Methionine Synthase Reductase A66G Polymorphism is not Associated with Breast Cancer Susceptibility - a Meta-analysis

Shu Hu ,Shou-Ming Xi,Hong‐Chao Liu

doi:10.7314/apjcp.2014.15.7.3267

Abstract

Several studies have investigated the association between methionine synthase reductase (MTRR) A66G polymorphism and breast cancer risk, but controversial results were yielded. Therefore, we performed a meta-analysis to provide a more robust estimate of the effect of this polymorphism on susceptibility to breast cancer. Case-control studies investigating the relationship between MTRR A66G polymorphism and breast cancer risk were included by searching PubMed, EMBASE, China National Knowledge Infrastructure and Wanfang Database. Either fixed-effects or random-effects models were applied to calculate odds ratios(ORs) and 95% confidence intervals (CIs) by RevMan5.2 software. A total of 9 studies bearing 7,097 cases and 7,710 controls were included in the meta-analysis. The results were that the combined ORs and 95%CIs of MTRR 66AG, GG, (AG+GG) genotypes were 0.98(0.91-1.05), 1.06(0.97-1.16) and 1.02(0.94-1.10), respectively with p=0.52, 0.19 and 0.65. We also performed subgroup analysis by specific ethnicity. The results of the combined analysis of MTRR 66AG, GG, (AG+GG) genotypes and breast cancer in Asian descent were Z=0.50, 0.53 and 0.21, with p all>0.05; for breast cancer in Caucasian descent, the results were Z=1.14, 1.65 and 0.43, with p all>0.05. Our findings suggested that MTRR A66G polymorphism was not associated with breast cancer susceptibility.

Highlights

Breast cancer is the most common cancer among women around the world, with an estimated 232, 340 new cases in 2013 in the U.S alone, which represents close to 30% of all estimated new cancer cases in women (Siegel et al, 2013)
Study characteristics A total of 21 potentially relevant publications were identified based on the literature search criteria. 8 articles were unrelated and excluded firstly; during further screening, one study was excluded as case group were restricted to BRCA mutation carriers (Beetstra et al, 2008); The genotype frequencies of MTRR A66G polymorphism in cases and controls provided were not sufficient in three studies
9 case-control studies bearing 7097 cases and 7710 controls about the association between MTRR A66G polymorphism and breast cancer risk were included in this meta-analysis (Shrubsole et al, 2006; Xu et al, 2007; Lissowska et al, 2007; Kotsopoulos et al, 2008; Suzuki et al, 2008; Burcos et al, 2010; Sangrajrang et al, 2010; Lajin et al, 2012; Weiner et al, 2012)

Summary

Introduction

Breast cancer is the most common cancer among women around the world, with an estimated 232, 340 new cases in 2013 in the U.S alone, which represents close to 30% of all estimated new cancer cases in women (Siegel et al, 2013). It would be meaningful to identify biomarkers associated with the risk of breast cancer. Functional polymorphisms in genes encoding folatemetabolizing enzymes may have determined susceptibility to breast cancer. Several studies have investigated the association between methionine synthase reductase (MTRR) A66G polymorphism and breast cancer risk, but controversial results were yielded. We performed a meta-analysis to provide a more robust estimate of the effect of this polymorphism on susceptibility to breast cancer. Materials and Methods:Case-control studies investigating the relationship between MTRR A66G polymorphism and breast cancer risk were included by searching PubMed, EMBASE, China National Knowledge Infrastructure and Wanfang Database. The results were that the combined ORs and 95%CIs of MTRR 66AG, GG, (AG+GG) genotypes were 0.98(0.91-1.05), 1.06(0.97-1.16) and 1.02(0.94-1.10), respectively with p=0.52, 0.19 and 0.65. Conclusions: Our findings suggested that MTRR A66G polymorphism was not associated with breast cancer susceptibility

Methods

Results

Conclusion