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MGMT Leu84Phe polymorphism contributes to cancer susceptibility: evidence from 44 case-control studies

Jun Liu1, Renxia Zhang, Fei Chen

  • 1Department of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Plos One
|October 3, 2013
PubMed
Abstract

Insights

The O(6)-methylguanine-DNA methyltransferase (MGMT) Leu84Phe polymorphism is linked to increased cancer risk, particularly lung cancer in Caucasians. This meta-analysis clarifies the association between this gene variant and cancer susceptibility.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • O(6)-methylguanine-DNA methyltransferase (MGMT) is crucial for DNA repair, directly reversing alkylating agent damage.
  • The MGMT Leu84Phe polymorphism has been investigated for its association with various cancer risks.
  • Previous studies yielded inconsistent results regarding the MGMT Leu84Phe polymorphism and cancer susceptibility.

Purpose of the Study:

  • To conduct a comprehensive meta-analysis of existing case-control studies.
  • To clarify the association between the MGMT Leu84Phe polymorphism and overall cancer risk.
  • To investigate potential ethnic and cancer-type specific associations.

Main Methods:

  • Meta-analysis of 44 independent case-control studies.
  • Statistical analysis of the MGMT Leu84Phe polymorphism (rs16906251) and cancer risk.
  • Subgroup analyses based on cancer type and ethnicity.

Main Results:

  • A significant association was found between the T allele (rs16906251) and increased cancer susceptibility under a recessive model (OR=1.30).
  • Increased lung cancer risk was observed, especially in Caucasians (TT vs CC, OR=1.67).
  • Colorectal cancer risk was significantly lower under a dominant model (OR=0.84), and no association was found in Asians.

Conclusions:

  • The MGMT Leu84Phe polymorphism is associated with susceptibility to certain cancers, notably lung cancer.
  • Ethnic differences in susceptibility exist, with a stronger association observed in Caucasian populations.
  • Further research is warranted to elucidate the precise role of MGMT genetic variations in cancer development.

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