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Methionine synthase reductase A66G polymorphism contributes to tumor susceptibility: evidence from 35 case-control

Dong Han1, Chao Shen, Xiangning Meng

  • 1Laboratory of Medical Genetics, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, China.

Molecular Biology Reports
|May 7, 2011
PubMed

Insights

The Methionine synthase reductase (MTRR) A66G gene variant increases overall cancer risk, particularly in Asian populations. This MTRR A66G polymorphism may serve as a biomarker for identifying individuals at higher risk for certain cancers.

Area of Science:

  • Genetics and Molecular Biology
  • Cancer Research
  • Epidemiology

Background:

  • The Methionine synthase reductase (MTRR) gene plays a role in tumorigenesis by influencing DNA methylation via Methionine synthase (MTR) activation.
  • A common polymorphism in MTRR (A66G) results in an enzyme variant with reduced MTR affinity, and its association with cancer risk is debated.

Purpose of the Study:

  • To conduct a comprehensive meta-analysis to clarify the association between the MTRR A66G polymorphism and cancer risk.
  • To evaluate the impact of this polymorphism across different ethnic groups and cancer types.

Main Methods:

  • A meta-analysis was performed on data from 35 studies, including 18,661 cancer cases and 27,678 controls.
  • Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for various genetic models (homozygote, heterozygote, recessive, dominant).
  • Subgroup analyses by ethnicity and stratification by cancer type were conducted.

Main Results:

  • The MTRR G allele and GG genotype were significantly associated with increased overall cancer risk (G vs. A: OR=1.039; GG vs. AA: OR=1.094).
  • Significant increased risks were observed in Asian populations for the G allele and GG genotype across multiple genetic models.
  • Elevated cancer risk was found in 'other cancers' but not specifically in colorectal cancer, lymphoid leukemia, or breast cancer.

Conclusions:

  • The MTRR A66G polymorphism is associated with an increased risk of developing cancer.
  • This genetic variation, particularly in Asian populations, may serve as a valuable biomarker for cancer risk assessment.
  • Further research may elucidate the specific mechanisms linking MTRR A66G to tumorigenesis in different cancer types.

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