Prevalence and spectrum of <i>BRCA</i> germline variants in mainland Chinese familial breast and ovarian cancer patients

Kim, Yeong C.; Zhao, Lei; Zhang, Hanwen; Huang, Ye; Cui, Jian; Xiao, Fengxia; Downs, Bradley M.; Wang, San Ming

doi:10.18632/oncotarget.7144

Cited by 54 publications

(67 citation statements)

References 27 publications

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“…Although the majority of the pathogenic mutations were previously reported, 32 novel mutations were identified in our study, which were not described in the literature nor recorded in public databases, such as BIC, ClinVar or LOVD. Two novel pathogenic mutations in BRCA1 : c.283_286delCTTG and c.4573C > T, were both identified in two unrelated EOC patients (Table ).…”

Section: Resultsmentioning

confidence: 88%

BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic‐related mutations in BRCA1 associated with an increased risk of ovarian cancer

Shi

Wang

Xie

et al. 2017

Intl Journal of Cancer

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NC 6 Plateforme de g enomique des cancers, Centre L eon B erard, Laboratoire de la g en etique constitutionnelle HCL-CLB, Lyon, France BRCA1/2 are cancer predisposition genes involved in hereditary breast and ovarian cancer (HBOC). Mutation carriers display an increased sensitivity to inhibitors of poly(ADP-ribose) polymerase (PARP). Despite a number of small-size hospital-based studies being previously reported, there is not yet, to our knowledge, precise data of BRCA1/2 mutations among Chinese ovarian cancer patients. We performed a multicenter cohort study including 916 unselected consecutive epithelial ovarian cancer (EOC) patients from eastern China to screen for BRCA1/2 mutations using the next-generation sequencing approach. A total of 153 EOC patients were found to carry pathogenic germline mutations in BRCA1/2, accounting for an overall mutation incidence of 16.7% with the predominance in BRCA1 (13.1%) compared with BRCA2 (3.9%). We identified 53 novel pathogenic mutations, among which the c.283_286delCTTG and the c.4573C > T of BRCA1 were both found in two unrelated patients. More importantly, the most common mutation found in this study, c.5470_5477del8 was most likely to be Chinese populationrelated without an apparent founder origin. This hot-spot mutation was presumably associated with an increased risk of ovarian cancer. Taken together, germline BRCA1/2 mutations were common in Chinese EOC patients with distinct mutational spectrum compared to Western populations. Our study contributes to the current understanding of BRCA1/2 mutation prevalence worldwide. We recommend BRCA1/2 genetic testing to all Chinese women diagnosed with EOC to identify HBOC families, to provide genetic counseling and clinical management for at-risk relatives. Mutation carriers may also benefit from PARP-targeted therapies.Ovarian cancer is the third most commonly diagnosed cancer and the first leading cause of deaths among gynecologic malignancies worldwide.

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Section: Resultsmentioning

confidence: 88%

BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic‐related mutations in BRCA1 associated with an increased risk of ovarian cancer

Shi

Wang

Xie

et al. 2017

Intl Journal of Cancer

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“…Due largely to the scientific and economic advantages, current knowledge of genetic predisposition are largely derived from the developed countries of European and North American populations. Increased data from recent studies in Latino, Africa, and Asia populations demonstrate that genetic predisposition for familial breast cancer can be ethnic-specific in reflecting human evolution and geographic differences [4–10]. Without the information from different ethnic populations, our understanding of genetic predisposition for familial breast cancer will remain incomplete; and relying on the existing information as the solely references is not adequate to identify the patients from other ethnicities.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic predispositions for approximately half of familial breast cancers have been determined, and studies are actively going on to determine the unknown genetic predispositions for the remaining cases [1–3]. Recent studies demonstrate that genetic predispositions for familial breast cancer can be ethnic-specific, as well exemplified by the different spectrum of germline mutation in BRCA1 and BRCA2 between different ethnic populations [4–10]. Knowledge of ethnic-specific genetic predispositions for familial breast cancer is important, as it directly affects the accuracy of clinical diagnosis and intervention in patients of different ethnicities.…”

Section: Introductionmentioning

confidence: 99%

Unique Features of Germline Variation in Five Egyptian Familial Breast Cancer Families Revealed by Exome Sequencing

et al. 2017

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Genetic predisposition increases the risk of familial breast cancer. Recent studies indicate that genetic predisposition for familial breast cancer can be ethnic-specific. However, current knowledge of genetic predisposition for the disease is predominantly derived from Western populations. Using this existing information as the sole reference to judge the predisposition in non-Western populations is not adequate and can potentially lead to misdiagnosis. Efforts are required to collect genetic predisposition from non-Western populations. The Egyptian population has high genetic variations in reflecting its divergent ethnic origins, and incident rate of familial breast cancer in Egypt is also higher than the rate in many other populations. Using whole exome sequencing, we investigated genetic predisposition in five Egyptian familial breast cancer families. No pathogenic variants in BRCA1, BRCA2 and other classical breast cancer-predisposition genes were present in these five families. Comparison of the genetic variants with those in Caucasian familial breast cancer showed that variants in the Egyptian families were more variable and heterogeneous than the variants in Caucasian families. Multiple damaging variants in genes of different functional categories were identified either in a single family or shared between families. Our study demonstrates that genetic predisposition in Egyptian breast cancer families may differ from those in other disease populations, and supports a comprehensive screening of local disease families to determine the genetic predisposition in Egyptian familial breast cancer.

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“…However, a lack of basic information about the prevalence and spectrum of BRCA mutations hinders research progress on the etiology (6) and risk evaluation of model of breast cancer prevention in China. Additionally, because of the large presence of ethnic-specific contexts (11)(12)(13)(14), the Western risk evaluation models do not apply well to China. Therefore, the following paper assembled a wide-range clinic-based cross-sectional study of hereditary risk among BC patients, who were representative for BRCA mutations study.…”

Section: Introductionmentioning

confidence: 99%

Multicenter cross‑sectional screening of the BRCA gene for Chinese high hereditary risk breast cancer populations

et al. 2018

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Abstract. Due to lack of systematic reviews, BRCA, DNA Repair Associated (BRCA) mutations in the Chinese population are not completely understood. The following study investigates the prevalence and type of BRCA mutations in Chinese patients with high hereditary risk of breast cancer (BC).Patients Drwere recruited from 14 cities between October 2015 and February 2016, and were selected based on family and personal medical history. BRCA mutations were analyzed by collecting blood samples from all participants. 437 BC patients were included. A total of seventy-six (17.4%) mutation carriers were identified with no geographic difference. The mutation rate in the early-onset BC patients was lower compared to family history of breast/ovarian cancer (OC), bilateral BC, male BC, BC&OC or meeting ≥2 criteria (9.2 vs. 21.7, 24.0, 22.2, 16.7 and 24.3%, respectively, P=0.007). A total of 61 mutation sites were identified (BRCA1 32, BRCA2 29) including 47.5% novel sites and extra 10 variants of uncertain significance. A total of five sites were repeated in more than one unrelated patient. A total of 11 sites were associated with hereditary breast and ovarian cancer syndrome, two of which were confirmed by family pedigrees. Compared with BRCA -patients, patients with BRCA1 mutation tended to be triple-negative BC (P<0.001), whereas patients with BRCA2 mutation were more likely to be hormone receptor positive

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Prevalence and spectrum of BRCA germline variants in mainland Chinese familial breast and ovarian cancer patients

Abstract: ABSTRACT

Cited by 54 publications

References 27 publications

BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic‐related mutations in BRCA1 associated with an increased risk of ovarian cancer

BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic‐related mutations in BRCA1 associated with an increased risk of ovarian cancer

Unique Features of Germline Variation in Five Egyptian Familial Breast Cancer Families Revealed by Exome Sequencing

Multicenter cross‑sectional screening of the BRCA gene for Chinese high hereditary risk breast cancer populations

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