Genetic Variants of CYP2D6 Gene and Cancer Risk: A HuGE Systematic Review and Meta-analysis

Objective: Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A largenumber of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate withcancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology(HuGE) review and meta-analysis was to summarize the evidence for associations.
Methods: Studies focusingon the relationship between CYP2D6 gene polymorphisms and susceptibility to cancer were selected from thePubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data wereextracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6and STATA Version 12.0 software. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated.
Results: According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646healthy controls, were included in the meta-analysis. The results showed that there was a positive associationbetween heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, wefound that homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58, 95%CI: 0.34-0.97,P=0.04). Similarly, the G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94,P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively).
Conclusion: This meta-analysis suggests that CYP2D6gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840in CYP2D6 gene might increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier (AG+ GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective factors.