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


CONCLUSIONS
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.
Agalliu
Ilir
I
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA. ilir.agalliu@einstein.yu.edu
Kwon
Erika M
EM
Salinas
Claudia A
CA
Koopmeiners
Joseph S
JS
Ostrander
Elaine A
EA
Stanford
Janet L
JL
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D024682:BRCA2 Protein / Q000235:genetics; D016009:Chi-Square Distribution; D004260:DNA Repair / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
D024682:BRCA2 Protein; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human