Prevalence of<i>BRCA1/2</i>germline mutations in 21 401 families with breast and ovarian cancer

Kast, Karin; Rhiem, Kerstin; Wappenschmidt, Barbara; Hahnen, Eric; Hauke, Jan; Bluemcke, Britta; Zarghooni, V.; Herold, N; Ditsch, Nina; Kiechle, Marion; Braun, Michael; Fischer, Christine; Dikow, Nicola; Schott, Sarah; Rahner, Nils; Niederacher, Dieter; Fehm, Tanja; Gehrig, Andrea; Mueller-Reible, Clemens; Arnold, Norbert; Maass, Nicolaì; Borck, Guntram; Gregorio, Nikolaus de; Scholz, Caroline; Auber, Bernd; Varon-Manteeva, Raymonda; Speiser, Dorothee; Horváth, Judit; Lichey, Nadine; Wimberger, Pauline; Stark, Sylvia; Faust, Ulrike; Weber, Bernhard H. F.; Emons, Günter; Zachariae, Silke; Meindl, Alfons; Schmutzler, Rita K.; Engel, Christoph

doi:10.1136/jmedgenet-2015-103672

Cited by 195 publications

(156 citation statements)

References 33 publications

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…Most BRCA1 and BRCA2 pathogenic variants are predicted to produce a truncated protein product and thus loss of protein function [148]. However, the prevalence of BRCA1 and BRCA2 mutations is only approximately 24% [149, 150]. Recently, exome sequencing has uncovered substantial locus heterogeneity among affected families without BRCA1 or BRCA2 mutations [151, 152].…”

Section: Initial Results From Associations From Large-scale Sequencinmentioning

confidence: 99%

The impact of rare and low-frequency genetic variants in common disease

2017

View full text Add to dashboard Cite

Despite thousands of genetic loci identified to date, a large proportion of genetic variation predisposing to complex disease and traits remains unaccounted for. Advances in sequencing technology enable focused explorations on the contribution of low-frequency and rare variants to human traits. Here we review experimental approaches and current knowledge on the contribution of these genetic variants in complex disease and discuss challenges and opportunities for personalised medicine.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1212-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Initial Results From Associations From Large-scale Sequencinmentioning

confidence: 99%

The impact of rare and low-frequency genetic variants in common disease

2017

View full text Add to dashboard Cite

show abstract

“…At the same time, there existed distinct population‐dependent differences from country to country. The German Consortium for Hereditary Breast and Ovarian Cancer (GC‐HBOC) presented a comprehensive BRCA screening and revealed a higher mutation frequency in BRCA1 than that in BRCA2 . In contrast, studies in the United Kingdom demonstrated a similar or inferior prevalence of BRCA1 mutations compared with BRCA2 mutations .…”

Section: Discussionmentioning

confidence: 99%

The spectrum of BRCA mutations and characteristics of BRCA‐associated breast cancers in China: Screening of 2,991 patients and 1,043 controls by next‐generation sequencing

Lang

Shi

et al. 2017

Intl Journal of Cancer

117

View full text Add to dashboard Cite

To characterize the prevalence of BRCA mutations and characteristics of BRCA carriers in China and to update the clinical recommendations for BRCA testing, we conducted a wide screen for BRCA mutations using next-generation sequencing (NGS). A total of 4,034 Chinese subjects were screened for germline BRCA1/2 mutations, including 2,991 breast cancer patients and 1,043 healthy individuals from the community enrolled as controls. We developed an NGS-based approach to perform BRCA1/2 screening. BRCA mutations were identified in 9.1% (232/2,560) of cases with at least one risk factor, in 3.5% (15/431) of sporadic patients and in 0.38% (4/1,043) of healthy controls. The mutation frequency ranged from 8.9 to 15.2% in cohorts with a single risk factor to 16.6-100% in groups with multiple risk factors. We identified 70 novel BRCA mutations. A high frequency of BRCA1 c.5470_5477del was detected, accounting for 13.9% (16/115) of the BRCA1 mutations detected in our study. Clinical characteristics such as family history, invasive carcinoma, negative human epidermal growth factor receptor 2 (HER2), high Ki67 index, lymph node status, and high tumour grade were closely related to BRCA mutations. BRCA2 carriers had poorer disease-free survival among HER2- or hormone receptor-positive patients (hazard ratio = 1.892; 95% confidence interval: 1.132-3.161; p = 0.013). This study shows that BRCA mutation carriers could be frequently identified among breast cancer patients with multiple risk factors. Importantly, we established an NGS-based pipeline for BRCA1/2 testing in clinical practice and strongly suggest that breast cancer patients of premier- and moderate-grade risks receive BRCA1/2 mutations testing in China.

show abstract

“…Furthermore, the 10-year risk of developing ovarian cancer has been reported to be 12.7% and 6.8% for women carrying BRCA1 and BRCA2 mutations respectively [21]. A recent study of 21,401 families suspected of having a deleterious BRCA mutation showed that 24% of the families carried a pathogenic BRCA1 or BRCA2 mutation [22]. Because BRCA1 and BRCA2 are tumor suppressor genes, they are functionally recessive, and therefore, both copies of the allele must be mutated in the cell for breast cancer to develop (Figure 2).…”

Section: Role Of Brca In Tumorigenesismentioning

confidence: 99%

BRCA1 and BRCA2 mutations and treatment strategies for breast cancer

Godet¹,

Gilkes²

2017

Integr Cancer Sci Therap.

146

101

View full text Add to dashboard Cite

Breast cancer is a global burden with a woman's lifetime risk of developing breast cancer at 1 in 8. Although breast cancer is a disease that affects mostly women, the lifetime risk in men is about 1 in 1000. Most cases of breast cancer are associated with somatic mutations in breast cells that are acquired during a person's lifetime. In this scenario, the mutations are not inherited and they do not cluster in families. In hereditary breast cancer, the specific genetic factors involved will determine the inherited cancer risk. Inherited mutations in the BRCA1 or BRCA2 genes have been well-described, but mutations in ATM, CDH1, CHEK2, PALB2, PTEN, STK11, and TP53 also confer breast cancer risk. Understanding the functional significance of hereditary mutations has opened new paths for breast cancer prevention and is uncovering promising treatment strategies

show abstract

Prevalence ofBRCA1/2germline mutations in 21 401 families with breast and ovarian cancer

Abstract: Our data provide guidance for healthcare professionals and decision-makers to identify individuals who should undergo genetic testing for hereditary breast and ovarian cancer. Moreover, it supports informed decision-making of counselees on the uptake of genetic testing.

Cited by 195 publications

References 33 publications

The impact of rare and low-frequency genetic variants in common disease

The impact of rare and low-frequency genetic variants in common disease

The spectrum of BRCA mutations and characteristics of BRCA‐associated breast cancers in China: Screening of 2,991 patients and 1,043 controls by next‐generation sequencing

BRCA1 and BRCA2 mutations and treatment strategies for breast cancer

Contact Info

Product

Resources

About