The hMLH1 -93G>A promoter polymorphism is associates with outcomes in oral squamous cell carcinoma patients

Ann Surg Oncol. 2014 Dec;21(13):4270-7. doi: 10.1245/s10434-014-3897-x. Epub 2014 Jul 22.

Abstract

Background: The aim of this study was to investigate the impact of hMLH1 polymorphisms on treatment outcomes in patients with oral squamous cell carcinoma (OSCC).

Methods: Genotypings were performed by direct DNA sequencing in peripheral blood leukocytes from 185 male OSCC patients. Patients received primary surgery with or without adjuvant radiotherapy. Two hMLH1 tag single nucleotide polymorphisms (SNPs)-rs1800734 (-93G>A in the promoter) and rs1540354 (in the third intron)-were chosen from the HapMap project. Overall survival (OS) and disease-free survival (DFS) were compared between different genotypes.

Results: The hMLH1 rs1800734 and rs1540354 polymorphisms were in weak linkage disequilibrium (r (2) = 0.456). OSCC patients with the rs1800734 AA genotype had a significantly poor prognosis in both OS and DFS. This SNP can also predict the outcomes of OSCC patients with postoperative adjuvant radiotherapy, especially in advanced stage; however, no significant differences in patient outcomes were found for the hMLH1 rs1540354 genotypes.

Conclusions: Our results demonstrate that the hMLH1 -93G>A SNP is found to be associated with patient outcomes in OSCC. This SNP can also predict their treatment outcome of radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / mortality
  • Mouth Neoplasms / pathology
  • MutL Protein Homolog 1
  • Neoplasm Grading
  • Neoplasm Staging
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Promoter Regions, Genetic / genetics*
  • Survival Rate

Substances

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