Genetic variation in DNA repair genes and prostate cancer risk: results from a population-based study.

Agalliu, Ilir and Kwon, Erika M and Salinas, Claudia A and Koopmeiners, Joseph S and Ostrander, Elaine A and Stanford, Janet L (2010) Genetic variation in DNA repair genes and prostate cancer risk: results from a population-based study. Cancer causes & control : CCC, 21 (2). pp. 289-300. ISSN 1573-7225

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Abstract

OBJECTIVE: DNA repair pathways are crucial to prevent accumulation of DNA damage and maintain genomic stability. Alterations of this pathway have been reported in many cancers. An increase in oxidative DNA damage or decrease in DNA repair capacity with aging or due to germline genetic variation may affect prostate cancer risk. METHODS: Pooled data from two population-based studies (1,457 cases and 1,351 controls) were analyzed to examine associations between 28 single-nucleotide polymorphisms (SNPs) in nine DNA repair genes (APEX1, BRCA2, ERCC2, ERCC4, MGMT, MUTYH, OGG1, XPC, and XRCC1) and prostate cancer risk. We also explored whether associations varied by smoking, by family history or clinical features of prostate cancer. RESULTS: There were no associations between these SNPs and overall risk of prostate cancer. Risks by genotype also did not vary by smoking or by family history of prostate cancer. Although two SNPs in BRCA2 (rs144848, rs1801406) and two SNPs in ERCC2 (rs1799793, rs13181) showed stronger associations with high Gleason score or advanced-stage tumors when comparing homozygous men carrying the minor versus major allele, results were not statistically significantly different between clinically aggressive and non-aggressive tumors. CONCLUSION: Overall, this study found no associations between prostate cancer and the SNPs in DNA repair genes. Given the complexity of this pathway and its crucial role in maintenance of genomic stability, a pathway-based analysis of all 150 genes in DNA repair pathways, as well as exploration of gene-environment interactions may be warranted.

Item Type:	Article or Abstract
Additional Information:	The original publication is available at springerlink.com.
DOI:	10.1007/s10552-009-9461-5
PubMed ID:	19902366
NIHMSID:	NIHMS165625
PMCID:	PMC2811225
Grant Numbers:	R01-CA56678, R01-CA092579 , N01-CN-05230
Keywords or MeSH Headings:	* Adult * African Americans/genetics * Aged * BRCA2 Protein/genetics * Chi-Square Distribution * DNA Repair/genetics* * European Continental Ancestry Group/genetics * Gene Frequency * Genetic Predisposition to Disease/genetics* * Genetic Variation * Genotype * Humans * Linkage Disequilibrium * Male * Middle Aged * Polymorphism, Single Nucleotide* * Population Surveillance * Prostatic Neoplasms/ethnology * Prostatic Neoplasms/genetics* * Risk Factors * Xeroderma Pigmentosum Group D Protein/genetics
Subjects:	Cellular and Organismal Processes > Genetic processes > DNA damage and repair Research Methodologies > Epidemiology > Risk assessment Diseases > Solid tumors > Prostate cancer
Depositing User:	Library Staff
Date Deposited:	17 Dec 2009 00:07
Last Modified:	14 Feb 2012 14:42
URI:	http://authors.fhcrc.org/id/eprint/350

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