The risks of breast and ovarian cancer associated with the Ashkenazi Jewish founder allele BRCA2 6174delT.
BRCA2
breast neoplasm
fallopian tube neoplasm
ovarian neoplasm
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
06
12
2021
received:
18
10
2021
accepted:
08
12
2021
pubmed:
14
12
2021
medline:
23
4
2022
entrez:
13
12
2021
Statut:
ppublish
Résumé
Approximately 1% of the Ashkenazi Jewish population carries the BRCA2 6174delT (c.5946del) pathogenic variant. It is important to have accurate knowledge of the risks of breast and ovarian cancer associated with this specific variant so that women may be counseled accordingly. In this prospective study, we estimated the risks of breast and ovarian cancer associated with the 6174delT variant compared with the risks for other pathogenic variants in the BRCA2 gene. The annual risk for developing breast cancer was significantly lower in 246 women who carried the 6174delT variant compared with 721 non-Jewish women who carried a variant at any other locus in BRCA2 (1.2% per year vs. 2.4% per year, p = 0.003). We estimated the cumulative risk of breast cancer from age 30 to 70 to be 39% for carriers of the BRCA2 6174delT variant and 61% for carriers of other BRCA2 variants. The annual risk for ovarian or fallopian tube cancer was 0.51% per year for the 233 women who carried the 6174delT variant compared to 0.22% per year for the 1128 carriers of other BRCA2 variants; the difference was not significant. Lower risks for breast cancer associated with 6174delT may not impact screening and prevention choices, however, the discussion should be based on accurate risk assessment.
Substances chimiques
BRCA2 Protein
0
BRCA2 protein, human
0
Neoplasm Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
317-323Subventions
Organisme : CIHR
Pays : Canada
Organisme : Peter Gilgan Centre for Women's Cancers at Women's College Hospital, in partnership with the Canadian Cancer Society.
Informations de copyright
© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.
Références
Phelan CM, Kwan E, Jack E, et al. A low frequency of non-founder BRCA1 mutations in Ashkenazi Jewish breast-ovarian cancer families. Hum Mutat. 2002;20(5):352-357. doi:10.1002/humu.10123
Kauff ND, Perez-Segura P, Robson ME, et al. Incidence of non-founder BRCA1 and BRCA2 mutations in high risk Ashkenazi breast and ovarian cancer families. J Med Genet. 2002;39(8):611-614. doi:10.1136/jmg.39.8.611
Oddoux C, Struewing JP, Clayton CM, et al. The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1%. Nat Genet. 1996;14(2):188-190. doi:10.1038/ng1096-188
Roa BB, Boyd AA, Volcik K, Richards CS. Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet. 1996;14(2):185-187. doi:10.1038/ng1096-185
Metcalfe KA, Poll A, Royer R, et al. A comparison of the detection of BRCA mutation carriers through the provision of Jewish population-based genetic testing compared with clinic-based genetic testing. Br J Cancer. 2013;109(3):777-779. doi:10.1038/bjc.2013.309
Metcalfe KA, Poll A, Royer R, et al. Screening for founder mutations in BRCA1 and BRCA2 in unselected Jewish women. J Clin Oncol. 2010;28(3):387-391. doi:10.1200/JCO.2009.25.0712
Hu C, Hart SN, Gnanaolivu R, et al. A population-based study of genes previously implicated in breast cancer. N Engl J Med. 2021;384(5):440-451. doi:10.1056/NEJMoa2005936
Dorling L, Carvalho S, Allen J, et al. Breast cancer risk genes - association analysis in more than 113,000 women. N Engl J Med. 2021;384(5):428-439. doi:10.1056/NEJMoa1913948
National Center for Biotechnology Information. ClinVar; [VCV000009325.32]. https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000009325.32 (accessed September 23, 2021).
National Comprehensive Cancer Network. Clinical practice guidelines in oncology, genetic/familial high-risk assessment: breast, ovarian, and pancreatic; V2.2021.
Tonin P, Weber B, Offit K, et al. Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families. Nat Med. 1996;2(11):1179-1183. doi:10.1038/nm1196-1179
Antoniou AC, Pharoah PD, Narod S, et al. Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies. J Med Genet. 2005;42(7):602-603. doi:10.1136/jmg.2004.024133
Gayther SA, Mangion J, Russell P, et al. Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. Nat Genet. 1997;15(1):103-105. doi:10.1038/ng0197-103
Rebbeck TR, Mitra N, Wan F, et al. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. JAMA. 2015;313(13):1347-1361. doi:10.1001/jama.2014.5985
Thompson D, Easton D. Breast cancer linkage C. variation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am J Hum Genet. 2001;68(2):410-419. doi:10.1086/318181
Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317(23):2402-2416. doi:10.1093/jnci/djw302