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.
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.
Authors: Y Chen; J Wang; M M Fraig; J Metcalf; W R Turner; N K Bissada; D K Watson; C W Schweinfest Journal: Cancer Res Date: 2001-05-15 Impact factor: 12.701
Authors: Yian Chen; Jiansong Wang; Mostafa M Fraig; Kelly Henderson; Nabil K Bissada; Dennis K Watson; Clifford W Schweinfest Journal: Int J Oncol Date: 2003-05 Impact factor: 5.650
Authors: P Colombo; C Patriarca; R M Alfano; B Cassani; G Ceva Grimaldi; M Roncalli; S Bosari; G Coggi; B Campo; V E Gould Journal: Int J Cancer Date: 2001-11-01 Impact factor: 7.396
Authors: Alfredo Velasco; Paul S Albert; Helmar Rosenberg; Carlos Martinez; Fredrick S Leach Journal: Cancer Biol Ther Date: 2002 Jul-Aug Impact factor: 4.742
Authors: Alfredo Velasco; Stephen M Hewitt; Paul S Albert; M Hossein; Helmar Rosenberg; Carlos Martinez; Arthur I Sagalowsky; John D McConnell; W Marston; Fredrick S Leach Journal: Cancer Date: 2002-02-01 Impact factor: 6.860
Authors: Liesel M Fitzgerald; Erika M Kwon; Joseph S Koopmeiners; Claudia A Salinas; Janet L Stanford; Elaine A Ostrander Journal: Clin Cancer Res Date: 2009-04-14 Impact factor: 12.531
Authors: Jiyoung Ahn; Adam S Kibel; Jong Y Park; Timothy R Rebbeck; Hanna Rennert; Janet L Stanford; Elaine A Ostrander; Stephen Chanock; Ming-Hsi Wang; Rama D Mittal; William B Isaacs; Elizabeth A Platz; Richard B Hayes Journal: Clin Cancer Res Date: 2011-02-22 Impact factor: 12.531
Authors: Jeannette T Bensen; Zongli Xu; Gary J Smith; James L Mohler; Elizabeth T H Fontham; Jack A Taylor Journal: Prostate Date: 2012-05-01 Impact factor: 4.104
Authors: Jong-Min Lee; Michael J Chao; Denise Harold; Kawther Abu Elneel; Tammy Gillis; Peter Holmans; Lesley Jones; Michael Orth; Richard H Myers; Seung Kwak; Vanessa C Wheeler; Marcy E MacDonald; James F Gusella Journal: Hum Mol Genet Date: 2017-10-01 Impact factor: 6.150