Faculty Collaboration Database

Significant effect of homologous recombination DNA repair gene polymorphisms on pancreatic cancer survival. Cancer Res 2006 Mar 15;66(6):3323-30

Date

03/17/2006

Pubmed ID

16540687

Pubmed Central ID

PMC1462866

DOI

10.1158/0008-5472.CAN-05-3032

Scopus ID

2-s2.0-33645514237 (requires institutional sign-in at Scopus site)   73 Citations

Abstract

Genetic variation in DNA repair may affect the clinical response to cytotoxic therapies. We investigated the effect of six single nucleotide polymorphisms of the RecQ1, RAD54L, XRCC2, and XRCC3 genes on overall survival of 378 patients with pancreatic adenocarcinoma who were treated at University of Texas M.D. Anderson Cancer Center during February 1999 to October 2004 and were followed up to October 2005. Genotypes were determined using the MassCode method. Survival was determined from pathologic diagnosis to death. Patients who were alive at the last follow-up evaluation were censored at that time. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare overall survival by genotypes. A significant effect on survival of all patients was observed for RecQ1 and RAD54L genes. The median survival time was 19.2, 14.7, and 13.2 months for the RecQ1 159 AA, AC, and CC genotypes, and 16.4, 13.3, and 10.3 months for RAD54L 157 CC, CT, and TT genotypes, respectively. A significantly reduced survival was associated with the variant alleles of XRCC2 R188H and XRCC3 A17893G in subgroup analysis. When the four genes were analyzed in combination, an increasing number of adverse alleles were associated with a significantly decreased survival. Subgroup analyses have shown that the genotype effect on survival was present among patients without metastatic disease or among patients who receive radiotherapy. These observations suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly affect the clinical outcome of patients with pancreatic cancer.

Author List

Li D, Liu H, Jiao L, Chang DZ, Beinart G, Wolff RA, Evans DB, Hassan MM, Abbruzzese JL

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphatases
Adult
Aged
Aged, 80 and over
Alleles
Carcinoma, Pancreatic Ductal
DNA Helicases
DNA Repair
DNA-Binding Proteins
Female
Humans
Male
Middle Aged
Neoplasm Staging
Nuclear Proteins
Pancreatic Neoplasms
Polymorphism, Single Nucleotide
Prognosis
RecQ Helicases
Recombination, Genetic
Survival Rate