The First Nationwide Multicenter Prevalence Study of Germline BRCA1 and BRCA2 Mutations in Chinese Ovarian Cancer Patients

Wu, Xiaohua; Wu, Lingying; Kong, Beihua; Liu, Jihong; Yin, Rong; Wen, Hao; Li, Ning; Bu, Hualei; Feng, Yanling; Li, Qingli; Lu, Xuesong; Wei, Jia; Zhu, Xuehua; Mills, John; Ellison, Gillian; Gutjahr, Thorsten S.; Liu, Yuzhen

doi:10.1097/igc.0000000000001065

Cited by 73 publications

(86 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This BRCA2 predominance was previously observed in prostate cancer patients 23 . However, the majority of gBRCAm in ovarian cancer are predominantly composed of BRCA1 mutations (172/235, 73.2%) 2 . In prostate cancer, patients with germline BRCA2 mutations showed elevated global genomic instability and harbored unique mutations that were rarely or not yet been reported in sporadic localized prostate cancer 24,25 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prevalence and clinical significance of pathogenic germline BRCA1/2 mutations in Chinese non-small cell lung cancer patients

Yang

et al. 2019

Cancer Biol Med

View full text Add to dashboard Cite

Objective: Germline alterations in the breast cancer susceptibility genes type 1 and 2, BRCA1 and BRCA2, predispose individuals to hereditary cancers, including breast, ovarian, prostate, pancreatic, and stomach cancers. Accumulating evidence suggests inherited genetic susceptibility to lung cancer. The present study aimed to survey the prevalence of pathogenic germline BRCA mutations (gBRCAm) and explore the potential association between gBRCAm and disease onset in Chinese advanced non-small cell lung cancer (NSCLC) patients. Methods: A total of 6,220 NSCLC patients were screened using capture-based ultra-deep targeted sequencing to identify patients harboring germline BRCA1/2 mutations. Results: Out of the 6,220 patients screened, 1.03% (64/6,220) of the patients harbored the pathogenic gBRCAm, with BRCA2 mutations being the most predominant mutations (49/64, 76.5%). Patients who developed NSCLC before 50 years of age were more likely to carry gBRCAm (P = 0.036). Among the patients harboring classic lung cancer driver mutations, those with concurrent gBRCAm were significantly younger than those harboring the wild-type gBRCA (P = 0.029). By contrast, the age of patients with or without concurrent gBRCAm was comparable to those of patients without the driver mutations (P = 0.972). In addition, we identified EGFR-mutant patients with concurrent gBRCAm who showed comparable progression-free survival but significantly longer overall survival (P = 0.002) compared to EGFR-mutant patients with wild-type germline BRCA. Conclusions: Overall, our study is the largest survey of the prevalence of pathogenic gBRCAm in advanced Chinese NSCLC patients. Results suggested a lack of association between germline BRCA status and treatment outcome of EGFR-TKI. In addition, results showed a positive correlation between pathogenic gBRCAm and an early onset of NSCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Approximately, 5% of breast cancer cases and 20%–30% of ovarian cancers are caused by germline alterations in the breast cancer susceptibility type 1 and 2 ( BRCA1 and BRCA2 ) genes 1,2 . Women with germline BRCA mutation ( gBRCAm ) have significantly higher lifetime risk of developing breast, ovarian, tubal, and peritoneal cancers.…”

Section: Introductionmentioning

confidence: 99%

Prevalence and clinical significance of pathogenic germline BRCA1/2 mutations in Chinese non-small cell lung cancer patients

Yang

et al. 2019

Cancer Biol Med

View full text Add to dashboard Cite

show abstract

“…Our analysis has shown that this frequency among Chinese OC patients was higher (21.8%) (Figure c). In fact, one large sample size screening (826 patients) indicated that this variant frequency in Chinese OC patients was 28.5% (Wu et al, ). Family history appeared to be a strong risk factor since BRCA1/2 pathogenic variant was found in 41.0% of patients with family history.…”

Section: Resultsmentioning

confidence: 99%

“…The prevalence of germline BRCA1/2 variants shows a large variation across different ethnicities, ranging from 6.5% to 25.0% in BC and from 12.1% to 29% in OC (Han et al, ; Kim et al, ; Robson et al, ; Weitzel et al, ). Due to remarkable advances in next‐generation sequencing (NGS) technologies (Rainville & Rana, ), it is now possible to investigate the prevalence of different BRCA1/2 variants in patients of distinct ethnicities, as well as their clinical significance (Sun et al, ; Wu et al, ). It is known that the homologous recombination repair function can be affected by pathogenic BRCA1/2 variants, which are randomly distributed along with coding and noncoding regions, with no defined hotspots (Weitzel et al, ).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients

et al. 2019

View full text Add to dashboard Cite

The identification and interpretation of germline BRCA1/2 variants become increasingly important in breast and ovarian cancer (OC) treatment. However, there is no comprehensive analysis of the germline BRCA1/2 variants in a Chinese population. Here we performed a systematic review and meta-analysis on such variants from 94 publications. A total of 2,128 BRCA1/2 variant records were extracted, including 601 from BRCA1 and 632 from BRCA2. In addition, 414, 734, 449, and 307 variants were also recorded in the BIC, ClinVar, ENIGMA, and UMD databases, respectively, and 579 variants were newly reported. Subsequent analysis showed that the overall germline BRCA1/2 pathogenic variant frequency was 5.7% and 21.8% in Chinese breast and OC, respectively. Populations with high-risk factors exhibited a higher pathogenic variant percentage. Furthermore, the variant profile in Chinese is distinct from that in other ethnic groups with no distinct founder pathogenic variants. We also tested our in-house American College of Medical Genetics-guided pathogenicity interpretation procedure for Chinese BRCA1/2 variants. Our results achieved a consistency of 91.2-97.6% (5-grade classification) or 98.4-100% (2-grade classification) with public databases. In conclusion, this study represents the first comprehensive meta-analysis of Chinese BRCA1/2 variants and validates our in-house pathogenicity interpretation procedure, thereby providing guidance for further PARP inhibitor development and companion diagnostics in the Chinese population.

show abstract

“…In a study of 916 patients with Chinese epithelial ovarian cancer, the incidence of BRCA1/2 mutation was 16.7%, with a BRCA1 mutation rate of 13.1%, BRCA2 mutation rate of 3.9% and concurrent BRCA1 and BRCA2 mutation rate of 0.3% . In another nationwide multicenter study of 826 Chinese patients, the incidence of germline BRCA1/2 mutation was 28.5%, with a BRCA1 mutation rate of 20.8% and BRCA2 mutation rate of 7.6% . The strikingly different prevalences found in previous studies and the deficiency of clinical characteristics calls for further large population‐based studies on this issue.…”

Section: Introductionmentioning

confidence: 98%

BRCA mutation frequency and clinical features of ovarian cancer patients: A report from a Chinese study group

Chen

et al. 2019

J of Obstet and Gynaecol

Self Cite

View full text Add to dashboard Cite

Aim: Subjects with germline BRCA1/2 mutations ( gBRCAm) have an increased risk of developing breast cancer and ovarian cancer. At present, knowledge of BRCA1/2 mutation frequency in Chinese patients with ovarian cancer is still insufficient, and the detailed clinical information of these patients is poorly understood. Methods: A total of 547 unselected ovarian cancer patients were enrolled, and their gBRCAm status was detected. Clinical characteristics including age, personal and family history, histopathologic diagnosis, carbohydrate antigen 125 (CA-125) level, ascites, Federation International of Gynecology and Obstetrics (FIGO) stage, residual lesions, platinum sensitivity, recurrence interval and survival information were collected. Accurate assessments of disease response were based on the RECIST standard or CA-125 level. Results: In 547 patients with ovarian cancer, we detected 129 (23.6%) patients with pathogenic mutations, 84 patients with BRCA1 mutations (15.4%) and 45 patients with BRCA2 mutations (8.2%). Twenty-five novel mutations were identified, and the mutation of BRCA1, c.5470_5477del8, was the most common mutation in this study. BRCA1/2 mutations were significantly associated with age; personal and family history; FIGO stage; secondary recurrence interval; sensitivity to platinum in 1st, 2nd and 3rd line treatment; and response to doxorubicin liposomes. Patients with BRCA1/2 mutations showed significant advantages in 3-and 5-year survival rates but no advantage in long-term survival. Conclusion: BRCA1/2 mutation prevalence in Chinese ovarian cancer patients is higher than the international rate. We recommend BRCA1/2 testing for patients with family histories and personal histories of malignancy and genetic counseling for cancer in healthy people with high-risk family histories.

show abstract

The First Nationwide Multicenter Prevalence Study of Germline BRCA1 and BRCA2 Mutations in Chinese Ovarian Cancer Patients

Abstract: Germline BRCA1/2 mutations is common in Chinese ovarian cancer patients. This study implies that all ovarian patients should be tested for gBRCAm status regardless of family history and histopathology.

Cited by 73 publications

References 45 publications

Prevalence and clinical significance of pathogenic germline BRCA1/2 mutations in Chinese non-small cell lung cancer patients

Prevalence and clinical significance of pathogenic germline BRCA1/2 mutations in Chinese non-small cell lung cancer patients

Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients

BRCA mutation frequency and clinical features of ovarian cancer patients: A report from a Chinese study group

Contact Info

Product

Resources

About