Childhood, adolescent, and young adulthood cancer risk in BRCA1 or BRCA2 pathogenic variant carriers
Authors: Li Shuai , Madanat-Harjuoja Laura , Leslie Goska , Barnes Daniel R , Bolla Manjeet K , Dennis Joe , Parsons Michael T , Apostolou Paraskevi , Arnold Norbert , Bosse Kristin ,   EMBRACE Collaborators, Ahmed Munaza , Barwell Julian , Brady Angela , Brennan Paul , Conti Hector , Cook Jackie , Copeland Harriet , Davidson Rosemarie , Donaldson Alan , Evans D Gareth , Gallagher David , Hart Rachel , Izatt Louise , Kanani Farah , Kemp Zoe , Lalloo Fiona , Miedzybrodzka Zosia , Morrison Patrick , Murray Alex , Murray Jennie , Musgrave Hannah , Ong Kai-Ren , Rodgers Mark , Searle Claire , Side Lucy , Snape Katie , Tischkowitz Marc , Tripathi Vishakha , Walker Lisa , Cook Jackie , Engel Christoph , Evans D Gareth , Fostira Florentia , Frone Megan N , Gehrig Andrea , Greene Mark H , Hackmann Karl , Hahnen Eric , Harbeck Nadia , Hauke Jan , Hentschel Julia , Horvath Judit , Izatt Louise , Kiechle Marion , Konstantopoulou Irene , Lalloo Fiona , Ngeow Joanne , Niederacher Dieter , Ritter Julia , Santamariña Marta , Schmutzler Rita K , Searle Claire , Sutter Christian , Tischkowitz Marc , Tripathi Vishakha , Vega Ana , Wallaschek Hannah , Wang-Gohrke Shan , Wappenschmidt Barbara , Weber Bernhard H F , Yannoukakos Drakoulis , Zhao Emily , Easton Douglas F , Antoniou Antonis C , Chenevix-Trench Georgia , Rebbeck Timothy R , Diller Lisa R 
Published: November 2024

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 &lt; 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.