前列腺癌跨譜系全基因組薈萃分析可確定新的風險基因座和預測患病風險
作者：
小柯機器人發布時間：2021/1/5 16:25:57
前列腺癌跨譜系全基因組薈萃分析可確定新的易感基因座並為遺傳患病風險預測提供依據，這一成果由美國南加州大學諾裡斯綜合癌症中心Ruth C. Travis課題組經過不懈努力而取得。相關論文發表在2021年1月4日出版的《自然-遺傳學》雜誌上。
研究人員對前列腺癌全基因組關聯研究（107,247例病例和127,006個對照）進行了多種群薈萃分析，確定了86個與前列腺癌風險獨立相關的新遺傳風險變體，從而使已知的風險變體總數達269個。最高遺傳風險評分（GRS）與優勢率相關，其從歐洲男性的5.06（95％置信區間（CI），4.84-5.29）變化至非洲男性的3.74（95％CI，3.36-4.17）。
據估計，非洲男性的平均GRS比歐洲男性高2.18倍（95％CI，2.14-2.22），而東亞男性的平均GRS則比歐洲男性低0.73倍（95％CI，0.71-0.76）。這些發現支持生殖系變異導致前列腺癌在人群中的患病風險差異，而GRS提供了個性化風險預測的方法。
據悉，前列腺癌是一種高遺傳性疾病，但其在不同祖先人群中的發生率差異很大。
附：英文原文
Title: Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
Author: David V. Conti, Burcu F. Darst, Lilit C. Moss, Edward J. Saunders, Xin Sheng, Alisha Chou, Fredrick R. Schumacher, Ali Amin Al Olama, Sara Benlloch, Tokhir Dadaev, Mark N. Brook, Ali Sahimi, Thomas J. Hoffmann, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi Fujita, Kenneth Muir, Artitaya Lophatananon, Peggy Wan, Loic Le Marchand, Lynne R. Wilkens, Victoria L. Stevens, Susan M. Gapstur, Brian D. Carter, Johanna Schleutker, Teuvo L. J. Tammela, Csilla Sipeky, Anssi Auvinen, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Cezary Cybulski, Dominika Wokoorczyk, Jan Lubiski, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Brge G. Nordestgaard, Sune F. Nielsen, Maren Weischer, Stig E. Bojesen, Martin Andreas Rder, Peter Iversen, Jyotsna Batra, Suzanne Chambers, Leire Moya, Lisa Horvath, Judith A. Clements, Wayne Tilley, Gail P. Risbridger, Henrik Gronberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordstrm, Nora Pashayan, Alison M. Dunning, Maya Ghoussaini, Ruth C. Travis
Issue&Volume: 2021-01-04
Abstract: Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84–5.29) for men of European ancestry to 3.74 (95% CI, 3.36–4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14–2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71–0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
DOI: 10.1038/s41588-020-00748-0
Source: https://www.nature.com/articles/s41588-020-00748-0