Genetic polymorphisms of phase I metabolizing enzyme genes, their interaction with lifetime grilled and smoked meat intake, and breast cancer incidence

Abstract

Purpose To examine associations between 22 CYP single nucleotide polymorphisms (SNPs) and breast cancer incidence and their interactions with grilled–smoked meat intake, a source of polycyclic aromatic hydrocarbons. Methods White women with first primary in situ or invasive breast cancer (n = 988) and frequency-matched controls (n = 1021) from a population-based study were interviewed to assess lifetime grilled–smoked meat intake. SNPs with minor allele frequencies of greater than 0.05 were selected because of their links to carcinogenesis. We used multivariable unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Breast cancer was inversely associated with CYP1A1 rs104C8943 AG + GG genotype (OR = 0.71, 95% CI = 0.50–0.99; vs. AA genotype) and positively associated with CYP1B1 rs10175338 TT genotype (OR = 1.59, 95% CI = 1.12–2.26; vs. GG genotype) and the CYP3A4 rs2242480 CT + TT genotype (OR = 1.25, 95% CI = 1.00–1.56; vs. CC genotype). The sum of the number of “at-risk” alleles for the CYP SNPs was positively associated with breast cancer incidence (4–6 “at-risk” alleles OR = 2.33, 95% CI = 1.37–3.99 vs. 0-1 alleles; PTrend < .01). We observed multiplicative and additive interactions (P < .05) between grilled–smoked meat intake (low vs. high) with CYP1A1 rs1048943 and CYP1B1 rs10175338 SNPs. Conclusions Phase I metabolizing enzyme gene SNPs may play a role in breast cancer development and may modify the grilled–smoked meat intake–breast cancer association.