Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women.
Journal
Journal of the National Cancer Institute
ISSN: 1460-2105
Titre abrégé: J Natl Cancer Inst
Pays: United States
ID NLM: 7503089
Informations de publication
Date de publication:
14 12 2020
14 12 2020
Historique:
received:
05
11
2019
revised:
27
01
2020
accepted:
23
03
2020
pubmed:
20
5
2020
medline:
29
4
2021
entrez:
20
5
2020
Statut:
ppublish
Résumé
The risks of breast cancer in African American (AA) women associated with inherited mutations in breast cancer predisposition genes are not well defined. Thus, whether multigene germline hereditary cancer testing panels are applicable to this population is unknown. We assessed associations between mutations in panel-based genes and breast cancer risk in 5054 AA women with breast cancer and 4993 unaffected AA women drawn from 10 epidemiologic studies. Germline DNA samples were sequenced for mutations in 23 cancer predisposition genes using a QIAseq multiplex amplicon panel. Prevalence of mutations and odds ratios (ORs) for associations with breast cancer risk were estimated with adjustment for study design, age, and family history of breast cancer. Pathogenic mutations were identified in 10.3% of women with estrogen receptor (ER)-negative breast cancer, 5.2% of women with ER-positive breast cancer, and 2.3% of unaffected women. Mutations in BRCA1, BRCA2, and PALB2 were associated with high risks of breast cancer (OR = 47.55, 95% confidence interval [CI] = 10.43 to >100; OR = 7.25, 95% CI = 4.07 to 14.12; OR = 8.54, 95% CI = 3.67 to 24.95, respectively). RAD51D mutations were associated with high risk of ER-negative disease (OR = 7.82, 95% CI = 1.61 to 57.42). Moderate risks were observed for CHEK2, ATM, ERCC3, and FANCC mutations with ER-positive cancer, and RECQL mutations with all breast cancer. The study identifies genes that predispose to breast cancer in the AA population, demonstrates the validity of current breast cancer testing panels for use in AA women, and provides a basis for increased referral of AA patients for cancer genetic testing.
Sections du résumé
BACKGROUND
The risks of breast cancer in African American (AA) women associated with inherited mutations in breast cancer predisposition genes are not well defined. Thus, whether multigene germline hereditary cancer testing panels are applicable to this population is unknown. We assessed associations between mutations in panel-based genes and breast cancer risk in 5054 AA women with breast cancer and 4993 unaffected AA women drawn from 10 epidemiologic studies.
METHODS
Germline DNA samples were sequenced for mutations in 23 cancer predisposition genes using a QIAseq multiplex amplicon panel. Prevalence of mutations and odds ratios (ORs) for associations with breast cancer risk were estimated with adjustment for study design, age, and family history of breast cancer.
RESULTS
Pathogenic mutations were identified in 10.3% of women with estrogen receptor (ER)-negative breast cancer, 5.2% of women with ER-positive breast cancer, and 2.3% of unaffected women. Mutations in BRCA1, BRCA2, and PALB2 were associated with high risks of breast cancer (OR = 47.55, 95% confidence interval [CI] = 10.43 to >100; OR = 7.25, 95% CI = 4.07 to 14.12; OR = 8.54, 95% CI = 3.67 to 24.95, respectively). RAD51D mutations were associated with high risk of ER-negative disease (OR = 7.82, 95% CI = 1.61 to 57.42). Moderate risks were observed for CHEK2, ATM, ERCC3, and FANCC mutations with ER-positive cancer, and RECQL mutations with all breast cancer.
CONCLUSIONS
The study identifies genes that predispose to breast cancer in the AA population, demonstrates the validity of current breast cancer testing panels for use in AA women, and provides a basis for increased referral of AA patients for cancer genetic testing.
Identifiants
pubmed: 32427313
pii: 5838706
doi: 10.1093/jnci/djaa040
pmc: PMC7735769
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1213-1221Subventions
Organisme : NCI NIH HHS
ID : R01 CA225662
Pays : United States
Organisme : NCI NIH HHS
ID : K01 CA212056
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA047147
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164974
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA204819
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA100598
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA151135
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA098663
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA192393
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014520
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA067264
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164973
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA116201
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164920
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199277
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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