Prostate Cancer Susceptibility in Men of African Ancestry at 8q24

JNCI: Journal of the National Cancer Institute, Jul 2016

The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8–128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10 –8 , all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10 –40 ; rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10 –27 ; and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10 –13 ). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer–associated long noncoding RNAs (lncRNAs), including PRNCR1 , PCAT1, and PCAT2 . These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.

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Prostate Cancer Susceptibility in Men of African Ancestry at 8q24

JNCI J Natl Cancer Inst ( Prostate C ancer S usceptibility in M en of African A ncestry at 8q24 A. Rand 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Dennis J. Hazelett 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Sue A. Ingles 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Janet L. Stanford 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Wei Zheng 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Fredrick 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 R. Schumacher 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Sonja I. Berndt 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Zhaoming Wang 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Jianfeng Xu 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Nadin Rohland 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 David Reich 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Arti Tandon 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Dimple Notani 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Michael G. Rosenfeld 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Ranveer Singh Jayani 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Suzanne Kolb 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Susan 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 M. Gapstur 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Victoria L. Stevens 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Curtis A. Pettaway 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Edward 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 D. Yeboah 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Yao Tettey 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Richard 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 B. Biritwum 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Andrew 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 A. Adjei 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Evelyn Tay 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Ann Truelove 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Shelley Niwa 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Anand 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 P. Chokkalingam 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Esther 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 M. John 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 B. Murphy 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 B. Signorello 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 John Carpten 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 M. Cristina Leske 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Suh-Yuh Wu 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Anslem J. M. Hennis 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Christine Neslund-Dudas 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Phyllis J. Goodman 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 A. Klein 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 S. Lilly Zheng 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Alex Lubwama 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Loreall C. Pooler 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Xin Sheng 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Gerhard 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Michael B. Cook 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Stephen J. Chanock 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Daniel O. Stram 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Stephen Watya 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 William J. Blot 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 David 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 V. Conti 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Brian 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD (WBI); Division of Public Health Sciences (JLS, SK) and SWOG Statistical Center (PJG), 0 David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, CA (BP); Howard Hughes Medical Institute, Department of Medicine, School of , USA 1 , Christopher 2 Affiliations of authors: Department of Preventive Medicine (YH , KAR, DJH, SAI, FRS, GC, LCP, XS, GAC, DOS, DVC, BEH , CAH) and Department of Urology (GAC) , Keck 3 E. Henderso n 4 Broad Institute of MIT and Harvard , Cambridge, MA (NR, DR, AT, AA, DQ , SM); Department of Pathology and Laboratory Medicine and Department of Human Genetics 5 Bu Teaching Hospital , Accra, Ghana (EDY, YT, RBB, AAA , ET); University of Ghana Medical School , Accra, Ghana (EDY, YT, RBB, AAA, ET); Westat, Rockville, MD (AT , USA 6 Bogdan Pasaniuc , Alex Allen, Dominique Quinque, Swapan Mallick 7 Medicine, University of California , San Diego, San Diego, CA (DN, MGR , RSJ); Epidemiology Research Program, American Cancer Society , Atlanta, GA (SMG, VLS); Korle , USA 8 The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions , please 9 of Health Sciences , Kampala, Uganda (AL, SW); Uro Ca (...truncated)


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Han, Ying, Rand, Kristin A., Hazelett, Dennis J., Ingles, Sue A., Kittles, Rick A., Strom, Sara S., Rybicki, Benjamin A., Nemesure, Barbara, Isaacs, William B., Stanford, Janet L., Zheng, Wei, Schumacher, Fredrick R., Berndt, Sonja I., Wang, Zhaoming, Xu, Jianfeng, Rohland, Nadin, Reich, David, Tandon, Arti, Pasaniuc, Bogdan, Allen, Alex, Quinque, Dominique, Mallick, Swapan, Notani, Dimple, Rosenfeld, Michael G., Jayani, Ranveer Singh, Kolb, Suzanne, Gapstur, Susan M., Stevens, Victoria L., Pettaway, Curtis A., Yeboah, Edward D., Tettey, Yao, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Chokkalingam, Anand P., John, Esther M., Murphy, Adam B., Signorello, Lisa B., Carpten, John, Leske, M. Cristina, Wu, Suh-Yuh, Hennis, Anslem J. M., Neslund-Dudas, Christine, Hsing, Ann W., Chu, Lisa, Goodman, Phyllis J., Klein, Eric A., Zheng, S. Lilly, Witte, John S., Casey, Graham, Lubwama, Alex, Pooler, Loreall C., Sheng, Xin, Coetzee, Gerhard A., Cook, Michael B., Chanock, Stephen J., Stram, Daniel O., Watya, Stephen, Blot, William J., Conti, David V., Henderson, Brian E., Haiman, Christopher A.. Prostate Cancer Susceptibility in Men of African Ancestry at 8q24, JNCI: Journal of the National Cancer Institute, 2016, Volume 108, Issue 7, DOI: 10.1093/jnci/djv431