Ji Chen, Ge Wenjing, Zhu Chen, Shen Fang, Yu Yuhui, Pang Guanlian, Li Qiao, Zhu Mingxuan, Ma Zhimin, Zhu Xia, Fu Yating, Gong Linnan, Wang Tianpei, Du Lingbin, Jin Guangfu, Zhu Meng
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Nanjing Medical University, Nanjing, China.
Int J Cancer. 2025 Feb 1;156(3):505-517. doi: 10.1002/ijc.35187. Epub 2024 Sep 18.
Family history (FH) of cancer and polygenic risk scores (PRS) are pivotal for cancer risk assessment, yet their combined impact remains unclear. Participants in the UK Biobank (UKB) were recruited between 2006 and 2010, with complete follow-up data updated until February 2020 for Scotland and January 2021 for England and Wales. Using UKB data (N = 442,399), we constructed PRS and incidence-weighted overall cancer PRS (CPRS). FH was assessed through self-reported standardized questions. Among 202,801 men (34.6% with FH) and 239,598 women (42.0% with FH), Cox regression was used to examine the associations between FH, PRS, and cancer risk. We found a significant dose-response relationship between FH of cancer and corresponding cancer risk (P < .05), with over 10 significant pairs of cross-cancer effects of FH. FH and PRS are positively correlated and independent. Joint effects of FH of cancer (multiple cancers) and PRS (CPRS) on corresponding cancer risk were observed: for instance, compared with participants with no FH of cancer and low PRS, men with FH of cancer and high PRS had the highest risk of colorectal cancer (hazard ratio [HR]: 3.69, 95% confidence interval [CI]: 3.01-4.52). Additive interactions were observed in prostate and overall cancer risk for men and breast cancer for women, with the most significant result being a relative excess risk of interaction (RERI) of 2.98, accounting for ~34% of the prostate cancer risk. In conclusion, FH and PRS collectively contribute to cancer risk, supporting their combined application in personalized risk assessment and early intervention strategies.
癌症家族史（FH）和多基因风险评分（PRS）对癌症风险评估至关重要，但其联合影响仍不明确。英国生物银行（UKB）的参与者于2006年至2010年招募，苏格兰的完整随访数据更新至2020年2月，英格兰和威尔士的更新至2021年1月。利用UKB数据（N = 442,399），我们构建了PRS和发病率加权的总体癌症PRS（CPRS）。FH通过自我报告的标准化问题进行评估。在202,801名男性（34.6%有FH）和239,598名女性（42.0%有FH）中，采用Cox回归来检验FH、PRS与癌症风险之间的关联。我们发现癌症FH与相应癌症风险之间存在显著的剂量反应关系（P < 0.05），有超过10对显著的FH跨癌症效应。FH和PRS呈正相关且相互独立。观察到癌症FH（多种癌症）和PRS（CPRS）对相应癌症风险的联合效应：例如，与无癌症FH且PRS低的参与者相比，有癌症FH且PRS高的男性患结直肠癌的风险最高（风险比[HR]：3.69，95%置信区间[CI]：3.01 - 4.52）。在男性的前列腺癌和总体癌症风险以及女性的乳腺癌风险中观察到相加交互作用，最显著的结果是交互作用的相对超额风险（RERI）为2.98，约占前列腺癌风险的34%。总之，FH和PRS共同影响癌症风险，支持它们在个性化风险评估和早期干预策略中的联合应用。
