42
Sugar intake and Pancreatic Cancer University of Balamand Faculty of Health Sciences Research Methods FHSC288 Increased sugar intake and the risk of developing pancreatic cancer in Lebanese adults between the age of 50 and 80 years, a case-control study. El Jalbout Ralph Hamieh Cyma Massaad Nadine 1

FINAL Paper Research (2)

Embed Size (px)

Citation preview

Page 1: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

University of Balamand

Faculty of Health Sciences

Research Methods

FHSC288

Increased sugar intake and the risk of developing pancreatic cancer in Lebanese adults

between the age of 50 and 80 years, a case-control study.

El Jalbout Ralph

Hamieh Cyma

Massaad Nadine

May 2015

1

Page 2: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

Acknowledgment

We would like to thank our mentor Dr. Nivine Abbass for supporting and guiding

us during our research project. We also appreciate the explanations and advices provided

by our instructors Dr. Laurie Abi Habib and Miss Joumana Yeretzian which were very

beneficial. We are grateful to Miss Nadine Haddad for her help in the methods section

and developing the questionnaire. Finally, we would like to thank our University for the

open access to a rich database and to Miss Dolly Radi and Miss Sylvie Sleiman for the

help in obtaining articles from additional databases.

2

Page 3: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

Table of content

3

Page 4: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

I- Abstract

Ranked as the fourth leading cause of cancer-related deaths in the world, pancreatic

cancer is the causes of over 200 000 death yearly. In Lebanon as mentioned by the

Ministry of Public Health in 2005, 143 out of 7914 cancer patients reported having

pancreatic cancer, with comparable statistics in the years 2006, 2007 and 2008 for both

genders in equal proportions with a peek at the ages 62-63. Considering its low prognosis

and 5% survival rate after five years, preventing this disease is a necessity.

Hyperglycemia is one of the major underlying risk factors of pancreatic cancer

considering most of its patients are diagnosed with high glucose levels and diabetes.

Therefore, decreasing sugar consumption might help on decreasing the risk of developing

the disease and preventing its occurrence. In order to see the relation between sugar

intake and pancreatic cancer, a case-control study will be conducted for about five years.

A questionnaire and a food frequency checklist will be provided for the assessment of

pancreatic cancer patients in several hospitals in Lebanon. In parallel, four controls for

each case will be matched. Based on the results, we will try to deduce and find an

association between cancer patients’ diet and the disease.

Key words: Sugar Intake, Pancreatic Cancer, Cancer Prevention

4

Page 5: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

Table of contents

5

Page 6: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

Increased sugar intake and the risk of developing pancreatic cancer, in Lebanese adults

between the age of 50 and 80 years, a case-control study.

II- Introduction:

Globally, pancreatic cancer causes the death of over 200 000 people in the world

yearly (Michaud, 2004) and it is ranked as the fourth leading cause of cancer-related

deaths in the world (Hariharan et al, 2008). It is the fourth leading cause of death in the

United States out of all cancer types and the sixth in Europe. In 2014 in the USA,

Pancreatic cancer was diagnosed in 46,420 patients out of 1,665,540 (23,530 males and

22,890 females) and caused the death of 39,590 out of 585,720 (20,170 males and 19,420

females) (Siegel et al, 2014). This cancer is defined as the development and spread of

cancerous and malignant tumor cells in the pancreas affecting both the exocrine (which is

the most common function) and endocrine function of the organ (American Cancer

Society, 2015). The Exocrine function of the pancreas participates in the digestion

mechanism; the organ produces digestive enzymes used in the small intestine for

neutralization and breakdown. The Endocrine function is defined by the production of

hormones (glucagon and insulin mainly) for the regulation of glucose blood levels (Johns

Hopkins University, 2012).

Based on that, prevention is essential since it is considered as the most fatal

cancer providing a maximum of 5% survival chances for no more than five years of

duration (Nöthlings et al, 2007). Due to its high fatality rates, the incidence of pancreatic

cancer is directly associated with mortality; a lack in the screening tests for this disease

prevent the diagnosis until after its progression (Michaud, 2004). The incidence of this

6

Page 7: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

lethal disease is strongly associated with an increase with age especially between the ages

50 to 80 years; in the UK for example, 96% of pancreatic cancer patients were diagnosed

over the age of 50 years and 47% were diagnosed over the age of 75 between the years

2009 and 2011 (Office of National Statistics, 2011).

It has been evidenced that hyperglycemia is one of the underlying risk factors of

pancreatic cancer where “a large portion of pancreatic cancer patients suffer from either

hyperglycemia or diabetes, both of which are characterized by high blood glucose level.”

(Han et al, 2011). Moreover, there seems to be an association between increased sugar

consumption (including sweeteners, glucose, fructose, carbohydrate) and the increased

risk of becoming a pancreatic cancer patient as it has been demonstrated that

hyperglycemia aids in the proliferation and invasion capacity of pancreatic cells (Li et al,

2011). Sugar intake is basically the consumption of items containing any sort of glucose

or glucose derivatives such as sugar-sweetened foods or beverages, carbohydrates,

fructose (that is transformed on the body to glucose during digestion). In a multiple of

studies that considered the Arab world, the prevalence of pancreatic cancer is

significantly low but a little bit higher in Lebanon and Syria (Salim et al, 2009). Based on

the database of the Ministry of Public Health in Lebanon, in 2005, 143 of the total 7914

cancer patients reported had pancreatic cancer, in 2006 the values were 132 over 8491, in

2007 the values were 118 over 9552, and in 2008 the values were 137 over 9499. In the

National Cancer Registry (NCR) report “Cancer in Lebanon: 2005-2007” the cases of

pancreatic cancers are equal among genders but occur mainly in people older than 50

years with a mean of 62-63 years. “The age-specific incidence rates showed an increase

7

Page 8: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

starting the 50-55 age-group” according to the same report. In Lebanon, the

adenocarcinoma is the most recurrent type of pancreatic cancer notes the NCR.

Literature Review:

Based on that pancreatic cancer does not respond effectively to current cancer

treatment and has a low survival rate. Many studies worked on detecting risk factors in

order to prevent the tumor development. In their study, Nöthlings, Murphy, Wilkens,

Henderson, and Kolonel (2007) note that high glycemic load increased pancreatic cancer

onset. In their four years cohort study with 162,150 participants, 434 developed cancer.

The multiethnic study focused on African Americans, Japanese American, Latinos,

Native Hawaiians and whites (Nöthlings et al, 2007). Based on their follow up, dietary

assessment and results, Nöthlings et al (2007) pointed out that high sugar diet especially

fructose, put the individual at a higher risk of developing pancreatic cancer; foods like

fruits and juices are the key provider of fructose. Nöthlings et al (2007) mentioned that

long study periods are needed when working on pancreatic cancer because this

malignancy has a low occurrence rate. Overweight and obesity correlates with high sugar

and fructose intake and has to be taken into consideration.

In a prospective cohort study that has been done to investigate the relationship

between both dietary sugar and glycemic load and the risk for pancreatic cancer found

that any type of food that contribute to an increase in postprandial blood glucose levels

may have a great influence in a risk for pancreatic cancer (Michaud et al, 2002). In this

study, 121 700 women were followed up for 18 years with examination of their dietary

8

Page 9: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

intake. The results showed that high dietary sugar intakes along with a high glycemic

load and glycemic index were directly related to the increased risk of pancreatic cancer

for sedentary and overweight women. This a statistically significant increase in

pancreatic cancer risk by 86% for inactive women who consumed high fructose

compared to those who consumed a low fructose diet with a P-value of 0.02. However,

dietary intake did not reveal an association with the risk of pancreatic cancer for active

women (Michaud et al, 2002).

In another study done by Larsson, Bergkvist and Wolk (2006) diagnosed among

77 797 men and women between the ages 45 and 83 years adjusted for age, sex, smoking,

BMI, alcohol intake and energy 131 incident cases of pancreatic cancer, the participants

from Sweden were followed up from 1997 till June 2005 in a prospective study. Results

showed that a higher consumption of sugar-sweetened foods, soft drinks or sweetened

soups by participants, provided a greater risk of pancreatic cancer by 1.5 to 1.9 times than

in the group with the low consumption of these products (Larsson et al, 2006). However,

no association was found between the consumption of jam, marmalade or sweets and

pancreatic cancer considering that they contain a lot less sugar contents (30gr/serving)

than sweetened foods like soups (230gr/serving). Yet, it is important to note that the

participants handed a self-administered food frequency questionnaire, so

misclassification may have occurred between the sugar and the sweetened food

consumption. Moreover, this study correlates with another prospective cohort study done

on nurses and health professionals in the United States. It contributed to significant

results were women who consumed more than 3 sugar sweetened soft drinks per week

had a greater risk of 57% of pancreatic cancer than those who consumed less than 1 drink

9

Page 10: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

per week with a p-value of 0.05. On the other hand, no association between the

consumption of these items and pancreatic cancer was found among men (Schernhammer

et al, 2005). However, based on the work of Olson and Kurtz (2013), gender plays a role

and put men at a higher risk (13.5 for 100,000) of developing this type of cancer

compared to women (10.8 for 100,000). Thus, these studies are based on the fact that a

higher sugar intake causes elevated blood glucose levels which affect the activity of

pancreatic islet cells negatively causing glucose toxicity. Nevertheless, glucose toxicity

increases reactive oxygen that increases relatively the oxidative stress along with the

small presence of antioxidants in the islets cells, hence increasing the risk of P.C.

(Robertson,2004).

Further studies done by Ueno.Y, Makino.N, and Ito.M (2013) noted the

importance of early detection of pancreatic cancer to the scope of the treatment, they

found that risk factors can be associated with smoking, family history, age, sex, diabetes

mellitus, chronic pancreatitis, obesity and non-O blood group. In another study, done by

Permuth-Wey et al, results showed an increase in risk of pancreatic cancer if a relative

was diagnosed with the disease.

One major risk was obesity, according to a cohort study done in Japan by Lin.Y et

al, men and women with high BMI had risks 3.5 fold and 60% higher respectively, as

compared to those with normal BMI. Diabetes resulting from insufficient insulin

production by the pancreas, leading to high glucose levels in blood, has the highest

incidence among other diseases suspected to lead to pancreatic cancer, according to the

Committee for Pancreatic Cancer Registry in 2007.

10

Page 11: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

These studies suggest that there is an association between diabetes and the onset

of pancreatic cancer, from which it is understandable to further investigate the role of

glycemia.

Consistently, Gapstur, Gann, Lowe, Liu, Colangelo, and Dyer (2000) highlight the

necessity to prevent pancreatic cancer because of its extreme malignancy, metastasis and

late detection. In those conditions, they worked on the effect of “abnormal glucose

metabolism on pancreatic cancer” (Gapstur et al, 2000). They worked on employees from

the Chicago Heart Association Detection Project in Industry (CHA) cohort study and

measured their post-load Glucose level. Among the 35,658 participants, 96 men and 43

women died from pancreatic cancer. The post-load glucose level is the amount of glucose

in the blood one hour after the 50g challenge test, and in this study, 11.1mmol/L or

200g/dL was taken as cut off (Gapstur et al, 2000). The study concluded that participants

with initial post-load plasma glucose equal or higher than 11.1mmol/L are 2.2 times more

at risk of developing pancreatic cancer than participants with initial post-load plasma

glucose equal or lower than 6.6mmol/L (Gapstur et al, 2000). The abnormal glucose

metabolism associated with high insulin play a role in the development of pancreatic

cancer; insulin at high levels would act on promoting cellular growth especially

pancreatic cells reaching ultimately the cancer stage.

Hardey and Cowey concluded in a study on metabolic syndrome and its relation

to cancer, that hyperglycemia can directly damage the DNA of epithelium of pancreatic

duct via oxidative stress, hence leading to the onset of the cancer. Dominique.S,et al,

conducted a prospective study to find a relation between glycemic load and pancreatic

cancer, they controlled for several risk factors and observed a 53% increase in risk of P.C

11

Page 12: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

for women with high glycemic load intake as compared to those with low intake, similar

increase was observed when studying fructose level, 57%. In a different study done by

Suzuki et al, it was noted that fructose directly contributes to oxidative stress in growing

cells. On the other hand, a case-control study done by Lyon JL et al (1993), strong

association was found between pancreatic cancer and carbohydrate intake or added

sugars, but due to high mortality rate, the study design was prone to several bias and

errors.

In addition to many other studies that search for the presence of an association between

hyperglycemia and pancreatic cancer, Huxley et al (2005) saw in a meta-analysis of 36

studies on type II diabetes and pancreatic cancer, that there is an overestimate of the size

of the relationship between the two variables. This exaggeration also exists in other

studies due to bias, first since smaller studies reported the existence of the association and

second because the authors note the relationship obtained can be justified by the

existence of confounders such as smoking and obesity.

Rationale:

Based on the literature, pancreatic cancer is a rapidly fatal disease with a very low

survival rate (Michaud, 2004). Not to forget that this disease has a very poor prognosis

(Nöthlings et al, 2007). Moreover, the disease in its early stages, is asymptomatic and

silent; therefore, to decrease from its fatality rate it is critical to search for ways to

prevent its occurrence. Moving from this point, one of the most basic aspects eligible to

control in a healthy population is diet; that is why, looking at sugar intake and added

sweeteners in one’s diet, is beneficial to try and find an association. In addition, some

12

Page 13: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

studies suggested that an increase in glucose blood levels provoke an increase in insulin;

thus, insulin increase promotes the secretion of growth factors, which later on provoke

pancreatic cancer cell growth (Schneider et al, 2001). Zhou, Liotta, and Petricoin (2015)

noted in their work that the glycolitic activity of a tumor mass affects its diagnosis;

therefore, tumor with higher glycolitic activity and dependency on glucose have the

poorer prognosis. In the case of pancreatic cancer, they identified that those cells have

higher number of enzymes implicated in glucose metabolism and cellular respiration.

In addition to that, it is interesting to note that Lebanon is among the six world-leaders’

Arabic speaking countries for Diabetes type II (Badran, M & Laher.I. 2012), with

almost 53% of the Lebanese population living in Great Beirut diagnosed with Diabetes

(Jacob.S et al, 2005). In Lebanon, the Ministry of Public Health and the National Cancer

Registry defined that in the years 2005, 2006, 2007 and 2008, the occurrence of

pancreatic cancer was respectively 143 out of 7914 cancer patients, 132 out of 8491, 118

over 9552, and 137 over 9499. Unfortunately, the report lacked information concerning

effect of sugar on pancreatic cancer patients in Lebanon. This information is alarming

and highlights the importance of raising awareness among Lebanese population about the

dangerous consequences of uncontrolled sugar diet, one of which is pancreatic cancer.

Many underlying factors can increase the risk of pancreatic cancer (like: smoking, family

history, age, sex, diabetes mellitus, chronic pancreatitis, obesity and non-O blood group,

obesity, diabetes, etc…). We found that a focus on sugar intake would be more efficient

than any other risk factor bearing in mind that family history, age, sex, non-O blood

group factors cannot be controlled resulting from genetic predisposition. Diabetes

mellitus is directly related to sugar intake, not to forget that inappropriate sugar intake

13

Page 14: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

and dietary practices are the main causes for diabetes mellitus and pancreatic

dysfunction.

Therefore, our study will use a case-control study design where the exposure will be

sugar intake and the outcome will be pancreatic cancer. The sample will consist of

exposed and non-exposed cases and controls based on their sugar intake recall. This

might lead to the discovery of a positive link between sugar and pancreatic cancer.

Although most of the literature used a cohort study, taking into consideration the low

prevalence of pancreatic cancer, the limit in cost and time, we found that it is most

suitable to follow a case-control study design.

Consequently, in our case-control study, we are going to collect dietary information from

participants at a one point in time using a food frequency checklists that will helps us

determine the most frequent food items consumed during their past daily life routine.

Then, we want to check if any of the participants represent pancreatic cancer and relate it

to their dietary intake to study the relationship under investigation. By this design, we are

hoping to find the desired correlation between high sugar intake and risk for pancreatic

cancer.

Research Question:

Does sugar intake predispose Lebanese men and women between the age of 50 and 80

years living in Beirut to pancreatic cancer along five years of follow-up?  

Hypothesis:

The higher the sugar intake is, the higher is the risk of developing pancreatic cancer.

14

Page 15: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

Objectives:

The purpose of this study is to examine the effect of high sugar consumption on people

predisposing them to pancreatic cancer.

The objective is to find a true liaison between high sugar consumption and pancreatic

cancer. In order to do so, patients will be asked to recall their sugar intake in their diet

and associate it with their disease. The same will be done to the controls.

Methods:

The aim of our case control study design is to examine the Lebanese population

suffering from pancreatic cancer. Therefore we will be visiting several hospitals in

Lebanon to investigate the relationship between sugar intake(independent variable) and

risk of pancreatic cancer occurrence(dependent variable); such as Saint George Hospital

University Medical Center (SGHUMC), Hotel-Dieu de France, AUBMC, Rafic Hariri

Governmental Hospital in Beirut, Jabal Amel Hospital in Tyr, Nini Hospital and Al

Mounla Hospital in Tripoli, Khoury Hospital and Reyaa Hospital in the Bekaa, Sayidat

Al Ma’ounat in Byblos, Beshare Governmental Hospital in Bechare, Bhaniss Hospital in

Bhaniss in order to cover all regions. These hospitals were chosen based on their

geographical location, reputation and patients from different countries attend it and ask to

benefit from their services.

The attainable population will cover cases diagnosed with pancreatic cancer, in

the oncology department of hospitals. On the socio-demographical level, women and men

eligible for this study as cases will be those between 50 and 80 years of age. On the

clinical level, our cases are chosen based on their diagnosis with pancreatic cancer in the

15

Page 16: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

Lebanese Hospitals. We will try to get in touch with medical doctors and ask them to

collaborate with us in order to collect data related to patients diagnosed with pancreatic

cancer. An ethical letter will be sent to both the hospital and the oncologist explaining to

them our topic and its significance in addition to asking them for permission to work and

collaborate with them. The medical doctor will become part of the investigation, and all

he or she will do is report to us the incidence of a pancreatic cancer patient in the

oncology section.

The study will be based on the usage of questionnaires offering information about gender,

ager, weight in addition to occupation and habits such as smoking from which we will be

able to understand and collect information about dietary habits of our cases and controls.

Most importantly, a food frequency checklist will be given in order for the participants to

fill. This table provides us with food frequency intake and the amount of food eaten. All

the types of food sited contain molecules that the body will transform into glucose: such

as starch (in bread, pasta and rice), fructose (in fruits) and sucrose (in beverages and table

sugar). Each person will have two sheets with his ID, his/her answers will be reported

using the numbering underneath each category in a Likert Scale: going from “Never or

less than 1/month” (0) to “More than 5 a day” (7) and from “Very large amount/portion”

(4) to “Small amount/portion” (1) (Refer to Questionnaire sheet). The participant will

indicate the average food intake during the last 2 years, each year separately. Moreover,

the person will give an estimate of the quantity eaten. We found a similar case-control

study previously done which applied the same chronological demarche to assessing sugar

intake and pancreatic cancer.

16

Page 17: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

For each case, four controls will be chosen and matched in order to make our

control sample as representative as possible and minimize bias and chance considering

the high number of exclusion factors for both parties; we will be excluding the non-

Lebanese responders, those who do not belong to the age range or have family history of

pancreatic cancer disease or any kind of pancreatic disease (pancreatitis, insulinoma…) in

both controls and cases (Refer to Questionnaire sheet). These exclusions are used to try

and remove any sort of confounders. Matching will be based on their residence, age,

smoking habits and additional factors (diabetes) provided by the case (Refer to

Questionnaire sheet). More specifically, controls in the sample will be selected based on

random digit sampling method. The means that will be use would be the Lebanese white

pages book from which we will randomly select addresses belonging to the same area of

residency of the case or we will ask the municipality to provide us with the village or city

phone codes. The same question asked for the cases will be given to the controls during

the phone call. For both the cases and controls the purpose of the study will be explained

and information needed is going to be provided to check if they accept to cooperate. To

increase participation rate and minimize non response, we will be clearing up that we are

avoiding invasive and uncomfortable tests and simply ask for general information.

Moreover, we are going to control for smoking habits and diabetes by calculating the

odds ratio. We will hide from the participant the real purpose of assessing sugar and

pancreatic cancer not to trigger any recall bias in addition to an ethical issue (to be

discussed in the Ethics part).

To study the consistency and validity of the questionnaire, it will be first given to a

sample of volunteers not at all related to the study sample in order to test its questions.

17

Page 18: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

This sample of 10 to 20 people, contacting them via phone calls and explaining the aims

and objectives of the study, will provide us with feedback concerning the questions, time

needed to accomplish the task, difficulties and any comments concerning the questions.

Two weeks later, 5 people from this sample will be asked to fill the form again in order to

examine the consistency of the answers, whether the questions generate the same

responses or different ones. As a result, the questionnaire is finalized and used on the

study sample. Directly when a case is located, he or she will be given the questionnaire to

fill it in addition to an ID so that the privacy of the person would not be disturbed. After

collecting the cases information, the four controls will be matched based on the

requirements already mentioned. Each time a case is detected, the person will be given

the questionnaires and directly after that, the controls will be matched.

After a lap of time of two weeks, during which we would have entered the data and

wanted to revise them, the survey questions will be asked again to some randomly chosen

controls in order to test response accuracy. This will be done also to assess observer

reproducibility, compare the answers of the same person for consistency and control for

any recall bias.

The study will start on June 1st 2015 and will last five years till June 1st 2020 and this in

order to obtain a high number of pancreatic cancer cases considering the rareness of the

disease. All the cases reported during this period will be registered and questioned. This

is done in order to maximize our sample, making it larger so it will be more

representative and reduce sampling error. Based on that, there is no maximum sample

size.

18

Page 19: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

Following this, data analysis will start. The results will be compared to check

consistency. Then, data will be entered to Excel Software, and then check the entered

data to control and fix probable mistakes and errors in copying to ensure validity post-

data entry. After that, the data will be transferred to the SPSS Software for further

investigation in the biostatics and epidemiological field. Most importantly, the results

will help on assessing the sugar intake of this person. Each participant will obtain a score.

Based on the results of the control group, a cut off value will be deduced with a

score as an indicator for a low or high sugar intake by the cases. The relation between the

sugar diet and onset of pancreatic cancer will be established. The Odds ratio for all the

categories will be calculated in order to complete the investigation. To control for

diabetic patients and smokers, the Odds ratio will be calculated respectively and for non-

smokers or non-diabetics. According to our calculations, the role of smoking and diabetes

in developing pancreatic cancer will be deduced.

Limitations:

Sugar is not the only risk factor that has to be taken into consideration; other

elements can predispose a person to develop pancreatic cancer. Smoking is seen to

increase the risk by 75% (Olson & Kurtz, 2013). Obesity, diabetes, pancreatitis mainly, in

addition to alcohol and allergies are also predisposing agents. Most notably, family

history and genetic polymorphisms according to Olson and Kurtz (2013) increase the

chances of having many cases of cancer in the same family. Those mutations include

BRCA1, BRCA2, PALBA2 and many others. Therefore, as already mentioned, diabetes

and smoking will be controlled in addition of excluding other confounders.

19

Page 20: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

When it comes to the selection of cases and controls, difficulties will be faced. We will

need cooperation from the medical sector and the medical doctors to locate the cases,

considering that not all new cases will be reported. To be noted that cases can refuse

participating because of delicate matters and this is an important issue considering the

rareness the disease. Moreover, recall bias is important for both the cases and controls

especially if they have preconceived knowledge about pancreatic cancer; a person

diagnosed with pancreatic cancer would falsely associate the disease and a past

unexciting high sugar intake. Concerning the controls, that will be contacted by phone

calls; no accurate phone lists exist in Lebanon and not all houses have phones, disposing

us to selection bias. In addition, people can hang up, refuse to answer, or answer

inaccurately with bias.

Ethics

The ethical concern in this study is mainly the privacy of the participants and their

wellbeing.

First of all, the identity of a person will not be asked and the person will be given an ID

number once he or she enrolls in the study. We will then explain to the person the aim of

our study as detecting sugar in diet. The part about pancreatic cancer will be hidden in

order to avoid bias in recall, but most importantly to preserve the wellbeing of the

participants, especially the cases because not always they are informed with their disease.

If we reach a patient who does not know his clinical case and ask for his sugar intake

based on his disease, the psychological and emotional aspects of the person will be

disturbed. In this spirit, the P.C. will not be mentioned. The wellbeing of any of the

20

Page 21: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

participant should be the same after the survey as it was before it. The physician will

inform us about the case’s situation. An ethical letter will be sent to each health

establishment and oncologist in order to ask for permission and cooperation in localizing

and communicating with the case.

We will then explain to the participants that no follow up will be done and that all what is

asked is some basic information without any invasive intervention. No further

disturbance will be mad after. The participant will also know that we are students under

the cover of the UOB and SGHMC only, without further relation with the establishment.

We will explain the importance of diet and its assessment for one’s health and in

understanding it from a scientific point of view. Once all the explanation is completed

and the participant understood the situation, he or she will be asked to repeat what is

asked from them (what is the purpose, what will they do?). Following this, the case will

be asked for written consent on the questionnaire’s paper and the control will be asked by

phone for a verbal consent. No pressure of any kind will be applied on the participant, a

case who wishes not to enroll will reject the survey, and a control who wishes not answer

will hang up. A patient at the hospital may be seen as vulnerable because of his medical

condition, especially when faced to health workers. As mentioned, no pressure will be

exerted, and a person will freely decide what to do (this will be guaranteed by the consent

signed). Any of the participants can stop the survey when he or she decides to. All the

time a person needs to acknowledge the situation will be given, and all the time needed to

fill the survey will be provided, no one will be rushed.

Once a case in the hospital is declared, he or she will be added to the sample directly if he

or she accepts to participate. We will count on the reporter (medical doctors) to be fair in

21

Page 22: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

our selection. When it come to the controls, as said they will be chosen randomly base on

the phone area. In this study, very low are the physical, social, legal, economic or

psychological harms. Only those who wish to participate in the study will be asked

questions so no one’s time is lost. A mild psychological harm is avoided by not including

the P.C. assessment. The benefit to the participants will be moral as they help research

progress. Based on that, harms and benefit are balanced.

Moreover, our survey and questions will be tested by the university IRB to get feedback

and authorization to use it.

The data will be kept safe in a closed drawer, and only the three of us will have access to

it. At the end of the analysis, all the data will be burned and the results will be published.

Conclusion

Finally yet importantly, it is important to prevent P.C. because of its rapid onset, low

prognosis, and high mortality. Sugar was seen in the literature as being a predisposing

factor to develop P.C.. In this spirit, reducing sugar intake would help on reducing the

fact of developing P.C.. Our research will conduct a case-control study in order to assess

the relation between sugar intake and the development of P.C. in adults aged 50 to 80 in

all Lebanon. The study will be conducted using a survey and a sugar diet assessment grid.

This will allow us to effectively decide on the relation sugar and P.C. have in Lebanon. If

a positive association is found, future regulation of sugar diet should be done to all

persons with family history of P.C.. The aim of the study being to prevent P.C.,

awareness campaigns should be done to share with the society the results obtained.

22

Page 23: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

References

American Cancer Society (2015). Retrieved from:

http://www.cancer.org/cancer/pancreaticcancer/overviewguide/pancreatic-cancer-

overview-what-is-pancreatic-cancer

Dominique, M., Liu, S., Giovannucci, E., Willet, W., Graham, C., & Fuchs, C. (2002).

Dietary Sugar, Glycemic Load, and Pancreatic Cancer Risk in a Prospective

Study. Journal of the National Cancer Institute , 1293-1300.

Forsmark CE. Pancreatitis. In: Goldman L, Shafer AI, eds. Cecil Medicine. 24th ed.

Philadelphia, Pa: Saunders Elsevier; 2011:chap 46.

23

Page 24: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

Gapstur, S., Gann, P., Lowe, W., Liu, K., Colangelo, L., & Dyer, A., (2000). Abnormal

Glucose Metabolism and Pancreatic Cancer Mortality. Journal of American

Medical Association, 283 (19), 252-258

Han L, Ma Q, Li J, Liu H, Li W, Ma G, et al, (2011). High glucose promotes pancreatic

cancer cell proliferation via the induction of EGF expression and transactivation

of EGFR. PLoS One 2011;6:8.

Hariharan, D., Saied, A., & Kocher, H. (2008). Analysis of mortality rates for pancreatic

cancer across the world. HPB: The Official Journal of the International Hepato

Pancreato Biliary Association. 10(1), 58–62. doi: 10.1080/13651820701883148

Hirbli,K; Jambeine,M; Slim, Barakat,W; Habis,R; Francis,M., (2005). Prevalence of

Diabetes in Greater Beirut, Diabetes Care;1262-1262, DOI:

10.2337/diacare.28.5.1262

Huxley R, Ansary-Moghaddam A, Berrington de González A, et al. (2005). Type-II

diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer

92:2076-83

Ito, M., Naohiko, M., & Yoshiyuki, U. (2013). Glucose intolerance and the risk of

pancreatic cancer. Transl Gastrointest Cancer, 223-229.

Johns Hopkins University (2012). Retrieved from:

http://pathology.jhu.edu/pancreas/basicoverview3.php?area=ba

24

Page 25: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

Larsson S., Bergkvist L., Wolk A., (2006). Consumption of sugar and sugar-sweetened

foods and the risk of pancreatic cancer in a prospective study. The American

Journal of Clinical Nutrition 2006; 84, 1171-1176

Li J, Ma Q, Liu H, Guo K, Li F, Li W, et al, (2011). Relationship between neural

alteration and perineural invasion in pancreatic cancer patients with

hyperglycemia. PLoS One 2011;6:0017385

Lin Y, Kikuchi S, Tamakoshi A, Yagyu K, et al., (2007).Obesity, physical activity and

the risk of pancreatic cancer in a large Japanese cohort. Int J Cancer 120:2665-71.

Lyon JL, Slattery ML, Mahoney AW, Robison LM., (1993). Dietary intake as a risk

factor for cancer of the exocrine pancreas. Cancer Epidemiol Biomarkers

Prev;2:513–8

Michaud, DS. (2004, April). Epidemiology of pancreatic cancer. Retrieved from

http://www.ncbi.nlm.nih.gov/pubmed/15238885

Michaud DS. et al, (2011). Dietary sugar, glycemic load, and pancreatic cancer risk in a

prospective study. Journal of the National Cancer Institute 2002. 94(17). 1293-

1300

Office of National Statistics. Rterieved from:

http://www.ons.gov.uk/ons/rel/vsob1/cancer-statistics-registrations--england--

series-mb1-/index.html

25

Page 26: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

Badran, M. & Laher, I., (2006). Type II Diabetes Mellitus in Arabic-Speaking Countries.

International Journal of Endocrinology. doi:10.1155/2012/902873

Nöthlings, U., Murphy, S., Wilkens, L., Henderson, B., & Kolonel, L., (2007). Dietary

glycemic load, added sugars, and carbohydrates as risk factors for pancreatic

cancer: the Multiethnic Cohort Study1–4. American Journal of Clinical Nutrition,

86 , 1495–501

OLSON, S., & KURTZ, R.C., (2013). Epidemiology of Pancreatic Cancer and the Role

of Family History. Journal of Surgical Oncology, 107, 1–7

Permuth-Wey J, Egan KM., (2009). Family history is a significant risk factor for

pancreatic cancer: results from a systematic review and meta-analysis. Fam

Cancer;8:109-17

Robertson R.P., (2004). Chronic oxidative stress as a central mechanism for glucose

toxicity in pancreatic islet beta cells in diabetes. Journal of Biological Chemistry;

279:42351– 4.

Salim et al., (2009). Cancer epidemiology and control in the Arab world - past, present

and future. Asian Pacific Journal of Cancer Prevention; 10; 3-16

Schernhammer ES, Hu FB, Giovannucci E, et al., (2005). Sugar-sweetened soft drink

consumption and risk of pancreatic cancer in two prospective cohorts. Cancer

Epidemiology Biomarkers & Prevention;14:2098 –105.

26

Page 27: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

Siegel R, Ma J, Zou Z, & Jemal A., (2014). Cancer statistics, 2014. CA Cancer Journal

for Clinicians; 64:9-29

Suzuki K, Islam KN, Kaneto H, Ookawara T, Taniguchi N. (2000).The contribution of

fructose and nitric oxide to oxidative stress in hamster islet tumor (HIT) cells

through the inactivation of glutathione peroxidase. Electrophoresis;21:285–8

Zhou, W., Capello, M., Fredolini, C., Racanicchi L., Dugnani, E., Piemonti, L., Liotta,

L.A., Novelli, F., & Petricoin, E.F., (2013). Mass spectrometric analysis reveals

O-methylation of pyruvate kinase from pancreatic cancer cells. Anal Bioanal

Chem, 405, 4937–4943

Zhou, W., Liotta, L., & Petricoin, E., (2015). Cancer metabolism and mass spectrometry-

based proteomics. Cancer Letters, 356, 176–183

(2013). NCR 2008, Table B both gender: Frequency (nb) of incident cases by primary

site & age group. Lebanese Ministry of Public Health, National Cancer Registry.

Retrieved from

http://www.moph.gov.lb/Prevention/Surveillance/documents/BA2008.htm

(2013). NCR 2007, Table B both gender: Frequency (nb) of incident cases by primary

site & age group. Lebanese Ministry of Public Health, National Cancer Registry.

Retrieved from

http://www.moph.gov.lb/Prevention/Surveillance/documents/BA2007.htm

(2013). NCR 2006, Table B both gender: Frequency (nb) of incident cases by primary

site & age group. Lebanese Ministry of Public Health, National Cancer Registry.

27

Page 28: FINAL Paper Research (2)

Sugar intake and Pancreatic Cancer

Retrieved from

http://www.moph.gov.lb/Prevention/Surveillance/documents/BA2006.htm

(2013). NCR 2005, Table B both gender: Frequency (nb) of incident cases by primary

site & age group. Lebanese Ministry of Public Health, National Cancer Registry.

Retrieved from

http://www.moph.gov.lb/Prevention/Surveillance/documents/BA2005.htm

(2013). Cancer in Lebanon: 2005 – 2007. Lebanese Ministry of Public Health, National

Cancer Registry. Retrieved from

http://www.moph.gov.lb/Prevention/Surveillance/documents/leb_ncr_2005_7.pdf

28