Lack of association between polymorphisms in the CYP1A2 gene and risk of cancer: Evidence from meta-analyses

Background: Polymorphisms in the CYP1A2 genes have the potential to affect the individual capacity to convert pre-carcinogens into carcinogens. With these comprehensive meta-analyses, we aimed to provide a quantitative assessment of the association between the published genetic association studies on CYP1A2 single nucleotide polymorphisms (SNPs) and the risk of cancer. Methods: We searched MEDLINE, ISI Web of Science and SCOPUS bibliographic online databases and databases of genome-wide association studies (GWAS). After data extraction, we calculated Odds Ratios (ORs) and 95 % confidence intervals (CIs) for the association between the retrieved CYP1A2 SNPs and cancer. Random effect model was used to calculate the pooled ORs. Begg and Egger tests, one-way sensitivity analysis were performed, when appropriate. We conducted stratified analyses by study design, sample size, ethnicity and tumour site. Results: Seventy case-control studies and one GWA study detailing on six different SNPs were included. Among the 71 included studies, 42 were population-based case-control studies, 28 hospital-based case-control studies and one genome-wide association study, including total of 47,413 cancer cases and 58,546 controls. The meta-analysis of 62 studies on rs762551, reported an OR of 1.03 (95 % CI, 0.96-1.12) for overall cancer (P for heterogeneity < 0.01; I2 = 50.4 %). When stratifying for tumour site, an OR of 0.84 (95 % CI, 0.70-1.01; P for heterogeneity = 0.23, I2 = 28.5 %) was reported for bladder cancer for those homozygous mutant of rs762551. An OR of 0.79 (95 % CI, 0.65-0.95; P for heterogeneity = 0.09, I2 = 58.1 %) was obtained for the bladder cancer from the hospital-based studies and on Caucasians. Conclusions: This large meta-analysis suggests no significant effect of the investigated CYP1A2 SNPs on cancer overall risk under various genetic models. However, when stratifying according to the tumour site, our results showed a borderline not significant OR of 0.84 (95 % CI, 0.70-1.01) for bladder cancer for those homozygous mutant of rs762551. Due to the limitations of our meta-analyses, the results should be interpreted with attention and need to be further confirmed by high-quality studies, for all the potential CYP1A2 SNPs.