Li, Shuai and Madanat-Harjuoja, Laura and Leslie, Goska and Barnes, Daniel R. and Bolla, Manjeet K. and Dennis, Joe and Parsons, Michael T. and Apostolou, Paraskevi and Arnold, Norbert and Bosse, Kristin and Ahmed, Munaza and Barwell, Julian and Brady, Angela and Brennan, Paul and Conti, Hector and Cook, Jackie and Engel, Christoph and Evans, D. Gareth and Fostira, Florentia and Frone, Megan N. and Gehrig, Andrea and Greene, Mark H. and Hackmann, Karl and Hahnen, Eric and Harbeck, Nadia and Hauke, Jan and Hentschel, Julia and Horvath, Judit and Izatt, Louise and Kiechle, Marion and Konstantopoulou, Irene and Lalloo, Fiona and Ngeow, Joanne and Niederacher, Dieter and Ritter, Julia and Santamarina, Marta and Schmutzler, Rita K. and Searle, Claire and Sutter, Christian and Tischkowitz, Marc and Tripathi, Vishakha and Vega, Ana and Wallaschek, Hannah and Wang-Gohrke, Shan and Wappenschmidt, Barbara and Weber, Bernhard H. F. and Yannoukakos, Drakoulis and Zhao, Emily and Easton, Douglas F. and Antoniou, Antonis C. and Chenevix-Trench, Georgia and Rebbeck, Timothy R. and Diller, Lisa R. (2025) Childhood, adolescent, and young adulthood cancer risk in BRCA1 or BRCA2 pathogenic variant carriers. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 117 (4). pp. 728-736. ISSN 0027-8874, 1460-2105
Full text not available from this repository. (Request a copy)Abstract
Background: Whether carriers of BRCA1 or BRCA2 pathogenic variants have increased risks of childhood, adolescent, and young adult cancers is controversial. We aimed to evaluate this risk and to inform clinical care of young BRCA1 and BRCA2 pathogenic variant carriers and genetic testing for childhood, adolescent, and young adult cancer patients. Methods: Using data from 47 117 individuals from 3086 BRCA1 or BRCA2 families, we conducted pedigree analysis to estimate relative risks (RRs) for cancers diagnosed before age 30 years. Results: Our data included 274 cancers diagnosed before age 30 years: 139 breast cancers, 10 ovarian cancers, and 125 nonbreast nonovarian cancers. Associations for breast cancer in young adulthood (aged 20-29 years) were found with relative risks of 11.4 (95% confidence interval [CI] = 5.5 to 23.7) and 5.2 (95% CI = 1.6 to 17.7) for BRCA1 and BRCA2 pathogenic variant carriers, respectively. No association was found for any other investigated childhood, adolescent, and young adult cancer or for all nonbreast nonovarian cancers combined; the relative risks were 0.4 (95% CI = 0.1 to 1.4) and 1.4 (95% CI = 0.7 to 3.0) in BRCA1 and BRCA2 pathogenic variant carriers, respectively. Conclusion: We found no evidence that BRCA1 and BRCA2 pathogenic variant carriers have an increased childhood, adolescent, and young adult cancer risk aside from breast cancer in women aged between 20 and 30 years. Our results, along with a critical evaluation of previous germline sequencing studies, suggest that the childhood and adolescent cancer risk conferred by BRCA1 and BRCA2 pathogenic variant would be low (ie, RR < 2) if it existed. Our findings do not support pathogenic variant testing for offspring of BRCA1 and BRCA2 pathogenic variant carriers at ages younger than 18 years or for conducting BRCA1 and BRCA2 pathogenic variant testing for childhood and adolescent cancer patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ASCERTAINMENT SAMPLING PROBLEM; BREAST-CANCER; FAMILY-HISTORY; GERMLINE MUTATIONS; PREDISPOSITION; SUSCEPTIBILITY; RESOLUTION; OVARIAN; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Mar 2026 07:30 |
| Last Modified: | 27 Mar 2026 07:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67955 |
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