Current evidence on the relationship between three polymorphisms in the CYP1A2 gene and the risk of cancer

Abstract

CYP1A2 is an important cytochrome P450 enzyme that is involved in the metabolism of many clinical drugs and activation of some precarcinogens. Functional CYP1A2 polymorphisms are considered to exert significant effects on the risk of cancer, but the conclusions are inconsistent. Three commonly studied CYP1A2 polymorphisms, namely rs762551 (A>C), rs2069514 (G>A), and rs3569413 (T>delT), were selected to explore their association with the risk of development of cancer by meta-analysis of published case-control studies. Two investigators independently searched the PubMed, Embase, China National Knowledge Infrastructure, and the Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP1A2 polymorphisms and the risk of cancer were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. For rs762551, 37 studies were eligible (16 825 cases and 21 513 controls); for rs2069514, 15 studies were eligible (3677 cases and 5127 controls); and for rs3569413, eight studies were eligible (1607 cases and 2043 controls). The results showed that no significant associations with the risk of cancer were found in any model (allele contrast, codominant, dominant, or recessive model) in terms of rs2069514 and rs3569413 when all studies were pooled into a meta-analysis. However, when stratified by cancer type, a statistically significantly elevated risk of cancer was only found in lung cancer for rs3569413 (delT-allele vs. T-allele: OR=1.50, 95% CI=1.16-1.95). In the subgroup analysis by ethnicity, a significantly increased risk of cancer was found in the Caucasian population for rs3569413 (delT-allele vs. T-allele: OR=1.63, 95% CI=1.01-2.63). With respect to rs762551, we found that carriers of the C-allele showed an increased overall risk of developing cancer compared with A-allele carriers (C-allele vs. A-allele: OR=1.08, 95% CI=1.01-1.16). Further subgroup analyses showed that the rs762551 polymorphism was associated with an increased risk of cancer in the subgroup of Caucasians (C-allele vs. A-allele: OR=1.14, 95% CI=1.00-1.28; dominant model: OR=1.19, 95% CI=1.02-1.37). These results suggest that the rs3569413 polymorphism of the CYP1A2 gene is associated with an increased risk of lung cancer and the rs762551 polymorphism of the CYP1A2 gene might be a potential biomarker for the risk of cancer among Caucasians. Further large and well-designed studies are required to confirm this conclusion.