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Genome-Wide Association Study Reveals Novel Genetic Determinants of DNA Repair Capacity in Lung Cancer
- Source :
- Cancer Research. 73:256-264
- Publication Year :
- 2013
- Publisher :
- American Association for Cancer Research (AACR), 2013.
-
Abstract
- 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. Cancer Res; 73(1); 256–64. ©2012 AACR.
- Subjects :
- Adult
Male
Cancer Research
Lung Neoplasms
DNA Repair
Genotype
Genome-wide association study
Single-nucleotide polymorphism
Biology
Polymorphism, Single Nucleotide
Article
Risk Factors
Polymorphism (computer science)
parasitic diseases
medicine
Humans
Genetic Predisposition to Disease
Risk factor
Lung cancer
Aged
Aged, 80 and over
Genetics
Middle Aged
medicine.disease
Phenotype
Oncology
ERCC2
Female
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 73
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....5cc7deec90327c467c0fb3d493527899