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

被引：1
作者：
Ji, Chen [1 ,2 ,3 ]
Ge, Wenjing [1 ,2 ,3 ]
Zhu, Chen [2 ,3 ,4 ,5 ]
Shen, Fang [1 ,2 ,3 ]
Yu, Yuhui [1 ,2 ,3 ]
Pang, Guanlian [1 ,2 ,3 ]
Li, Qiao [1 ,2 ,3 ]
Zhu, Mingxuan [1 ,2 ,3 ]
Ma, Zhimin [1 ,2 ,3 ]
Zhu, Xia [1 ,2 ,3 ]
Fu, Yating [1 ,2 ,3 ]
Gong, Linnan [1 ,2 ,3 ]
Wang, Tianpei [1 ,2 ,3 ]
Du, Lingbin [4 ,5 ]
Jin, Guangfu [1 ,2 ,3 ,6 ,7 ,8 ,9 ]
Zhu, Meng [1 ,2 ,3 ,6 ,8 ,9 ]
机构：
[1] Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Epidemiol, 101 Longmian Rd, Nanjing 211166, Peoples R China
[2] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatmen, Nanjing, Peoples R China
[3] Nanjing Med Univ, China Int Cooperat Ctr Environm & Human Hlth, Nanjing, Peoples R China
[4] Zhejiang Canc Hosp, Dept Canc Prevent, 1 East Banshan Rd, Hangzhou 310022, Peoples R China
[5] Chinese Acad Sci, Hangzhou Inst Med HIM, Hangzhou, Peoples R China
[6] Nanjing Med Univ, Jiangsu Canc Hosp, Affiliated Canc Hosp, Jiangsu Inst Canc Res,Jiangsu Key Lab Mol & Transl, Nanjing, Peoples R China
[7] Nanjing Med Univ, Affiliated Suzhou Hosp, Publ Hlth Inst, Gusu Sch, Suzhou, Peoples R China
[8] Nanjing Med Univ, Affiliated Wuxi Ctr Dis Control Prevent, Wuxi Ctr Dis Control & Prevent, Wuxi Med Ctr, Wuxi, Peoples R China
[9] Chinese Acad Med Sci, Res Units Cohort Study Cardiovasc Dis & Canc, Beijing, Peoples R China
来源：
INTERNATIONAL JOURNAL OF CANCER | 2025年 / 156卷 / 03期
基金：
中国国家自然科学基金;
关键词：
cancer risk stratification; cross cancer; family history; incidence-weighted overall cancer polygenic risk score; polygenic risk score; GENOME-WIDE ASSOCIATION; PROSTATE-CANCER; BREAST-CANCER; POLYGENIC RISK; SUSCEPTIBILITY LOCUS; TERT-CLPTM1L LOCUS; ONSET; PREDICTION; VARIANTS; BRCA2;
D O I：
10.1002/ijc.35187
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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 similar to 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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收藏
页码：505 / 517
页数：13
相关论文
共 54 条
[1]   Confidence intervals for measures of interaction [J].
Assmann, SF ;
Hosmer, DW ;
Lemeshow, S ;
Mundt, KA .
EPIDEMIOLOGY, 1996, 7 (03) :286-290
[2]   Variation at the TERT locus and predisposition for cancer [J].
Baird, Duncan M. .
EXPERT REVIEWS IN MOLECULAR MEDICINE, 2010, 12
[3]   Family History of Breast or Prostate Cancer and Prostate Cancer Risk [J].
Barber, Lauren ;
Gerke, Travis ;
Markt, Sarah C. ;
Peisch, Samuel F. ;
Wilson, Kathryn M. ;
Ahearn, Thomas ;
Giovannucci, Edward ;
Parmigiani, Giovanni ;
Mucci, Lorelei A. .
CLINICAL CANCER RESEARCH, 2018, 24 (23) :5910-5917
[4]   Systematic analysis of telomere length and somatic alterations in 31 cancer types [J].
Barthel, Floris P. ;
Wei, Wei ;
Tang, Ming ;
Martinez-Ledesma, Emmanuel ;
Hu, Xin ;
Amin, Samirkumar B. ;
Akdemir, Kadir C. ;
Seth, Sahil ;
Song, Xingzhi ;
Wang, Qianghu ;
Lichtenberg, Tara ;
Hu, Jian ;
Zhang, Jianhua ;
Zheng, Siyuan ;
Verhaak, Roel G. W. .
NATURE GENETICS, 2017, 49 (03) :349-357
[5]   Familial Clustering of Breast and Prostate Cancer and Risk of Postmenopausal Breast Cancer in the Women's Health Initiative Study [J].
Beebe-Dimmer, Jennifer L. ;
Yee, Cecilia ;
Cote, Michele L. ;
Petrucelli, Nancie ;
Palmer, Nynikka ;
Bock, Cathryn ;
Lane, Dorothy ;
Agalliu, Ilir ;
Stefanick, Marcia L. ;
Simon, Michael S. .
CANCER, 2015, 121 (08) :1265-1272
[6]   The UK Biobank resource with deep phenotyping and genomic data [J].
Bycroft, Clare ;
Freeman, Colin ;
Petkova, Desislava ;
Band, Gavin ;
Elliott, Lloyd T. ;
Sharp, Kevin ;
Motyer, Allan ;
Vukcevic, Damjan ;
Delaneau, Olivier ;
O'Connell, Jared ;
Cortes, Adrian ;
Welsh, Samantha ;
Young, Alan ;
Effingham, Mark ;
McVean, Gil ;
Leslie, Stephen ;
Allen, Naomi ;
Donnelly, Peter ;
Marchini, Jonathan .
NATURE, 2018, 562 (7726) :203-+
[7]   Association Between Titin Loss-of-Function Variants and Early-Onset Atrial Fibrillation [J].
Choi, Seung Hoan ;
Weng, Lu-Chen ;
Roselli, Carolina ;
Lin, Honghuang ;
Haggerty, Christopher M. ;
Shoemaker, M. Benjamin ;
Barnard, John ;
Arking, Dan E. ;
Chasman, Daniel I. ;
Albert, Christine M. ;
Chaffin, Mark ;
Tucker, Nathan R. ;
Smith, Jonathan D. ;
Gupta, Namrata ;
Gabriel, Stacey ;
Margolin, Lauren ;
Shea, Marisa A. ;
Shaffer, Christian M. ;
Yoneda, Zachary T. ;
Boerwinkle, Eric ;
Smith, Nicholas L. ;
Silverman, Edwin K. ;
Redline, Susan ;
Vasan, Ramachandran S. ;
Burchard, Esteban G. ;
Gogarten, Stephanie M. ;
Laurie, Cecelia ;
Blackwell, Thomas W. ;
Abecasis, Goncalo ;
Carey, David J. ;
Fornwalt, Brandon K. ;
Smelser, Diane T. ;
Baras, Aris ;
Dewey, Frederick E. ;
Jaquish, Cashell E. ;
Papanicolaou, George J. ;
Sotoodehnia, Nona ;
Van Wagoner, David R. ;
Psaty, Bruce M. ;
Kathiresan, Sekar ;
Darbar, Dawood ;
Alonso, Alvaro ;
Heckbert, Susan R. ;
Chung, Mina K. ;
Roden, Dan M. ;
Benjamin, Emelia J. ;
Murray, Michael F. ;
Lunetta, Kathryn L. ;
Lubitz, Steven A. ;
Ellinor, Patrick T. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2018, 320 (22) :2354-2364
[8]  
Conti D.V., 2021, NAT GENET, V53, P65
[9]   Family health history reporting is sensitive to small changes in wording [J].
Conway-Pearson, Liam S. ;
Christensen, Kurt D. ;
Savage, Sarah K. ;
Huntington, Noelle L. ;
Weitzman, Elissa R. ;
Ziniel, Sonja I. ;
Bacon, Phoebe ;
Cacioppo, Cara N. ;
Green, Robert C. ;
Holm, Ingrid A. .
GENETICS IN MEDICINE, 2016, 18 (12) :1308-1311
[10]   Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations [J].
Dai, Juncheng ;
Zhu, Meng ;
Wang, Yuzhuo ;
Qin, Na ;
Ma, Hongxia ;
He, Yong-Qiao ;
Zhang, Ruoxin ;
Tan, Wen ;
Fan, Jingyi ;
Wang, Tianpei ;
Zheng, Hong ;
Sun, Qi ;
Wang, Lijuan ;
Huang, Mingtao ;
Ge, Zijun ;
Yu, Canqing ;
Guo, Yu ;
Wang, Tong-Min ;
Wang, Jie ;
Xu, Lin ;
Wu, Weibing ;
Chen, Liang ;
Bian, Zheng ;
Walters, Robin ;
Millwood, Iona Y. ;
Li, Xi-Zhao ;
Wang, Xin ;
Hung, Rayjean J. ;
Christiani, David C. ;
Chen, Haiquan ;
Wang, Mengyun ;
Wang, Cheng ;
Jiang, Yue ;
Chen, Kexin ;
Chen, Zhengming ;
Jin, Guangfu ;
Wu, Tangchun ;
Lin, Dongxin ;
Hu, Zhibin ;
Amos, Christopher I. ;
Wu, Chen ;
Wei, Qingyi ;
Jia, Wei-Hua ;
Li, Liming ;
Shen, Hongbing .
LANCET RESPIRATORY MEDICINE, 2019, 7 (10) :881-891
123456