Shuai Li, Laura Madanat-Harjuoja, Goska Leslie, Daniel R Barnes, Manjeet K Bolla, Joe Dennis, Michael T Parsons, Paraskevi Apostolou, Norbert Arnold, Kristin Bosse, Antonis C Antoniou On Behalf Of Embrace Collaborators, Jackie Cook, Christoph Engel, D Gareth Evans, Florentia Fostira, Megan N Frone, Andrea Gehrig, Mark H Greene, Karl Hackmann, Eric Hahnen, Nadia Harbeck, Jan Hauke, Julia Hentschel, Judit Horvath, Louise Izatt, Marion Kiechle, Irene Konstantopoulou, Fiona Lalloo, Joanne Ngeow Yuen Yie, Dieter Niederacher, Julia Ritter, Marta Santamariña, Rita K Schmutzler, Claire Searle, Christian Sutter, Marc Tischkowitz, Vishakha Tripathi, Ana Vega, Hannah Wallaschek, Shan Wang-Gohrke, Barbara Wappenschmidt, Bernhard H F Weber, Drakoulis Yannoukakos, Emily Zhao, Douglas F Easton, Antonis C Antoniou, Georgia Chenevix-Trench, Timothy R Rebbeck, Lisa R Diller
{"title":"Childhood, adolescent and young adulthood cancer risk in BRCA1 or BRCA2 pathogenic variant carriers.","authors":"Shuai Li, Laura Madanat-Harjuoja, Goska Leslie, Daniel R Barnes, Manjeet K Bolla, Joe Dennis, Michael T Parsons, Paraskevi Apostolou, Norbert Arnold, Kristin Bosse, Antonis C Antoniou On Behalf Of Embrace Collaborators, Jackie Cook, Christoph Engel, D Gareth Evans, Florentia Fostira, Megan N Frone, Andrea Gehrig, Mark H Greene, Karl Hackmann, Eric Hahnen, Nadia Harbeck, Jan Hauke, Julia Hentschel, Judit Horvath, Louise Izatt, Marion Kiechle, Irene Konstantopoulou, Fiona Lalloo, Joanne Ngeow Yuen Yie, Dieter Niederacher, Julia Ritter, Marta Santamariña, Rita K Schmutzler, Claire Searle, Christian Sutter, Marc Tischkowitz, Vishakha Tripathi, Ana Vega, Hannah Wallaschek, Shan Wang-Gohrke, Barbara Wappenschmidt, Bernhard H F Weber, Drakoulis Yannoukakos, Emily Zhao, Douglas F Easton, Antonis C Antoniou, Georgia Chenevix-Trench, Timothy R Rebbeck, Lisa R Diller","doi":"10.1093/jnci/djae306","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Whether carriers of BRCA1 or BRCA2 (BRCA1/2) pathogenic variants (PVs) have increased risks of childhood, adolescent, and young adult (CAYA) cancers is controversial. We aimed to evaluate this risk and to inform clinical care of young BRCA1/2 PV carriers and genetic testing for CAYA cancer patients.</p><p><strong>Methods: </strong>Using data from 47,117 individuals from 3,086 BRCA1/2 families, we conducted pedigree analysis to estimate relative risks (RRs) for cancers diagnosed before age 30.</p><p><strong>Results: </strong>Our data included 274 cancers diagnosed before age 30: 139 breast cancers, 10 ovarian cancers, and 125 non-breast non-ovarian cancers. Associations for breast cancer in young adulthood (20-29 years) were found with RRs of 11.4 (95% CI: 5.5, 23.7) and 5.2 (95% CI: 1.6, 17.7) for BRCA1 and BRCA2 PV carriers, respectively. No association was found for any other investigated CAYA cancer, nor for all non-breast non-ovarian cancers combined: the RRs were 0.4 (95% CI: 0.1, 1.4) and 1.4 (95% CI: 0.7, 3.0) in BRCA1 or BRCA2 PV carriers, respectively.</p><p><strong>Conclusion: </strong>We found no evidence that BRCA1/2 PV carriers have an increased CAYA cancer risk aside from breast cancer in women in their 20's. Our results, along with a critical evaluation of previous germline sequencing studies, suggest that the childhood and adolescent cancer risk conferred by BRCA1/2 PV would be low (ie, RR < 2) if it existed. Our findings do not support PV testing for offspring of BRCA1/2 PV carriers at ages <18 years, nor for conducting BRCA1/2 PV testing for childhood and adolescent cancer patients.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9000,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JNCI Journal of the National Cancer Institute","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jnci/djae306","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Whether carriers of BRCA1 or BRCA2 (BRCA1/2) pathogenic variants (PVs) have increased risks of childhood, adolescent, and young adult (CAYA) cancers is controversial. We aimed to evaluate this risk and to inform clinical care of young BRCA1/2 PV carriers and genetic testing for CAYA cancer patients.
Methods: Using data from 47,117 individuals from 3,086 BRCA1/2 families, we conducted pedigree analysis to estimate relative risks (RRs) for cancers diagnosed before age 30.
Results: Our data included 274 cancers diagnosed before age 30: 139 breast cancers, 10 ovarian cancers, and 125 non-breast non-ovarian cancers. Associations for breast cancer in young adulthood (20-29 years) were found with RRs of 11.4 (95% CI: 5.5, 23.7) and 5.2 (95% CI: 1.6, 17.7) for BRCA1 and BRCA2 PV carriers, respectively. No association was found for any other investigated CAYA cancer, nor for all non-breast non-ovarian cancers combined: the RRs were 0.4 (95% CI: 0.1, 1.4) and 1.4 (95% CI: 0.7, 3.0) in BRCA1 or BRCA2 PV carriers, respectively.
Conclusion: We found no evidence that BRCA1/2 PV carriers have an increased CAYA cancer risk aside from breast cancer in women in their 20's. Our results, along with a critical evaluation of previous germline sequencing studies, suggest that the childhood and adolescent cancer risk conferred by BRCA1/2 PV would be low (ie, RR < 2) if it existed. Our findings do not support PV testing for offspring of BRCA1/2 PV carriers at ages <18 years, nor for conducting BRCA1/2 PV testing for childhood and adolescent cancer patients.
期刊介绍:
The Journal of the National Cancer Institute is a reputable publication that undergoes a peer-review process. It is available in both print (ISSN: 0027-8874) and online (ISSN: 1460-2105) formats, with 12 issues released annually. The journal's primary aim is to disseminate innovative and important discoveries in the field of cancer research, with specific emphasis on clinical, epidemiologic, behavioral, and health outcomes studies. Authors are encouraged to submit reviews, minireviews, and commentaries. The journal ensures that submitted manuscripts undergo a rigorous and expedited review to publish scientifically and medically significant findings in a timely manner.