Associations between CYP1A1 rs1048943 A > G and rs4646903 T > C genetic variations and colorectal cancer risk: Proof from 26 case-control studies

Abstract

Cytochrome P450 1A1 (CYP1A1) enzyme is one of the most important metabolizing enzymes responsible for the metabolism of numerous xenobiotics. Numerous individual case-control studies have investigated the associations between the CYP1A1 rs1048943 A > G and rs4646903 T > C genetic variations and colorectal cancer (CRC) risk, but the conclusions were controversial. To obtain a scientific conclusion, we performed a meta-analysis based on a total of 26 publications, including 20 studies with 8665 cases and 9953 controls on rs1048943 A > G and 19 studies with 6416 cases and 7551 controls on rs4646903 T > C, respectively. The pooled analysis indicated that rs1048943 A > G was associated with an increased risk of CRC (G vs. A: OR = 1.28, 95% CI = 1.08−1.52; GG vs. AA: OR = 1.54, 95% CI = 1.25−1.91; GA vs. AA: OR = 1.26, 95% CI = 1.00−1.60; GG/GA vs. AA: OR = 1.31, 95% CI = 1.05−1.64; GG vs. GA/AA: OR = 1.56, 95% CI = 1.26−1.91). Stratification analysis showed the association between rs1048943 A > G and CRC risk was more obvious in studies with the population-based (PB) design or high quality score. The association between rs4646903 T > C and CRC risk did not reach statistical significance in the pooled analysis as well as stratification analysis. This meta-analysis demonstrated CYP1A1 rs1048943 A > G may increase the susceptibility to CRC instead of rs4646903 T > C. This conclusion suggested CYP1A1 may contribute to the pathogenesis of CRC.