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. 2010 Jan;19(1):258-64.
doi: 10.1158/1055-9965.EPI-09-0800.

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

Wendy J Langeberg  1 , Erika M Kwon, Joseph S Koopmeiners, Elaine A Ostrander, Janet L Stanford
Affiliations

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

Wendy J Langeberg et al. Cancer Epidemiol Biomarkers Prev. 2010 Jan.

Abstract

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.

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References

    1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71–96. - PubMed
    1. Salinas CA, Koopmeiners JS, Kwon EM, et al. Clinical utility of five genetic variants for predicting prostate cancer risk and mortality. Prostate. 2009 Mar 1;69(4):363–72. - PMC - PubMed
    1. Lynch HT, de la Chapelle A. Hereditary Colorectal Cancer. New England Journal of Medicine. 2003 Mar;348(10):919–32. - PubMed
    1. Colombo P, Patriarca C, Alfano RM, et al. Molecular disorders in transitional vs. peripheral zone prostate adenocarcinoma. Int J Cancer. 2001;94:383–389. - PubMed
    1. Dahiya R, Lee C, McCarville J, Hu W, Kaur G, Deng G. High frequency of genetic instability of microsatellites in human prostatic adenocarcinoma. Int J Cancer. 1997;72:762–767. - PubMed

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