1. 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.

2. © 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.

3. © 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

4. © 2005, Johns Hopkins University. All rights reserved. Methods Population: 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.

5. © 2005, Johns Hopkins University. All rights reserved. NCI Meat-Specific FFQ

6. © 2005, Johns Hopkins University. All rights reserved. Methods: FFQ Photographs

7. © 2005, Johns Hopkins University. All rights reserved. Results: HCA

8. © 2005, Johns Hopkins University. All rights reserved. r=0.81 p<0.05 Results: HCA

9. © 2005, Johns Hopkins University. All rights reserved. Results: PAH

10. © 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 Baseline0.42**-0.01-0.040.39** FFQ Follow-up0.23-0.230.020.12 Mean FFQ 0.28 **p<0.05 Results: PAH

11. © 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.

12. © 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.

13. © 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