by Ting Wang, Yang Liu, Li Sima, Liang Shi, Zhaoming Wang, Chunhui Ni, Zhengdong Zhang, Meilin Wang
The -93G>A (rs1800734) polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC) risk. However, the results remain conflicting rather than conclusive. Objective
The aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC. Methods
To derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls) was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI) status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC. Results
The overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR?=?1.06, 95% CI?=?1.01–1.11; AA/AG versus GG: OR?=?1.06, 95% CI?=?1.01–1.11). This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR?=?2.52, 95% CI?=?1.94–3.28; AG versus GG: OR?=?1.29, 95% CI?=?1.10–1.52; AA/AG versus GG: OR?=?1.45, 95% CI?=?1.24–1.68; AA versus AG/GG: OR?=?2.29, 95% CI?=?1.78–2.96). Egger’s test did not show any evidence of publication bias. Conclusion
Our results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.