Meat and Cancer: Assessment of Dietary Exposure to Heterocyclic Amines and Polycyclic Aromatic Hydrocarbons

Nicole Cardello Deziel, PhD, MHS

April 8, 2008

CLF Research Day

© 2006, Johns Hopkins University. All rights reserved.

© 2005, Johns Hopkins University. All rights reserved.

Introduction

• Meat intake associated with cancer (Norat and Riboli 2001; Norat et al. 2002)

• Biological mechanism not known

• Epidemiological studies of exposure to polycyclic aromatic hydrocarbons (PAH) and heterocyclic amines (HCA) and cancer suggestive but inconsistent

• Inconsistencies may be due to measurement error (Butler et al. 2003; Cantwell et al. 2004)

• Little known about how standard method compares to other methods, particularly biological monitoring (Sinha et al. 2001; Butler et al. 2003; Sinha et al. 2005; Gunter et al 2005; Cross et al. 2005, 2006; Li et al. 2007)

© 2006, Johns Hopkins University. All rights reserved.

© 2005, Johns Hopkins University. All rights reserved.

Objective

To evaluate dietary exposure to the HCA 2-amino-1-methyl-6-phenyl-imidazo-[4,5b]pyridine (PhIP) and the PAHs pyrene and benzo[a]pyrene (BaP) using three approaches:

(1) Meat-specific food frequency questionnaire (FFQ)combined with a food carcinogen database called CHARRED developed by the National Cancer Institute (NCI)

(2) NCI meat-specific diet diaries and CHARRED database

(3) Repeated biological monitoring of HCA and PAH urinary excretion products

© 2005, Johns Hopkins University. All rights reserved.

MethodsPopulation: 54 controls from a colorectal adenoma case-control study. Exclusion criteria: smoker or live with smoker, occupational exposure to PAH

FFQ Collection and Analysis: FFQ collected at 2 time points over an approximate 1-year period. Combined with NCI food carcinogen CHARRED database to estimate exposure to PhIP and BaP.

Diet Diary Collection and Analysis: Diet diaries collected at 3 time points over an approximate 1-year period. Combined with CHARRED database to estimate exposure to PhIP and BaP.

Urine Collection and Analysis: Overnight voids collected at 3 time points concurrent with diet diaries. Urine analyzed for PhIP and its conjugates and 1-hydroxypyrene-glucuronide (1-OHPG). Urinary cotinine assessed to confirm non-smoking status.

© 2005, Johns Hopkins University. All rights reserved.

NCI Meat-Specific FFQ

© 2005, Johns Hopkins University. All rights reserved.

Methods: FFQ Photographs

© 2005, Johns Hopkins University. All rights reserved.

01

02

03

04

0M

ean

Urin

ary

PhI

P (

pg/

ml)

0 200 400 600Mean PhIP Estimated from Diaries (ng/day)

Urinary PhIP vs. Diary-Based PhIP

Results: HCA

© 2005, Johns Hopkins University. All rights reserved.

05

10

15

Me

an U

rinar

y P

hIP

(p

g/m

l)

0 200 400 600Mean PhIP Estimated from Diaries (ng/day)

Urinary PhIP vs. Diary-Based PhIP, No Zeros

r=0.81 p<0.05

Results: HCA

© 2005, Johns Hopkins University. All rights reserved.

Results: PAH

Spearman correlations between urinary 1-OHPG (ng) and BaP intake (ng/day) estimated from diet diaries excluding participants with elevated urinary cotinine

Diet Diaries

Collect. 1

Diet Diaries

Collect. 2

Diet Diaries

Collect. 3 Mean of All

Diaries

1-OHPG Collect. 1 0.36* 0.35* 0.22

1-OHPG Collect. 2 0.13 0.21 0.19

1-OHPG Collect. 3 -0.06 0.32* 0.33*

Mean All Collect. 0.59**

*p<0.1 **p<0.05

© 2005, Johns Hopkins University. All rights reserved.

Spearman correlations between urinary 1-OHPG and BaP intake (ng/day) estimated from FFQs

 1-OHPG Collect. 1

1-OHPG Collect. 2

1-OHPG Collect. 3

Mean All Collect.

FFQ Baseline 0.42** -0.01 -0.04 0.39**

FFQ Follow-up 0.23 -0.23 0.02 0.12

Mean FFQ       0.28

**p<0.05

Results: PAH

© 2005, Johns Hopkins University. All rights reserved.

Conclusions• Among the three approaches for assessing dietary HCA exposure, a

correlation was only observed between the diary-database and urinary PhIP, when the analysis was restricted to values above zero or the detection limit (Spearman r=0.81, p<0.001).

• Lack of correlation may be due to small number of sampling days or short-comings of the FFQ and CHARRED database.

• For PAHs, the between-method correlation was strongest for BaP intake estimated from the diary-database and urinary 1-OHPG, after excluding participants with evidence of tobacco smoke exposure (elevated urinary cotinine) (Spearman r=0.59, p<0.05).

• Dietary BaP exposure estimated from the FFQ-database was also statistically significantly correlated with urinary 1-OHPG (Spearman r = 0.39, p<0.05).

• Further examination of discrepancies between the different methods may provide insight into ways to improve the dietary exposure assessment of PAH and HCA.

© 2006, Johns Hopkins University. All rights reserved.

© 2005, Johns Hopkins University. All rights reserved.

Significance for Public Health and Sustainability

• 35% of all cancer deaths in the U.S. are potentially avoidable through dietary changes (Doll and Peto 1981, Willett 1995)

• Improved exposure assessment methods could be applied in future epidemiological and risk studies to better understand the diet-disease link

• The growing awareness that a diet high in meat is deleterious to one’s health may be a powerful motivator for change, leading the way to decreased meat consumption

• Decreased consumption could lead to decreased production, guiding us toward a more livable future

© 2006, Johns Hopkins University. All rights reserved.

© 2005, Johns Hopkins University. All rights reserved.

Acknowledgements

Advisor: Dr. Paul Strickland

Co-Advisor: Dr. Tim Buckley

Colorectal Adenoma Study Team

Dr. Elizabeth Platz (Principal Investigator)

Kathy Schultz, RN

Julitta Brannock

Katie Sutcliffe

Dr. Strickland’s Lab

Salah Abubaker

National Cancer Institute

Dr. Rashmi Sinha

Johns Hopkins Center for a Livable Future

National Institute for Occupational Safety and Health

Maryland Cigarette Restitution Fund at Johns Hopkins