Association Of The AKR1C3 Polymorphism With Cancer Risk: A Meta-analysis

Background: Aldo-keto reductase(AKR) is a member of the oxidordeuctase superfamily. It contains approximately 190 members that fall into 16 families, and are found in all phyla. AKR1C3 is the family 1 member C3 of AKR superfamily. Human AKR1C3 gene encodes for NADPH-dependent oxidoreductases, and it can catalyze the conversion of aldehydes, ketones and some cancerogens to a series non-toxic or less toxic alcohols, which can keep cells out off damage. Human AKR1C3 gene is hightly polymorphic, it is mainly due to the presence of a plurality of single nucleotide polymorphisms( SNPs) of AKR1C3 gene. The mutations of single nucleotides in AKR1C3 gene lead to changes of the amino acid sequence in corresponding peptide chain, which may change the which may change the enzyme protein structure and activity, and then affect the cancer risk. Previous studies detected that AKR1C3 gene is involved in the occurrence and development of carcinoma. A number of studies investigating the association between AKR1C3 gene polymorphisms have been carried out, but the results of different studies are inconsistent. Therefore, we performed a meta-analysis to evaluate the effect of AKR1C3 gene single nucleotide polymorphisms on the risks of all cancer types.Methords: A literature search of PubMed, EMbase, OVID, CMB and Cochrane Library databases was conducted to collect all studies relevant to AKR1C3 gene single nucleotide polymorphisms on the risks of all cancer types. Excluding unqualified studies, then fixed or random effects model was selected based on heterogeneity test. Pooled Ors with 95% CIs were used to assess the correlation between AKR1C3 gene polymorphisms and cancer risks. Publication bias was examined with funnel plots. Sensitivity analysis was performed to evaluate the stability of results.Results: This meta-analysis included a total of 12 studies, there are 8 studies relevant to rs12529 polymorphism, 3 studies relevant to rs4881400 polymorphism, 4 studies relevant to rs2245191 polymorphism, 3 studies relevant to rs3763676 polymorphism, and 3 studies relevant to rs12387 polymorphisms. In the combined results, no significant association was observed between the AKR1C3 rs12529 polymorphism with the cancer risks. But the results of subgroup analysis of rs12529 polymorphism showed a significant association in Asians(Allele model G vs C, OR = 1.64, 95%CI 1.13–2.38, P = 0.009; Dominant gene model CG+GG vs CC, OR = 1.78, 95%CI 1.03–3.07, P = 0.04). In addition, this analysis also found carrying the rs3763676 locus GA or GG genotype have more cancer risk than AA genotype(Dominant gene model GA+GG vs AA,OR =1.20, 95%CI 1.03–1.40,P=0.02). In regard to other polymorphisms( rs4881400, rs2245191, rs12387), no significant association was observed between these polymorphism with the cancer risks.Conclusion: The results of this meta-analysis suggest that rs12529 polymorphism of AKR1C3 gene might be associated with increased risk of cancer in Asians,and carrying G allele may be a risk factor for cancer. In addition, this analysis also found carrying the AKR1C3 rs3763676 locus GA or GG genotype have more cancer risk than AA genotype. While rs4881400, rs2245191 and rs12387 polymorphisms of AKR1C3 gene were not associated with cancer risk. Further studies with larger sample sizes are needed to confirm these results.