Carcinogen metabolism genes, meat intake, and colorectal cancer risk

We conducted a family based case-control study to investigate the association between xenobiotic 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 colorectal cancer (CRC) risk. We found GSTP1 Ile105Val is statistically significantly associated with colorectal cancer risk (OR=1.7, 95%CI=1.05-2.63, p=0.03). We tested the gene-meat interaction in proband-only sample (N=577) and then further examined in proband-sibling pairs (307 pairs). We only found CYP1B1 may modulate the effect of heavily browned poultry on the outside on CRC risk at border line significance (p=0.05). Our results also suggest that CYP1A2 may exert effects on risk of colon cancer and rectal cancer through different pathways when associated with cooked red meat intake or levels of doneness of red meat on the outside. In particular, when interacting with levels of doneness of red meat on the outside, individuals carrying AC or CC genotype had lower risk on colon cancer but much higher risk on rectal cancer (p for heterogeneity=0.05).