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Family history and genetic risk score combined to guide cancer risk stratification: A prospective cohort study

医学 前列腺癌 癌症 结直肠癌 内科学 危险系数 家族史 置信区间 乳腺癌 肿瘤科 前瞻性队列研究 队列 癌症登记处 相对风险 人口学 社会学
作者
Ji Chen,Wenjing Ge,Chen Zhu,Fang Shen,Yuhui Yu,Guanlian Pang,Qiao Li,Mingxuan Zhu,Zhimin Ma,Xia Zhu,Yating Fu,Linnan Gong,Tianpei Wang,Lingbin Du,Guangfu Jin,Meng Zhu
出处
期刊:International Journal of Cancer [Wiley]
标识
DOI:10.1002/ijc.35187
摘要

Abstract 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 trend < .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.
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