BACKGROUND: Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder. METHODS: To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphisms (SNPs) in the 8q24 risk regions spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, 3alphadiol G, and bioavailable testosterone), and sex hormone-binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Age-adjusted linear regression models were used to determine the association between the SNPs in an additive genetic model and log-transformed biomarker levels. RESULTS: Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P < 1.1 x 10(-3)) and bioavailable testosterone (P < 6.3 x 10(-4)). Suggestive associations were seen for a cluster of nine SNPs in prostate cancer risk region 1 and androstenedione (P < 0.05). CONCLUSIONS: These preliminary findings require confirmation in larger studies but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions might correlate with androgen levels. IMPACT: These results might provide some clues for the strong link between 8q24 and prostate cancer risk.
RCT Entities:
BACKGROUND: Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder. METHODS: To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphisms (SNPs) in the 8q24 risk regions spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, 3alphadiol G, and bioavailable testosterone), and sex hormone-binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Age-adjusted linear regression models were used to determine the association between the SNPs in an additive genetic model and log-transformed biomarker levels. RESULTS: Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P < 1.1 x 10(-3)) and bioavailable testosterone (P < 6.3 x 10(-4)). Suggestive associations were seen for a cluster of nine SNPs in prostate cancer risk region 1 and androstenedione (P < 0.05). CONCLUSIONS: These preliminary findings require confirmation in larger studies but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions might correlate with androgen levels. IMPACT: These results might provide some clues for the strong link between 8q24 and prostate cancer risk.
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: Christopher A Haiman; Nick Patterson; Matthew L Freedman; Simon R Myers; Malcolm C Pike; Alicja Waliszewska; Julie Neubauer; Arti Tandon; Christine Schirmer; Gavin J McDonald; Steven C Greenway; Daniel O Stram; Loic Le Marchand; Laurence N Kolonel; Melissa Frasco; David Wong; Loreall C Pooler; Kristin Ardlie; Ingrid Oakley-Girvan; Alice S Whittemore; Kathleen A Cooney; Esther M John; Sue A Ingles; David Altshuler; Brian E Henderson; David Reich Journal: Nat Genet Date: 2007-04-01 Impact factor: 38.330
Authors: Julius Gudmundsson; Patrick Sulem; Andrei Manolescu; Laufey T Amundadottir; Daniel Gudbjartsson; Agnar Helgason; Thorunn Rafnar; Jon T Bergthorsson; Bjarni A Agnarsson; Adam Baker; Asgeir Sigurdsson; Kristrun R Benediktsdottir; Margret Jakobsdottir; Jianfeng Xu; Thorarinn Blondal; Jelena Kostic; Jielin Sun; Shyamali Ghosh; Simon N Stacey; Magali Mouy; Jona Saemundsdottir; Valgerdur M Backman; Kristleifur Kristjansson; Alejandro Tres; Alan W Partin; Marjo T Albers-Akkers; Javier Godino-Ivan Marcos; Patrick C Walsh; Dorine W Swinkels; Sebastian Navarrete; Sarah D Isaacs; Katja K Aben; Theresa Graif; John Cashy; Manuel Ruiz-Echarri; Kathleen E Wiley; Brian K Suarez; J Alfred Witjes; Mike Frigge; Carole Ober; Eirikur Jonsson; Gudmundur V Einarsson; Jose I Mayordomo; Lambertus A Kiemeney; William B Isaacs; William J Catalona; Rosa B Barkardottir; Jeffrey R Gulcher; Unnur Thorsteinsdottir; Augustine Kong; Kari Stefansson Journal: Nat Genet Date: 2007-04-01 Impact factor: 38.330
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: P C Prorok; G L Andriole; R S Bresalier; S S Buys; D Chia; E D Crawford; R Fogel; E P Gelmann; F Gilbert; M A Hasson; R B Hayes; C C Johnson; J S Mandel; A Oberman; B O'Brien; M M Oken; S Rafla; D Reding; W Rutt; J L Weissfeld; L Yokochi; J K Gohagan Journal: Control Clin Trials Date: 2000-12
Authors: Meredith Yeager; Nilanjan Chatterjee; Julia Ciampa; Kevin B Jacobs; Jesus Gonzalez-Bosquet; Richard B Hayes; Peter Kraft; Sholom Wacholder; Nick Orr; Sonja Berndt; Kai Yu; Amy Hutchinson; Zhaoming Wang; Laufey Amundadottir; Heather Spencer Feigelson; Michael J Thun; W Ryan Diver; Demetrius Albanes; Jarmo Virtamo; Stephanie Weinstein; Fredrick R Schumacher; Geraldine Cancel-Tassin; Olivier Cussenot; Antoine Valeri; Gerald L Andriole; E David Crawford; Christopher A Haiman; Brian Henderson; Laurence Kolonel; Loic Le Marchand; Afshan Siddiq; Elio Riboli; Timothy J Key; Rudolf Kaaks; William Isaacs; Sarah Isaacs; Kathleen E Wiley; Henrik Gronberg; Fredrik Wiklund; Pär Stattin; Jianfeng Xu; S Lilly Zheng; Jielin Sun; Lars J Vatten; Kristian Hveem; Merethe Kumle; Margaret Tucker; Daniela S Gerhard; Robert N Hoover; Joseph F Fraumeni; David J Hunter; Gilles Thomas; Stephen J Chanock Journal: Nat Genet Date: 2009-09-20 Impact factor: 38.330
Authors: Heba S Omar; Olfat G Shaker; Yasser H Nassar; Samar A Marzouk; Mohamed S ElMarzouky Journal: Mol Cell Biochem Date: 2015-02-28 Impact factor: 3.396
Authors: Konstantinos K Tsilidis; Ruth C Travis; Paul N Appleby; Naomi E Allen; Sara Lindstrom; Fredrick R Schumacher; David Cox; Ann W Hsing; Jing Ma; Gianluca Severi; Demetrius Albanes; Jarmo Virtamo; Heiner Boeing; H Bas Bueno-de-Mesquita; Mattias Johansson; J Ramón Quirós; Elio Riboli; Afshan Siddiq; Anne Tjønneland; Dimitrios Trichopoulos; Rosario Tumino; J Michael Gaziano; Edward Giovannucci; David J Hunter; Peter Kraft; Meir J Stampfer; Graham G Giles; Gerald L Andriole; Sonja I Berndt; Stephen J Chanock; Richard B Hayes; Timothy J Key Journal: Am J Epidemiol Date: 2012-03-29 Impact factor: 4.897
Authors: Jasmin Teresa Ney; Ingolf Juhasz-Boess; Frank Gruenhage; Stefan Graeber; Rainer Maria Bohle; Michael Pfreundschuh; Erich Franz Solomayer; Gunter Assmann Journal: BMC Cancer Date: 2013-01-31 Impact factor: 4.430