% in women).
52
Table 26. Numbers of cancer deaths and proportions attributable to various factors in Serbia, by sex, for the year 2005
Males Females Both sexes Risk factors Number % of all
cancers Number % of all
cancers Number % of all
cancers Tobacco 4365 39.08 1222 14.26 5587 28.30 Alcohol 503 4.50 120 1.40 623 3.16
Overweight and obesity 193 1.73 340 3.97 533 2.70 Physical inactivity 174 1.56 507 5.91 681 3.45 Infectious agents 214 1.92 680 7.93 894 4.53
Oral contraceptives - - 1 0.01 1 0.01 Ultraviolet light 87 0.78 65 0.76 152 0.77
7.2 Interactions among cancer risk factors
Prevalence of certain malignancies is frequently attributable to multiple risk factors. Studies
of interactions between two or among more risk factors enable more appropriate insight into their
joint impact on the occurrence of cancer.
Tables 27, 28 and 29 illustrate individual and total AF values in cases of cancer death that
may be attributed to risk factors investigated in 2005.
The following formula was used for the calculation of AF for the combined exposure to
factor 1 and factor 2 (combined AF):
AF = AF1 + AF2 – (AF1 * AF2),
The same formula was also used for the evaluation of combined AF in case of exposure to
multiple risks and for evaluation of fractions attributable to risk factors for all studied malignancies
in 2005.
According to the obtained results, out of the total number of cancer deaths in Serbia, 41.9%
(45.2% deceased men and 30.0% deceased women) may be attributed to joint effect of selected risk
factors in 2005.
53
Table 27. Summary of attributable fractions of cancer deaths (%) and estimate of the overall attributable fraction to an established risk factor by cancer site for men in Serbia in 2005
Risk factors Cancer site
Tobacco
Alcohol Overweight and obesity
Physical inactivity
Infectious agents
UV light
Total
Oral cavity and pharynx 70.9
46.8
-
-
6.7
-
83.1
Esophagus 51.1 33.8 36.5 - - - 73.1 Stomach 31.7 - - - 20.6 - 45.8 Liver 37.3 17.4 - - 28.4 - 72.0 Pancreas 26.3 - - - - - 26.3 Larynx 75.5 27.0 - - - - 82.1 Lung 83.8 - - - - - 83.8 Kidney 27.0 - 21.6 - - - 42.8 Urinary bladder 53.4
-
-
-
-
53.4
Colon-rectum - 7.5 10.1 12.3 - - 25.5 Hodgkin lymhoma - - - -
40.0
-
40.0
Non-Hodgkin lymhoma
-
-
-
-
8.0
-
8.0
Melanoma - - - - - 68.0 68.0
All cancers 39.1 4.5 1.7 1.6 1.9 0.8 45.2
Table 28. Summary of attributable fractions of cancer deaths (%) and estimate of the overall attributable fraction to an established risk factor by cancer site for women in Serbia in 2005
Risk factors Cancer site Tobacco Alcohol Overweight
and obesity Physical inactivity
Infectious agents
Oral contraceptives
UV light
Total
Oral cavity and pharynx 71.8
13.8
-
-
6.7
-
-
76.7
Esophagus 33.9 9.1 33.7 - - - - 35.3 Stomach 14.6 - - - 20.6 - - 32.2 Liver 16.7 3.8 - - 46.5 - - 56.9 Pancreas 18.1 - - - - - - 18.1 Larynx 63.8 9.9 - - - - - 67.4 Lung 70.3 - - - - - - 70.3 Kidney 11.7 - 21.8 - - - - 74.9 Urinary bladder 39.7
-
-
-
-
- - 39.7
Cervix uteri 23.5 - - 100.0 - - 100.0 Corpus uteri - 32.7 - - - - 32.7 Colon-rectum - 1.0 10.1 21.2 - - - 30.0 Breast - 4.8 9.4 17.7 - 0.1 - 27.6 Hodgkin lymhoma
-
-
-
-
40.0
-
-
40.0
Non-Hodgkin lymhoma
-
-
-
-
8.0
-
-
8.0
Melanoma - - - - - - 68.0 68.0
All cancers 14.3 1.4 4.0 5.9 7.9 0.01 0.8 30.0
54
Table 29. Summary of attributable fractions of cancer deaths (%) and estimate of the overall attributable fraction to an established risk factor by cancer site for both sex combined in Serbia in 2005
Risk factors Cancer site Tobacco Alcohol Overweight
and obesity Physical inactivity
Infectious agents
Oral contraceptives
UV light
Total
Oral cavity and pharynx 72.7
38.9
-
-
6.7
-
-
82.5
Esophagus 48.1 29.6 5.3 - - - - 41.7 Stomach 25.1 - - - 20.6 - - 40.5 Liver 28.8 11.7 - - 27.3 - - 53.4 Pancreas 22.4 - - - - - - 22.4 Larynx 39.1 13.3 - - - - - 86.3 Lung 80.8 - - - - - - 80.8 Kidney 20.9 - 21.5 - - - - 37.9 Urinary bladder 50.1
-
-
-
-
-
-
50.1
Cervix uteri 23.5 - - - 100.0 - - 100.0 Corpus uteri - - 32.7 - - - - 32.7 Colon-rectum - 4.7 10.1 22.1 - - - 33.9 Breast - 4.8 9.4 17.7 - 0.1 - 27.6 Hodgkin lymhoma
-
-
-
-
40.0
-
-
40.0
Non-Hodgkin lymhoma
-
-
-
-
8.0
-
-
8.0
Melanoma - - - - - - 68.0 68.0
All cancers 28.3 3.2 2.7 3.5 4.5 0.01 0.8 41.9
References
Doll R, Peto R. Epidemiology of cancer. In: Oxford Textbook of Medicine, 4th edition,
Oxford, Oxford University Press, 2005.
Roy P, Estève J. Using relative risk models for estimating synergy between two risk factors.
Stat Med 1998;17:1357–1373.
55
8. Discussion
This study estimated the number of new cancer cases and cancer deaths in 2005 attributable
to known risk factors.
This study analyzed the impact of agents in group 1 (tobacco smoking, alcohol drinking, use
of oral contraceptives, chronic infections and UV radiation) that, according to IARC, have causative
relation with cancer. Overweight and obesity have also been analyzed, as well as physical inactivity
since there is a sufficient body of evidence that absence of these factors has preventive effect to
some malignant tumors.
Epidemiological studies always question the accuracy of the data used for assessments.
Calculations of AF involve relative risks for the occurrence of malignancies due to exposure to
certain risk factors and prevalence of these risk factors in the studied populations.
Most of relative risks that we used were obtained from meta-analyses of various observational
epidemiological studies conducted in developed countries, while fewer were obtained from direct
estimates for the whole population, such as relative risks for malignancy due to exposure to EBV
and HPV infections and UV radiation. The use of meta-analyses for the relative risk assessment
reduces the impact of bias from individual studies, but it still remains a question how much these
relative risks, determined for the populations of developed countries, are representative for our
developing country.
The data on prevalence of the selected risk factors were usually derived from the Population
Health Survey in Serbia, conducted in 2000 and 2006. In addition to these sources of information on
the risk factor prevalence, other less reliable sources on exposure to risk factors were used, as well.
The smoking prevalence was obtained by interpolation of the data from the study conducted on a
population segment, and a survey conducted on the whole population. The data on the use of
alcoholic beverages obtained from the National Statistics Bureau were used for the assessment of
the prevalence of alcohol consumption. The data on the prevalence of chronic infections are based
on opinions of experts and reports on tested/examined persons in reference health institutions.
Prevalence studies have not been carried out for UV exposure. It is also questionable whether and
how much the exposure to some of the risk factors has changed.
In spite of all these problems we believe that , under the circumstances, we have conducted
the best possible assessment of proportions of cancer cases and cancer deaths that may be attributed
to certain risk factors in the population of Serbia in 2005.
56
To sum up, according to the results of our study, tobacco smoking, infectious agents and
physical inactivity are the most prominent factors attributable to the prevalence of cancer in Serbia
in 2005. Tobacco smoking is the main environmental avoidable cause of cancer in Serbia in both
men and women. After tobacco smoking, alcohol drinking is the second most common avoidable
cause of cancer of men in Serbia.
Prevalences of most of the studied risk factors reported in the population health surveys in
Serbia are high in comparison with other European countries, suggesting the need to promote
healthy life styles for prevention of certain malignancies and other chronic diseases.
References
Atanasković-Marković Z, Bjegović V, Janković S, Kocev N, Laaser U, Marinković J, et al.
The Burden of Disease and Injury in Serbia. Belgrade: Ministry of Health of the Republic of Serbia;
2003.
National Health Survey Serbia, 2000 – Institute of Public Health of Serbia; 2002
National Health Survey Serbia – Key finding. Belgrade: Ministry of Health, Republic of
Serbia; 2006
Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in
the United States today. J Natl Cancer Inst 1981;66:1191-1308.
Doll R, Peto R. Epidemiology of cancer. In: Oxford Textbook of Medicine, 4th edition.
Oxford, Oxford University Press, 2005.
Peto J. Cancer epidemiology in the last century and the next decade. Nature 2001;411:390-
395.
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