Genome-wide association study reveals novel genetic determinants of DNA repair capacity in lung cancer.

Published

Journal Article

Suboptimal cellular DNA repair capacity (DRC) has been shown to be associated with enhanced cancer risk, but genetic variants affecting the DRC phenotype have not been comprehensively investigated. In this study, with the available DRC phenotype data, we analyzed correlations between the DRC phenotype and genotypes detected by the Illumina 317K platform in 1,774 individuals of European ancestry from a Texas lung cancer genome-wide association study. The discovery phase was followed by a replication in an independent set of 1,374 cases and controls of European ancestry. We applied a generalized linear model with single nucleotide polymorphisms as predictors and DRC (a continuous variable) as the outcome. Covariates of age, sex, pack-years of smoking, DRC assay-related variables, and case-control status of the study participants were adjusted in the model. We validated that reduced DRC was associated with an increased risk of lung cancer in both independent datasets. Several suggestive loci that contributed to the DRC phenotype were defined in ERCC2/XPD, PHACTR2, and DUSP1. In summary, we determined that DRC is an independent risk factor for lung cancer, and we defined several genetic loci contributing to DRC phenotype.

Full Text

Duke Authors

Cited Authors

  • Wang, L-E; Gorlova, OY; Ying, J; Qiao, Y; Weng, S-F; Lee, AT; Gregersen, PK; Spitz, MR; Amos, CI; Wei, Q

Published Date

  • January 1, 2013

Published In

Volume / Issue

  • 73 / 1

Start / End Page

  • 256 - 264

PubMed ID

  • 23108145

Pubmed Central ID

  • 23108145

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-12-1915

Language

  • eng

Conference Location

  • United States