MLH1 polymorphisms and cancer risk: a meta-analysis based on 33 case-control studies

Asian Pac J Cancer Prev. 2012;13(3):901-7. doi: 10.7314/apjcp.2012.13.3.901.

Abstract

Objective: Cumulative evidence suggests that MLH1, the key component in the mismatch pathway, plays an important role in human cancers. Two potential functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in cancer risk. The aim of this meta-analysis was to summarize the evidence for associations.

Methods: Eligible studies were identified by searching the electronic literature PubMed, ScienceDirect and Embase databases for relevant reports and bibliographies. Studies were included if of case-control design investigating MLH1 polymorphisms (-93G>A and I219V) and cancer risk with sufficient raw data for analysis. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to evaluate the strength of associations.

Results: Our meta-analysis from 33 published case-control studies showed the variant A allele of -93G>A polymorphism to be associated with increased risk in all genetic models (AA vs. GG: OR = 1.22, 95% CI: 1.03-1.44), especially among non-Asians (AA vs. GG: OR = 1.28, 95% CI: 1.04-1.58). For the I219V polymorphism, however, there was no main effect associated with overall cancer risk in any genetic model.

Conclusions: The meta-analysis suggested that the MLH1 -93G>A polymorphism may be a biomarker of cancer susceptibility. Large sample association studies and assessment of gene-to-gene as well as gene-to-environment interactions are required to confirm these findings.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Case-Control Studies
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • MutL Protein Homolog 1
  • Neoplasms / genetics*
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Risk

Substances

  • Adaptor Proteins, Signal Transducing
  • MLH1 protein, human
  • Nuclear Proteins
  • MutL Protein Homolog 1