title: Genetic variants of CYP2D6 gene and cancer risk: a HuGE systematic review and meta-analysis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Luan
authors.forename: Xi-Hua
authors.initials: XH
authors.lastname: Dong
authors.forename: Guo-Jiang
authors.initials: GJ
authors.lastname: Jin
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Man
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
chemical_list: D019389:Cytochrome P-450 CYP2D6