DNA mismatch repair gene polymorphisms affect survival in pancreatic cancer.

Published

Journal Article

PURPOSE: DNA mismatch repair (MMR) maintains genomic stability and mediates cellular response to DNA damage. We aim to demonstrate whether MMR genetic variants affect overall survival (OS) in pancreatic cancer. MATERIALS AND METHODS: Using the Sequenom method in genomic DNA, we retrospectively genotyped 102 single-nucleotide polymorphisms (SNPs) of 13 MMR genes from 706 patients with pancreatic adenocarcinoma seen at The University of Texas MD Anderson Cancer Center. Association between genotype and OS was evaluated using multivariable Cox proportional hazard regression models. RESULTS: At a false discovery rate of 1% (p ≤ .0015), 15 SNPs of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, TP73, and TREX1 in patients with localized disease (n = 333) and 6 SNPs of MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease (n = 373) were significantly associated with OS. In multivariable Cox proportional hazard regression models, SNPs of EXO1, MSH2, MSH3, PMS2L3, and TP73 in patients with localized disease, MSH2, MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease, and EXO1, MGMT, MSH2, MSH3, MSH6, PMS2L3, and TP73 in all patients remained significant predictors for OS (p ≤ .0015) after adjusting for all clinical predictors and all SNPs with p ≤ .0015 in single-locus analysis. Sixteen haplotypes of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, RECQL, TP73, and TREX1 significantly correlated with OS in all patients (p ≤ .001). CONCLUSION: MMR gene variants may have potential value as prognostic markers for OS in pancreatic cancer patients.

Full Text

Duke Authors

Cited Authors

  • Dong, X; Li, Y; Hess, KR; Abbruzzese, JL; Li, D

Published Date

  • 2011

Published In

Volume / Issue

  • 16 / 1

Start / End Page

  • 61 - 70

PubMed ID

  • 21212431

Pubmed Central ID

  • 21212431

Electronic International Standard Serial Number (EISSN)

  • 1549-490X

Digital Object Identifier (DOI)

  • 10.1634/theoncologist.2010-0127

Language

  • eng

Conference Location

  • United States