BACKGROUND: The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. METHODS: We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. RESULTS: Among the approximately 60,000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value = .004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value = .02). CONCLUSION: A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.
BACKGROUND: The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. METHODS: We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. RESULTS: Among the approximately 60,000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancerpatients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value = .004). The association was also statistically significant in an African American study population that included 210 prostate cancerpatients and 346 control subjects (one-sided P value = .02). CONCLUSION: A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.
Authors: Ethan M Lange; Jessica V Ribado; Kimberly A Zuhlke; Anna M Johnson; Gregory R Keele; Jin Li; Yunfei Wang; Qing Duan; Ge Li; Zhengrong Gao; Yun Li; Jianfeng Xu; S Lilly Zheng; Kathleen A Cooney Journal: Cancer Epidemiol Biomarkers Prev Date: 2015-12-15 Impact factor: 4.254
Authors: Franklin W Huang; Juan Miguel Mosquera; Andrea Garofalo; Coyin Oh; Maria Baco; Ali Amin-Mansour; Bokang Rabasha; Samira Bahl; Stephanie A Mullane; Brian D Robinson; Saud Aldubayan; Francesca Khani; Beerinder Karir; Eejung Kim; Jeremy Chimene-Weiss; Matan Hofree; Alessandro Romanel; Joseph R Osborne; Jong Wook Kim; Gissou Azabdaftari; Anna Woloszynska-Read; Karen Sfanos; Angelo M De Marzo; Francesca Demichelis; Stacey Gabriel; Eliezer M Van Allen; Jill Mesirov; Pablo Tamayo; Mark A Rubin; Isaac J Powell; Levi A Garraway Journal: Cancer Discov Date: 2017-05-17 Impact factor: 39.397
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Authors: Daxing Xie; Crystal Gore; Jun Liu; Rey-Chen Pong; Ralph Mason; Guiyang Hao; Michael Long; Wareef Kabbani; Luyang Yu; Haifeng Zhang; Hong Chen; Xiankai Sun; David A Boothman; Wang Min; Jer-Tsong Hsieh Journal: Proc Natl Acad Sci U S A Date: 2010-01-13 Impact factor: 11.205
Authors: Jianfeng Xu; Siqun Lilly Zheng; Sarah D Isaacs; Kathleen E Wiley; Fredrik Wiklund; Jielin Sun; A Karim Kader; Ge Li; Lina D Purcell; Seong-Tae Kim; Fang-Chi Hsu; Pär Stattin; Jonas Hugosson; Jan Adolfsson; Patrick C Walsh; Jeffrey M Trent; David Duggan; John Carpten; Henrik Grönberg; William B Isaacs Journal: Proc Natl Acad Sci U S A Date: 2010-01-11 Impact factor: 11.205