Abstract
Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate with cancer 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. Studies focusing on the relationship between CYP2D6 gene polymorphisms and susceptibility to cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646 healthy controls, were included in the meta-analysis. The results showed that there was a positive association between heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, we found 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 rs35742686 had 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). This meta-analysis suggests that CYP2D6 gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840 in 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.
Highlights
Cytochrome P450 (CYP450) is a large and diverse group of metabolic enzymes containing heme, consisted by many isozyme, known as P450 gene superfamily (Wexler et al, 2004)
The results showed that there was a positive association between heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95% confidence intervals (95%CIs): 1.14-3.21, P=0.01)
The G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; Odds ratios (ORs)=0.60, 95%CI: 0.38-0.94, P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively). This meta-analysis suggests that Cytochrome P450 2D6 (CYP2D6) gene polymorphisms are involved in the pathogenesis of various cancers
Summary
Cytochrome P450 (CYP450) is a large and diverse group of metabolic enzymes containing heme, consisted by many isozyme, known as P450 gene superfamily (Wexler et al, 2004). CYP450 is mainly in the endoplasmic reticulum of liver, involved in the endogenous and exogenous substances with biological transformation (Lewis et al, 2004). CYP450 gene families, 36 gene subgroups in mammals. The research work mainly focus on CYP1A, CYP2A6. CYP2D6, CYP2C9, CYP2C19 and CYP3A (Foster et al, 2003; Agundez et al, 2004).
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