Dataset Information

Evaluation of pathogenetic mutations in breast cancer predisposition genes in population-based studies conducted among Chinese women.

ABSTRACT: PURPOSE:Limited studies have been conducted to evaluate pathogenetic mutations in breast cancer predisposition genes among Chinese women. To fully characterize germline mutations of these genes in this population, we used the whole-exome sequencing data in a population-based case-control study conducted in Shanghai, China. METHODS:We evaluated exonic, splicing, and copy number variants in 11 established and 14 candidate breast cancer predisposition genes in 831 invasive breast cancer cases and 839 controls. We identified 55 pathogenic variants, including 15 newly identified in this study. RESULTS:Approximately 8% of the cases and 0.6% of the cancer-free controls carried these pathogenetic variants (P?=?3.05?×?10-15). Among cases, 3.7% had a BRCA2 pathogenic variant and 1.6% had a BRCA1 pathogenic variant, while 2.5% had a pathogenic variant in other genes including ATM, CHEK2, NBN, NF1, CDH1, PALB2, PTEN, TP53 as well as BARD1, BRIP, and RAD51D. Patients with BRCA1/2 pathogenic variants were more likely to have a family history of breast cancer and hormone receptor negative tumors compared with patients without pathogenic variants. CONCLUSIONS:This study highlighted the importance of hereditary breast cancer genes in the breast cancer etiology in this understudied population. Together with previous studies in East Asian women, this study suggested a relatively more prominent role of BRCA2 compared to BRCA1. This study also provides additional evidence to design cost-efficient genetic testing among Chinese women for risk assessment and early detection of breast cancer.

SUBMITTER: Zeng C

PROVIDER: S-EPMC7188717 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evaluation of pathogenetic mutations in breast cancer predisposition genes in population-based studies conducted among Chinese women.

Zeng Chenjie C Guo Xingyi X Wen Wanqing W Shi Jiajun J Long Jirong J Cai Qiuyin Q Shu Xiao-Ou XO Xiang Yongbin Y Zheng Wei W

Breast cancer research and treatment 20200421 2

<h4>Purpose</h4>Limited studies have been conducted to evaluate pathogenetic mutations in breast cancer predisposition genes among Chinese women. To fully characterize germline mutations of these genes in this population, we used the whole-exome sequencing data in a population-based case-control study conducted in Shanghai, China.<h4>Methods</h4>We evaluated exonic, splicing, and copy number variants in 11 established and 14 candidate breast cancer predisposition genes in 831 invasive breast can ...[more]

PMID: 32318955

Similar Datasets

Project description:African Americans have a disproportionate burden of aggressive young-onset breast cancer. Genomic testing for inherited predisposition to breast cancer is increasingly common in clinical practice, but comprehensive mutation profiles remain unknown for most minority populations. We evaluated 289 patients who self-identified as African American with primary invasive breast cancer and with personal or family cancer history or tumor characteristics associated with high genetic risk for all classes of germline mutations in known breast cancer susceptibility genes using a validated targeted capture and multiplex sequencing approach. Sixty-eight damaging germline mutations were identified in 65 (22 %, 95 % CI 18-28 %) of the 289 subjects. Proportions of patients with unequivocally damaging mutations in a breast cancer gene were 26 % (47/180; 95 % confident interval [CI] 20-33 %) of those with breast cancer diagnosis before age 45; 25 % (26/103; 95 % CI 17-35 %) of those with triple-negative breast cancer (TNBC); 29 % (45/156; 95 % CI 22-37 %) of those with a first or second degree relative with breast cancer before age 60 or with ovarian cancer; and 57 % (4/7; 95 % CI 18-90 %) of those with both breast and ovarian cancer. Of patients with mutations, 80 % (52/65) carried mutations in BRCA1 and BRCA2 genes and 20 % (13/65) carried mutations in PALB2, CHEK2, BARD1, ATM, PTEN, or TP53. The mutational allelic spectrum was highly heterogeneous, with 57 different mutations in 65 patients. Of patients meeting selection criteria other than family history (i.e., with young age at diagnosis or TNBC), 48 % (64/133) had very limited information about the history of cancer in previous generations of their families. Mutations in BRCA1 and BRCA2 or another breast cancer gene occur in one in four African American breast cancer patients with early onset disease, family history of breast or ovarian cancer, or TNBC. Each of these criteria defines patients who would benefit from genomic testing and novel therapies targeting DNA repair pathways.

Project description:ImportanceAmong Ashkenazi Jewish women, 3 mutations in BRCA1 and BRCA2 severely increase the risk of breast and ovarian cancer. However, among Ashkenazi Jewish patients with breast cancer who do not carry one of these founder mutations, the likelihood of carrying another pathogenic mutation in BRCA1 or BRCA2 or another breast cancer gene is not known. This information would be valuable to the patient and family for cancer prevention and treatment.ObjectiveTo determine the frequency of cancer-predisposing mutations other than the BRCA1 and BRCA2 founder alleles among patients of Ashkenazi Jewish ancestry with breast cancer.Design, setting, and participantsIn this cohort study, genomic DNA of women from 12 major cancer centers with a first diagnosis of invasive breast cancer who identified themselves and all 4 grandparents as Ashkenazi Jewish and participated in the New York Breast Cancer Study (NYBCS) from 1996 to 2000 was sequenced for known and candidate breast cancer genes. Data analysis was performed from July 10, 2014, to March 10, 2017.Main outcomes and measuresGenomic DNA from all 1007 NYBCS probands was sequenced for 23 known and candidate breast cancer genes using BROCA, a targeted multiplexed gene panel.ResultsOf the 1007 probands in the study, 903 probands had no founder mutations in BRCA1 or BRCA2; of these probands, 7 (0.8%) carried another pathogenic mutation in BRCA1 or BRCA2, and 31 (3.4%) carried a pathogenic mutation in another breast cancer gene (29 in CHEK2, and 1 each in BRIP1 and NBN). Of all inherited predispositions to breast cancer in the NYBCS, 73.8% (104 of 142) were due to a BRCA1 or BRCA2 founder allele, 4.9% (7 of 142) to another BRCA1 or BRCA2 mutation, and 21.8% (31 of 142) to a mutation in another gene. Overall, 14.1% (142 of 1007) of Ashkenazi Jewish patients with breast cancer in the NYBCS carried a germline mutation responsible for their disease: 11.0% (111 of 1007) in BRCA1 or BRCA2, and 3.1% (31 of 1007) in CHEK2 or another breast cancer gene. Of the 111 patients with BRCA1 or BRCA2 mutations, 57 (51.4%) had a mother or sister with breast or ovarian cancer and 54 patients (48.6%) did not.Conclusions and relevanceComprehensive sequencing would provide complete relevant genetic information for Ashkenazi Jewish patients with breast cancer.

Dataset Information

Evaluation of pathogenetic mutations in breast cancer predisposition genes in population-based studies conducted among Chinese women.

Publications

Evaluation of pathogenetic mutations in breast cancer predisposition genes in population-based studies conducted among Chinese women.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets