Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, USA.
The Institute of Cancer Research, London, SW7 3RP, UK.
Nat Commun. 2018 Nov 5;9(1):4616. doi: 10.1038/s41467-018-06863-1.
Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62-4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.
8q24 染色体是多种癌症（包括前列腺癌）的易感位点。在这里，我们结合了来自 71535 例前列腺癌病例和 52935 例欧洲裔对照的 8q24 易感区域的遗传数据，以确定 8q24 种系变异对前列腺癌风险的总体贡献。我们确定了 12 个与前列腺癌相关的独立风险信号（p<4.28×10），其中包括三个尚未报道的风险变异。从多基因风险评分（PRS）模型中，评估 8q24 风险变异的累积效应，PRS 最高 1%的男性患前列腺癌的风险比人群平均水平高 4 倍（95%CI=3.62-4.40）。这 12 个变体解释了目前已知遗传风险因素可解释的前列腺癌家族风险的约 25%。这些发现突出了 8q24 上种系变异对前列腺癌风险的巨大影响，这对人群风险分层具有重要意义。
