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Population-based study of the association of variants in mismatch repair genes with prostate cancer risk and outcomes.

Langeberg, Wendy J and Kwon, Erika M and Koopmeiners, Joseph S and Ostrander, Elaine A and Stanford, Janet L (2010) Population-based study of the association of variants in mismatch repair genes with prostate cancer risk and outcomes. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 19 (1). pp. 258-264. ISSN 1538-7755

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BACKGROUND: Mismatch repair (MMR) gene activity may be associated with prostate cancer risk and outcomes. This study evaluated whether single nucleotide polymorphisms (SNP) in key MMR genes are related to prostate cancer outcomes. METHODS: Data from two population-based case-control studies of prostate cancer among Caucasian and African-American men residing in King County, Washington were combined for this analysis. Cases (n = 1,458) were diagnosed with prostate cancer in 1993 to 1996 or 2002 to 2005 and were identified through the Seattle-Puget Sound Surveillance Epidemiology and End Results cancer registry. Controls (n = 1,351) were age-matched to cases and were identified through random digit dialing. Logistic regression was used to assess the relationship between haplotype-tagging SNPs and prostate cancer risk and disease aggressiveness. Cox proportional hazards regression was used to assess the relationship between SNPs and prostate cancer recurrence and prostate cancer-specific death. RESULTS: Nineteen SNPs were evaluated in the key MMR genes: five in MLH1, 10 in MSH2, and 4 in PMS2. Among Caucasian men, one SNP in MLH1 (rs9852810) was associated with overall prostate cancer risk [odds ratio, 1.21; 95% confidence interval (95% CI), 1.02, 1.44; P = 0.03], more aggressive prostate cancer (odds ratio, 1.49; 95% CI, 1.15, 1.91; P < 0.01), and prostate cancer recurrence (hazard ratio, 1.83; 95% CI, 1.18, 2.86; P < 0.01), but not prostate cancer-specific mortality. A nonsynonymous coding SNP in MLH1, rs1799977 (I219V), was also found to be associated with more aggressive disease. These results did not remain significant after adjusting for multiple comparisons. CONCLUSION: This population-based case-control study provides evidence for a possible association with a gene variant in MLH1 in relation to the risk of overall prostate cancer, more aggressive disease, and prostate cancer recurrence, which warrants replication.

Item Type: Article or Abstract
Additional Information: This article is available to subscribers only via the URL above for the first 12 months following publication.
DOI: 10.1158/1055-9965.EPI-09-0800
PubMed ID: 20056646
PMCID: PMC2825566
Grant Numbers: RO1 CA056678, RO1 CA082664, RO1 CA092579, P50 CA097186
Keywords or MeSH Headings: * Adaptor Proteins, Signal Transducing/genetics * Adenosine Triphosphatases/genetics * Adult * Aged * Case-Control Studies * DNA Mismatch Repair/genetics* * DNA Repair Enzymes/genetics * DNA-Binding Proteins/genetics * Genetic Predisposition to Disease* * Genotype * Humans * Male * Middle Aged * MutS Homolog 2 Protein/genetics * Neoplasm Recurrence, Local/genetics * Neoplasm Recurrence, Local/pathology * Nuclear Proteins/genetics * Polymorphism, Single Nucleotide * Prostatic Neoplasms/genetics* * Prostatic Neoplasms/pathology * Tumor Markers, Biological/genetics*
Subjects: Cellular and Organismal Processes > Genetic processes > Mutation
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: 03 Feb 2010 18:02
Last Modified: 14 Feb 2012 14:42

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