BACKGROUND: Two prostate cancer genome-wide scans in populations of European ancestry identified several genetic variants that are strongly associated with prostate cancer risk. The effect of these risk variants and their cumulative effect in other populations are unknown. METHODS: We evaluated the association of 23 risk single-nucleotide polymorphisms (SNPs) with prostate cancer risk and clinical covariates (Gleason score, tumor aggressiveness, and age at diagnosis) in men of Japanese ancestry (311 case subjects and 1035 control subjects) using unconditional logistic regression. We also used logistic regression to test the association between increasing numbers of independently associated risk alleles and the risk of prostate cancer, prostate cancer aggressiveness, and age at diagnosis. All statistical tests were two-sided. RESULTS: Seven of the 23 SNPs (five independent loci) were associated with prostate cancer risk (P values ranged from .0084 to 2.3 x 10(-8) and effect sizes [estimated as odds ratios, ORs] ranged from 1.35 to 1.82). None of the seven SNPs was associated with Gleason score or aggressive disease. rs6983561 and rs4430796 were associated with age at diagnosis (Ps = .0188 and .0339, respectively). Men with six or more risk alleles (27% of case patients and 11% of control subjects) had a higher risk of prostate cancer than men with two or fewer risk alleles (7% of case patients and 20% of control subjects) (OR = 6.22, P = 1.5 x 10(-12)). CONCLUSIONS: These results highlight the critical importance of considering ancestry in understanding how risk alleles influence disease and suggest that risk estimates and variants differ across populations. It is important to perform studies in multiple ancestral populations so that the composite genetic architecture of prostate cancer can be rigorously addressed.
BACKGROUND: Two prostate cancer genome-wide scans in populations of European ancestry identified several genetic variants that are strongly associated with prostate cancer risk. The effect of these risk variants and their cumulative effect in other populations are unknown. METHODS: We evaluated the association of 23 risk single-nucleotide polymorphisms (SNPs) with prostate cancer risk and clinical covariates (Gleason score, tumor aggressiveness, and age at diagnosis) in men of Japanese ancestry (311 case subjects and 1035 control subjects) using unconditional logistic regression. We also used logistic regression to test the association between increasing numbers of independently associated risk alleles and the risk of prostate cancer, prostate cancer aggressiveness, and age at diagnosis. All statistical tests were two-sided. RESULTS: Seven of the 23 SNPs (five independent loci) were associated with prostate cancer risk (P values ranged from .0084 to 2.3 x 10(-8) and effect sizes [estimated as odds ratios, ORs] ranged from 1.35 to 1.82). None of the seven SNPs was associated with Gleason score or aggressive disease. rs6983561 and rs4430796 were associated with age at diagnosis (Ps = .0188 and .0339, respectively). Men with six or more risk alleles (27% of case patients and 11% of control subjects) had a higher risk of prostate cancer than men with two or fewer risk alleles (7% of case patients and 20% of control subjects) (OR = 6.22, P = 1.5 x 10(-12)). CONCLUSIONS: These results highlight the critical importance of considering ancestry in understanding how risk alleles influence disease and suggest that risk estimates and variants differ across populations. It is important to perform studies in multiple ancestral populations so that the composite genetic architecture of prostate cancer can be rigorously addressed.
Authors: Sarah M Troutman; Tristan M Sissung; Cheryl D Cropp; David J Venzon; Shawn D Spencer; Bamidele A Adesunloye; Xuan Huang; Fatima H Karzai; Douglas K Price; William D Figg Journal: Oncologist Date: 2012-03-01
Authors: Chiara Grisanzio; Lillian Werner; David Takeda; Bisola C Awoyemi; Mark M Pomerantz; Hiroki Yamada; Prasanna Sooriakumaran; Brian D Robinson; Robert Leung; Anna C Schinzel; Ian Mills; Helen Ross-Adams; David E Neal; Masahito Kido; Toshihiro Yamamoto; Gillian Petrozziello; Edward C Stack; Rosina Lis; Philip W Kantoff; Massimo Loda; Oliver Sartor; Shin Egawa; Ashutosh K Tewari; William C Hahn; Matthew L Freedman Journal: Proc Natl Acad Sci U S A Date: 2012-06-22 Impact factor: 11.205
Authors: Marian Beekman; Christa Nederstigt; H Eka D Suchiman; Dennis Kremer; Ruud van der Breggen; Nico Lakenberg; Wendimagegn Ghidey Alemayehu; Anton J M de Craen; Rudi G J Westendorp; Dorret I Boomsma; Eco J C de Geus; Jeanine J Houwing-Duistermaat; Bastiaan T Heijmans; P Eline Slagboom Journal: Proc Natl Acad Sci U S A Date: 2010-10-04 Impact factor: 11.205
Authors: Yizhen Lu; Jielin Sun; Andrew K Kader; Seong-Tae Kim; Jin-Woo Kim; Wennuan Liu; Jishan Sun; Daru Lu; Junjie Feng; Yi Zhu; Tao Jin; Zheng Zhang; Latchezar Dimitrov; James Lowey; Kevin Campbell; Edward Suh; David Duggan; John Carpten; Jeffrey M Trent; Henrik Gronberg; S Lilly Zheng; William B Isaacs; Jianfeng Xu Journal: Prostate Date: 2011-06-10 Impact factor: 4.104
Authors: Katherine S Elliott; Eleftheria Zeggini; Mark I McCarthy; Julius Gudmundsson; Patrick Sulem; Simon N Stacey; Steinunn Thorlacius; Laufey Amundadottir; Henrik Grönberg; Jianfeng Xu; Valerie Gaborieau; Rosalind A Eeles; David E Neal; Jenny L Donovan; Freddie C Hamdy; Kenneth Muir; Shih-Jen Hwang; Margaret R Spitz; Brent Zanke; Luis Carvajal-Carmona; Kevin M Brown; Nicholas K Hayward; Stuart Macgregor; Ian P M Tomlinson; Mathieu Lemire; Christopher I Amos; Joanne M Murabito; William B Isaacs; Douglas F Easton; Paul Brennan; Rosa B Barkardottir; Daniel F Gudbjartsson; Thorunn Rafnar; David J Hunter; Stephen J Chanock; Kari Stefansson; John P A Ioannidis Journal: PLoS One Date: 2010-05-28 Impact factor: 3.240