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

backgroundPolymorphisms 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.

methodsWe 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.

resultsSeventy 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; I(2) = 50.4%). When stratifying for tumour site, an OR of 0.84 (95% CI, 0.70-1.01; P for heterogeneity = 0.23, I(2) = 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, I(2) = 58.1%) was obtained for the bladder cancer from the hospital-based studies and on Caucasians.

conclusionsThis 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.