title: DNA mismatch repair gene polymorphisms affect survival in pancreatic cancer.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  MMR gene variants may have potential value as prognostic markers for OS in pancreatic cancer patients.
authors.affiliation: Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas MD Anderson Cancer Center, 1550 Holcombe Boulevard, Houston, Texas 77030-4009, USA.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Dong
authors.forename: Yanan
authors.initials: Y
authors.lastname: Li
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Donghui
authors.initials: D
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D053843:DNA Mismatch Repair / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D015996:Survival Rate