BACKGROUND: Because of the dramatically different clinical course of aggressive and indolent prostate carcinoma (PCa), markers that distinguish between these phenotypes are of critical importance. Apoptosis is an important protective mechanism for unrestrained cellular growth and metastasis. Therefore, dysfunction in this pathway is a key step in cancer progression. As such, genetic variants in apoptosis genes are potential markers of aggressive PCa. Recent work in breast carcinoma has implicated the histidine variant of CASP8 D302H (rs1045485) as a protective risk allele. METHODS: We tested the hypothesis that the H variant was protective for aggressive PCa in a pooled analysis of 796 aggressive cases and 2,060 controls. RESULTS: The H allele was associated with a reduced risk of aggressive PCa (OR(per allele) = 0.67, 95% CI: 0.54-0.83, P(trend) = 0.0003). The results were similar for European-Americans (OR(per allele) = 0.68; 95% CI: 0.54-0.86) and African-Americans (OR(per allele) = 0.61; 95% CI: 0.34-1.10). We further determined from the full series of 1,160 cases and 1,166 controls in the Prostate, Lung, Colorectal, Ovarian (PLCO) population that the protective effect of the H allele tended to be limited to high-grade and advanced PCa (all cases OR(per allele) = 0.94; 95% CI: 0.79-1.11; localized, low-grade disease OR(per allele) = 0.98; 95% CI: 0.79-1.23; and aggressive disease OR(per allele) = 0.73; 95% CI: 0.50-1.07). CONCLUSION: These results suggest that histidine variant of CASP8 D302H is a protective allele for aggressive PCa with potential utility for identification of patients at differential risk for this clinically significant phenotype.
BACKGROUND: Because of the dramatically different clinical course of aggressive and indolent prostate carcinoma (PCa), markers that distinguish between these phenotypes are of critical importance. Apoptosis is an important protective mechanism for unrestrained cellular growth and metastasis. Therefore, dysfunction in this pathway is a key step in cancer progression. As such, genetic variants in apoptosis genes are potential markers of aggressive PCa. Recent work in breast carcinoma has implicated the histidine variant of CASP8 D302H (rs1045485) as a protective risk allele. METHODS: We tested the hypothesis that the H variant was protective for aggressive PCa in a pooled analysis of 796 aggressive cases and 2,060 controls. RESULTS: The H allele was associated with a reduced risk of aggressive PCa (OR(per allele) = 0.67, 95% CI: 0.54-0.83, P(trend) = 0.0003). The results were similar for European-Americans (OR(per allele) = 0.68; 95% CI: 0.54-0.86) and African-Americans (OR(per allele) = 0.61; 95% CI: 0.34-1.10). We further determined from the full series of 1,160 cases and 1,166 controls in the Prostate, Lung, Colorectal, Ovarian (PLCO) population that the protective effect of the H allele tended to be limited to high-grade and advanced PCa (all cases OR(per allele) = 0.94; 95% CI: 0.79-1.11; localized, low-grade disease OR(per allele) = 0.98; 95% CI: 0.79-1.23; and aggressive disease OR(per allele) = 0.73; 95% CI: 0.50-1.07). CONCLUSION: These results suggest that histidine variant of CASP8 D302H is a protective allele for aggressive PCa with potential utility for identification of patients at differential risk for this clinically significant phenotype.
Authors: Laufey T Amundadottir; Patrick Sulem; Julius Gudmundsson; Agnar Helgason; Adam Baker; Bjarni A Agnarsson; Asgeir Sigurdsson; Kristrun R Benediktsdottir; Jean-Baptiste Cazier; Jesus Sainz; Margret Jakobsdottir; Jelena Kostic; Droplaug N Magnusdottir; Shyamali Ghosh; Kari Agnarsson; Birgitta Birgisdottir; Louise Le Roux; Adalheidur Olafsdottir; Thorarinn Blondal; Margret Andresdottir; Olafia Svandis Gretarsdottir; Jon T Bergthorsson; Daniel Gudbjartsson; Arnaldur Gylfason; Gudmar Thorleifsson; Andrei Manolescu; Kristleifur Kristjansson; Gudmundur Geirsson; Helgi Isaksson; Julie Douglas; Jan-Erik Johansson; Katarina Bälter; Fredrik Wiklund; James E Montie; Xiaoying Yu; Brian K Suarez; Carole Ober; Kathleen A Cooney; Henrik Gronberg; William J Catalona; Gudmundur V Einarsson; Rosa B Barkardottir; Jeffrey R Gulcher; Augustine Kong; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Genet Date: 2006-05-07 Impact factor: 38.330
Authors: Aruna V Sarma; Julie C McLaughlin; Lauren P Wallner; Rodney L Dunn; Kathleen A Cooney; David Schottenfeld; James E Montie; John T Wei Journal: J Urol Date: 2006-09 Impact factor: 7.450
Authors: Meredith Yeager; Nick Orr; Richard B Hayes; Kevin B Jacobs; Peter Kraft; Sholom Wacholder; Mark J Minichiello; Paul Fearnhead; Kai Yu; Nilanjan Chatterjee; Zhaoming Wang; Robert Welch; Brian J Staats; Eugenia E Calle; Heather Spencer Feigelson; Michael J Thun; Carmen Rodriguez; Demetrius Albanes; Jarmo Virtamo; Stephanie Weinstein; Fredrick R Schumacher; Edward Giovannucci; Walter C Willett; Geraldine Cancel-Tassin; Olivier Cussenot; Antoine Valeri; Gerald L Andriole; Edward P Gelmann; Margaret Tucker; Daniela S Gerhard; Joseph F Fraumeni; Robert Hoover; David J Hunter; Stephen J Chanock; Gilles Thomas Journal: Nat Genet Date: 2007-04-01 Impact factor: 38.330
Authors: Ruth Etzioni; David F Penson; Julie M Legler; Dante di Tommaso; Rob Boer; Peter H Gann; Eric J Feuer Journal: J Natl Cancer Inst Date: 2002-07-03 Impact factor: 13.506
Authors: Angela Cox; Alison M Dunning; Montserrat Garcia-Closas; Sabapathy Balasubramanian; Malcolm W R Reed; Karen A Pooley; Serena Scollen; Caroline Baynes; Bruce A J Ponder; Stephen Chanock; Jolanta Lissowska; Louise Brinton; Beata Peplonska; Melissa C Southey; John L Hopper; Margaret R E McCredie; Graham G Giles; Olivia Fletcher; Nichola Johnson; Isabel dos Santos Silva; Lorna Gibson; Stig E Bojesen; Børge G Nordestgaard; Christen K Axelsson; Diana Torres; Ute Hamann; Christina Justenhoven; Hiltrud Brauch; Jenny Chang-Claude; Silke Kropp; Angela Risch; Shan Wang-Gohrke; Peter Schürmann; Natalia Bogdanova; Thilo Dörk; Rainer Fagerholm; Kirsimari Aaltonen; Carl Blomqvist; Heli Nevanlinna; Sheila Seal; Anthony Renwick; Michael R Stratton; Nazneen Rahman; Suleeporn Sangrajrang; David Hughes; Fabrice Odefrey; Paul Brennan; Amanda B Spurdle; Georgia Chenevix-Trench; Jonathan Beesley; Arto Mannermaa; Jaana Hartikainen; Vesa Kataja; Veli-Matti Kosma; Fergus J Couch; Janet E Olson; Ellen L Goode; Annegien Broeks; Marjanka K Schmidt; Frans B L Hogervorst; Laura J Van't Veer; Daehee Kang; Keun-Young Yoo; Dong-Young Noh; Sei-Hyun Ahn; Sara Wedrén; Per Hall; Yen-Ling Low; Jianjun Liu; Roger L Milne; Gloria Ribas; Anna Gonzalez-Neira; Javier Benitez; Alice J Sigurdson; Denise L Stredrick; Bruce H Alexander; Jeffery P Struewing; Paul D P Pharoah; Douglas F Easton Journal: Nat Genet Date: 2007-02-11 Impact factor: 38.330
Authors: Gordon Fehringer; Peter Kraft; Paul D Pharoah; Rosalind A Eeles; Nilanjan Chatterjee; Fredrick R Schumacher; Joellen M Schildkraut; Sara Lindström; Paul Brennan; Heike Bickeböller; Richard S Houlston; Maria Teresa Landi; Neil Caporaso; Angela Risch; Ali Amin Al Olama; Sonja I Berndt; Edward L Giovannucci; Henrik Grönberg; Zsofia Kote-Jarai; Jing Ma; Kenneth Muir; Meir J Stampfer; Victoria L Stevens; Fredrik Wiklund; Walter C Willett; Ellen L Goode; Jennifer B Permuth; Harvey A Risch; Brett M Reid; Stephane Bezieau; Hermann Brenner; Andrew T Chan; Jenny Chang-Claude; Thomas J Hudson; Jonathan K Kocarnik; Polly A Newcomb; Robert E Schoen; Martha L Slattery; Emily White; Muriel A Adank; Habibul Ahsan; Kristiina Aittomäki; Laura Baglietto; Carl Blomquist; Federico Canzian; Kamila Czene; Isabel Dos-Santos-Silva; A Heather Eliassen; Jonine D Figueroa; Dieter Flesch-Janys; Olivia Fletcher; Montserrat Garcia-Closas; Mia M Gaudet; Nichola Johnson; Per Hall; Aditi Hazra; Rebecca Hein; Albert Hofman; John L Hopper; Astrid Irwanto; Mattias Johansson; Rudolf Kaaks; Muhammad G Kibriya; Peter Lichtner; Jianjun Liu; Eiliv Lund; Enes Makalic; Alfons Meindl; Bertram Müller-Myhsok; Taru A Muranen; Heli Nevanlinna; Petra H Peeters; Julian Peto; Ross L Prentice; Nazneen Rahman; Maria Jose Sanchez; Daniel F Schmidt; Rita K Schmutzler; Melissa C Southey; Rulla Tamimi; Ruth C Travis; Clare Turnbull; Andre G Uitterlinden; Zhaoming Wang; Alice S Whittemore; Xiaohong R Yang; Wei Zheng; Daniel D Buchanan; Graham Casey; David V Conti; Christopher K Edlund; Steven Gallinger; Robert W Haile; Mark Jenkins; Loïc Le Marchand; Li Li; Noralene M Lindor; Stephanie L Schmit; Stephen N Thibodeau; Michael O Woods; Thorunn Rafnar; Julius Gudmundsson; Simon N Stacey; Kari Stefansson; Patrick Sulem; Y Ann Chen; Jonathan P Tyrer; David C Christiani; Yongyue Wei; Hongbing Shen; Zhibin Hu; Xiao-Ou Shu; Kouya Shiraishi; Atsushi Takahashi; Yohan Bossé; Ma'en Obeidat; David Nickle; Wim Timens; Matthew L Freedman; Qiyuan Li; Daniela Seminara; Stephen J Chanock; Jian Gong; Ulrike Peters; Stephen B Gruber; Christopher I Amos; Thomas A Sellers; Douglas F Easton; David J Hunter; Christopher A Haiman; Brian E Henderson; Rayjean J Hung Journal: Cancer Res Date: 2016-04-20 Impact factor: 12.701