小柯机器人

前列腺癌跨谱系全基因组荟萃分析可确定新的易感基因座并为遗传患病风险预测提供依据，这一成果由美国南加州大学诺里斯综合癌症中心Ruth C. Travis课题组经过不懈努力而取得。相关论文发表在2021年1月4日出版的《自然-遗传学》杂志上。

研究人员对前列腺癌全基因组关联研究（107,247例病例和127,006个对照）进行了多种群荟萃分析，确定了86个与前列腺癌风险独立相关的新遗传风险变体，从而使已知的风险变体总数达269个。最高遗传风险评分（GRS）与优势率相关，其从欧洲男性的5.06（95％置信区间（CI），4.84-5.29）变化至非洲男性的3.74（95％CI，3.36-4.17）。

据估计，非洲男性的平均GRS比欧洲男性高2.18倍（95％CI，2.14-2.22），而东亚男性的平均GRS则比欧洲男性低0.73倍（95％CI，0.71-0.76）。这些发现支持生殖系变异导致前列腺癌在人群中的患病风险差异，而GRS提供了个性化风险预测的方法。

据悉，前列腺癌是一种高遗传性疾病，但其在不同祖先人群中的发生率差异很大。

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

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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