Spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer: Screening of 16,501 unselected patients with breast cancer and 5890 controls by next-generation sequencing.
Adult
BRCA1 Protein
/ genetics
BRCA2 Protein
/ genetics
Case-Control Studies
China
/ epidemiology
Cohort Studies
Early Detection of Cancer
Fanconi Anemia Complementation Group N Protein
/ genetics
Female
Gene Frequency
Genes, BRCA1
Genes, BRCA2
Genetic Predisposition to Disease
Germ-Line Mutation
High-Throughput Nucleotide Sequencing
/ methods
Humans
Mass Screening
/ methods
Prevalence
Risk
Sequence Analysis, DNA
Triple Negative Breast Neoplasms
/ epidemiology
breast cancer risk
clinical characteristics
germline mutation
next-generation sequencing
partner and localizer BRCA2 (PALB2)
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
15 07 2020
15 07 2020
Historique:
received:
22
11
2019
revised:
08
03
2020
accepted:
19
03
2020
pubmed:
28
4
2020
medline:
21
5
2021
entrez:
28
4
2020
Statut:
ppublish
Résumé
Partner and localizer BRCA2 (PALB2) is a breast cancer predisposition gene, but the clinical relevance of PALB2 germline mutations in Chinese patients with breast cancer remains unknown. This study attempted to investigate the full prevalence and spectrum of PALB2 germline mutations in China and the associations between PALB2 germline mutations and breast cancer risk. A total of 21,216 unselected patients with breast cancer were enrolled from 10 provinces in China, and 5890 Chinese women without cancer were enrolled as healthy controls. PALB2 screening was based on next-generation sequencing. A total of 16,501 BRCA1/2-negative patients with breast cancer were analyzed. Deleterious PALB2 mutation carriers accounted for 0.97% (n = 160) in the breast cancer cohort and for 0.19% (n = 11) in the healthy control cohort. Forty-one novel PALB2 germline mutations were identified. A high frequency of PALB2 c.751C>T was detected, and it accounted for 10.63% of the PALB2 germline mutations detected (17 of 160). PALB2 mutations were significantly associated with increased breast cancer risk (odds ratio [OR], 5.23; 95% confidence interval [CI], 2.84-9.65; P < .0001), especially among women 30 years old or younger (OR, 10.09; 95% CI, 3.95-25.79; P < .0001). Clinical characteristics, including a family history, bigger tumor size, triple-negative breast cancer, positive lymph nodes, and bilateral breast cancer, were closely related to PALB2 mutations. This study revealed a comprehensive spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer in China. PALB2 germline mutations confer a moderately increased risk for breast cancer but profoundly increase breast cancer risk for those 30 years old or younger in the Chinese population.
Sections du résumé
BACKGROUND
Partner and localizer BRCA2 (PALB2) is a breast cancer predisposition gene, but the clinical relevance of PALB2 germline mutations in Chinese patients with breast cancer remains unknown. This study attempted to investigate the full prevalence and spectrum of PALB2 germline mutations in China and the associations between PALB2 germline mutations and breast cancer risk.
METHODS
A total of 21,216 unselected patients with breast cancer were enrolled from 10 provinces in China, and 5890 Chinese women without cancer were enrolled as healthy controls. PALB2 screening was based on next-generation sequencing.
RESULTS
A total of 16,501 BRCA1/2-negative patients with breast cancer were analyzed. Deleterious PALB2 mutation carriers accounted for 0.97% (n = 160) in the breast cancer cohort and for 0.19% (n = 11) in the healthy control cohort. Forty-one novel PALB2 germline mutations were identified. A high frequency of PALB2 c.751C>T was detected, and it accounted for 10.63% of the PALB2 germline mutations detected (17 of 160). PALB2 mutations were significantly associated with increased breast cancer risk (odds ratio [OR], 5.23; 95% confidence interval [CI], 2.84-9.65; P < .0001), especially among women 30 years old or younger (OR, 10.09; 95% CI, 3.95-25.79; P < .0001). Clinical characteristics, including a family history, bigger tumor size, triple-negative breast cancer, positive lymph nodes, and bilateral breast cancer, were closely related to PALB2 mutations.
CONCLUSIONS
This study revealed a comprehensive spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer in China. PALB2 germline mutations confer a moderately increased risk for breast cancer but profoundly increase breast cancer risk for those 30 years old or younger in the Chinese population.
Identifiants
pubmed: 32339256
doi: 10.1002/cncr.32905
pmc: PMC7384117
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
BRCA2 Protein
0
BRCA2 protein, human
0
Fanconi Anemia Complementation Group N Protein
0
PALB2 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3202-3208Subventions
Organisme : The Preclinical and Multi-center Basket Clinical Trial of the Multi-kinase Inhibitor TT-00420
ID : 2019ZX09301158
Organisme : Fundamental Research Funds for the Central Universities
ID : 2019FZJD009
Organisme : The Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents
ID : None
Organisme : National Natural Science Foundation of China
ID : 81702866
Organisme : Key Program of the Natural Science Foundation of Zhejiang Province
ID : LZ16H160002
Informations de copyright
© 2020 Zhejiang University School of Medicine Second Affiliated Hospital. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
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