美国南加州大学Christopher A. Haiman等多个研究团队共同合作，近期取得重要工作进展。他们通过多祖先全基因组分析，发现了187种新风险变异来表征前列腺癌的风险。相关研究成果2023年11月9日在线发表于《自然—遗传学》杂志上。

据介绍，遗传风险评分（GRS）在不同人群中的可转移性和临床价值仍然有限，这是由于不同祖先群体之间的遗传研究不平衡。

研究人员对156319例癌症前列腺病例和788443例欧洲、非洲、亚洲和西班牙裔男性对照进行了一项多血统全基因组关联研究，反映出非欧洲病例数比之前的癌症全基因组关联研究增加了57%。研究人员确定了187种新的前列腺癌症风险变异，使风险变异总数增加到451种。外部复制的多血统GRS与风险相关，从非洲血统男性的1.8（每标准差）到欧洲血统男性的2.2。在非洲血统的男性中，GRS与更大的侵袭性疾病风险相关（P = 0.03）。

总之，这一研究提出了新的前列腺癌易感基因座和一种有效的跨祖先群体风险分层的GRS。

附：英文原文

Title: Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

Author: Wang, Anqi, Shen, Jiayi, Rodriguez, Alex A., Saunders, Edward J., Chen, Fei, Janivara, Rohini, Darst, Burcu F., Sheng, Xin, Xu, Yili, Chou, Alisha J., Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Plym, Anna, Sahimi, Ali, Hoffman, Thomas J., Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Laisk, Triin, Figuerdo, Jssica, Muir, Kenneth, Ito, Shuji, Liu, Xiaoxi, Uchio, Yuji, Kubo, Michiaki, Kamatani, Yoichiro, Lophatananon, Artitaya, Wan, Peggy, Andrews, Caroline, Lori, Adriana, Choudhury, Parichoy P., Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Rentsch, Christopher T., Cho, Kelly, Mcmahon, Benjamin H., Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Borge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Rder, Andreas, Stroomberg, Hein V., Batra, Jyotsna, Chambers, Suzanne, Horvath, Lisa, Clements, Judith A., Tilly, Wayne, Risbridger, Gail P.

Issue&Volume: 2023-11-09

Abstract: The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups. A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.

DOI: 10.1038/s41588-023-01534-4

Source: https://www.nature.com/articles/s41588-023-01534-4