Title: Carcinogen metabolism genes, red meat and poultry intake, and colorectal cancer risk.
Authors: Wang, Jun; Joshi, Amit D; Corral, Román; Siegmund, Kimberly D; Marchand, Loïc Le; Martinez, Maria Elena; Haile, Robert W; Ahnen, Dennis J; Sandler, Robert S; Lance, Peter; Stern, Mariana C
Published In Int J Cancer, (2012 Apr 15)
Abstract: Diets high in red meat are established risk factors for colorectal cancer (CRC). Carcinogenic compounds generated during meat cooking have been implicated as causal agents. We conducted a family-based case-control study to investigate the association between polymorphisms in carcinogen metabolism genes (CYP1A2 -154A>C, CYP1B1 Leu432Val, CYP2E1 -1054C>T, GSTP1 Ile105Val, PTGS2 5UTR -765, EPHX1 Tyr113His, NAT2 Ile114Thr, NAT2 Arg197Gln and NAT2 Gly286Glu) and CRC risk. We tested for gene-environment interactions using case-only analyses (N = 577) and compared statistically significant results to those obtained using case-unaffected sibling comparisons (N = 307 sibships). Our results suggested that CYP1A2 -154A>C might modify the association between intake of red meat cooked using high temperature methods and well done on the inside and CRC risk (case-only interaction OR = 1.53; 95% CI = 1.19-1.97; p = 0.0008) and the association between intake of red meat heavily browned on the outside and rectal cancer risk (case-only interaction OR = 0.65; 95% CI = 0.48-0.86; p = 0.003). We also found that GSTP1 Ile105Val might modify the association between intake of poultry cooked with high temperature methods and CRC risk (p = 0.0035), a finding that was stronger among rectal cancer cases. Our results support a role for heterocyclic amines that form in red meat as a potential explanation for the observed association between diets high in red meat and CRC. Our findings also suggest a possible role for diets high in poultry cooked at high temperatures in CRC risk.
PubMed ID: 21618522
MeSH Terms: Amines/metabolism; Animals; Aryl Hydrocarbon Hydroxylases/genetics; Arylamine N-Acetyltransferase/genetics; Carcinogens/metabolism*; Case-Control Studies; Colorectal Neoplasms/genetics*; Colorectal Neoplasms/metabolism*; Cooking/methods; Cyclooxygenase 2/genetics; Cytochrome P-450 CYP1A2/genetics; Cytochrome P-450 CYP1B1; Cytochrome P-450 CYP2E1/genetics; Diet; Epoxide Hydrolases/genetics; Female; Gene-Environment Interaction; Glutathione S-Transferase pi/genetics; Heterocyclic Compounds/metabolism; Humans; Male; Meat*; Middle Aged; Polymorphism, Single Nucleotide; Poultry; Risk Factors; Temperature