Abstract for presentation at 11th International Congress of Human Genetics

GSTM1 and GSTT1 Polymorphisms modified associations between meat and heterocyclic amines intake and Risk of Colon Cancer: A Population-Based Case-Control Study in North Carolina

  • Dr Kui Huang, Department of Epidemiology, Pfizer, Inc, New York, United States
  • Dr Lesley Butler, Department of Public Health Sciences, University of California at Davis, California, United States
  • Dr Robert Sandler, Department of Epidemiology, University of North Carolina-Chapel Hill, North Carolina, United States
  • Dr Rashmi Sinha, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Maryland, United States
  • Dr Jennifer Hu, Department of Cancer Biology, Wake Forest University, North Carolina, United States
  • Dr Robert Millikan, Department of Epidemiology, University of North Carolina-Chapel Hill, North Carolina, United States

    • Heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) found in pan-fried, grilled, or barbecued well-done meat are known carcinogens and may increase risk of colon cancer. The metabolic enzymes, Glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) are involved in detoxification of HCAs and PAHs. In this study, we evaluated whether GSTM1 or GSTT1 polymorphisms modified associations among meat intake, exposure to HCAs and PAHs, and colon cancer in a population-based case-control study among African Americans and whites in North Carolina (554 cases and 874 controls). As part of a 150-item food frequency questionnaire, meat intake was assessed by cooking method and doneness and used to estimate individual HCA and PAH exposure. We found a small increased risk of colon cancer for individuals with GSTM1 null (Odds Ratio (OR)=1.27, 95 percent confidence interval (CI)=1.01-1.59) and a modest decreased risk for individuals with GSTT1 null (OR=0.67, 95%CI=0.52-0.86), compared to GSTM1 and GSTT1 present genotypes, respectively. For GSTM1 polymorphism, odds ratios for individual HCA exposure were statistically significantly increased among individuals with GSTM1 null genotype for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) (OR=1.39, 95%CI=0.66-2.92), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxa-line (DiMeIQx) (OR=2.39, 95%CI=1.19-4.79), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) (OR=1.07, 95%CI=0.59-1.91). Weak synergy was shown among these joint effects. With respect to GSTT1 polymorphism, there was evidence of joint effects between GSTT1 null genotype and red meat (OR=1.39, 95%CI=0.72-2.68) and PhIP intake (OR=0.51, 95%CI=0.27-0.99). Weak antagonism was shown among these joint effects. Individual and joint effects did not differ by race. These data suggest that GSTM1 and GSTT1 polymorphisms modify the associations among meat and HCA intake, in opposing directions, on the risk of colon cancer.

    Conference Organiser - ICMS Pty Ltd