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

Zhang, Yunuo; Wu, Heming; Yu, Zhikang; Li, Liang; Zhang, Jinhong; Liang, Xinhong; Huang, Qingyan

doi:10.1186/s12885-022-09943-0

Cited by 8 publications

(7 citation statements)

References 85 publications

(89 reference statements)

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“…The BRCA gene mutation sites are associated with different populations. In the Chinese Hakka population, the most frequent mutation in the BRCA1 gene was c.2635G > T (p.Glu879*), with a frequency of 4/32 (12.5%), which is consistent with previous reports [ 28 ]. This variation involves a single nucleotide alteration in exon 10 of BRCA1 , resulting in an early translation stop signal that leads to nonfunctional protein products.…”

Section: Discussionsupporting

confidence: 90%

BRCA1 and BRCA2 germline mutations in Chinese Hakka breast cancer patients

Zhang,

Wu,

Gan

et al. 2024

BMC Med Genomics

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Objective To investigate the prevalence of BRCA1/2 gene variants and evaluate the clinical and pathological characteristics associated with these variants in Chinese Hakka breast cancer patients. Methods A total of 409 breast cancer patients were analyzed based on next-generation sequencing results, with 337 categorized as non-carriers and 72 as carriers of BRCA1/2 variants. Data on the patients’ BRCA1/2 gene mutation status, clinical and pathological characteristics, as well as menstrual and reproductive information, were collected, analyzed, compared, and tabulated. Logistic regression analysis was performed to explore the relationship between clinical characteristics and pathogenic variants. Results Among the patients, 72 were identified as carriers of pathogenic or likely pathogenic variants in BRCA1/2, while 337 had likely benign or benign mutations. The BRCA1 c.2635G > T (p. Glu879*) variant was detected at a high frequency, accounting for 12.5% (4/32) of the BRCA1 mutations, while the c.5164_5165del (p.Ser1722Tyrfs*4) variant was common among the BRCA2 mutations, accounting for 17.5% (7/40). It was observed that a higher proportion of BRCA1 carriers had the triple-negative breast cancer subtype, whereas more BRCA2 carriers exhibited estrogen receptor (ER) + and progesterone receptor (PR) + subtypes. Multivariate logistic regression analysis revealed that a family history of cancer (OR = 2.36, 95% CI = 1.00–5.54), bilateral cancer (OR = 4.78, 95% CI 1.61–14.20), human epidermal growth factor receptor 2 (HER2)- (OR = 8.23, 95% CI 3.25–20.84), and Ki67 ≥ 15% (OR = 3.88, 95% CI 1.41–10.65) were associated with BRCA1/2 mutations, with the age at diagnosis, age at menarche, and premenopausal status serving as covariates. Conclusions The most common pathogenic variant of the BRCA1 and BRCA2 in breast cancer patients was c.2635G > T and c.5164_5165del, respectively. Additionally, a family history of cancer, bilateral cancer, HER2-, and Ki67 ≥ 15% were identified as independent predictors of BRCA1/2 pathogenic variants.

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Section: Discussionsupporting

confidence: 90%

BRCA1 and BRCA2 germline mutations in Chinese Hakka breast cancer patients

Zhang,

Wu,

Gan

et al. 2024

BMC Med Genomics

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“…Zhang et al found that the prevalence and spectrum of variants in BRCA1/2 genes in the population which this study was conducted were different from those of other nationalities. 33 BRCA1 and BRCA2 are the tumor suppressor genes, and highly penetrating mutations in these genes result in a loss of tumor suppressor function and thus an increased risk of ovarian cancer. 34 Understanding whether the unique clinical and pathological features of ovarian cancer are associated with the BRCA1/2 gene mutation is essential to mitigate prognosis differences in the female population.…”

Section: Discussionmentioning

confidence: 99%

Association Between Germline BRCA1/2 Gene Variants and Clinicopathological Features of Ovarian Cancer

Luo,

Pan,

Rao

et al. 2024

IJGM

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Objective To investigate the relationship between BRCA1/2 gene mutation and clinicopathological features in ovarian cancer patients, so as to develop precise individualized treatment plan for patients. Methods Patients diagnosed with ovarian cancer between January 2018 and July 2023 who underwent BRCA1/2 genetic testing were retrospectively analyzed. The clinicopathological characteristics (age, body mass index (BMI), family history of ovarian cancer, pregnancy history, menopause status, tumor size, histopathology, Federation of Gynecology and Obstetrics (FIGO) staging, and ascites) of non-carriers and BRCA1/2 variant carriers were compared. Logistic regression analysis was used to explore the relationship between BRCA1/2 variants and clinicopathological characteristics of ovarian cancer. Results A total of 284 ovarian cancer patients were collected, and the subjects were divided into two groups, 197 non-carriers and 87 BRCA1/2 variants carriers. The proportion of serous ovarian carcinoma in BRCA1/2 variant carriers is higher than that in non- BRCA variant carriers (78.2% vs 60.9%, p =0.015). There were 51 patients with BRCA pathogenic or likely pathogenic variant, 22 patients with BRCA likely benign variant, and 14 patients with BRCA variants of uncertain significance (VUS). The proportion of serous ovarian carcinoma in patients with BRCA pathogenic/likely pathogenic variant is higher than that in patients with BRCA likely benign variant and BRCA VUS (94.1% vs 50.0% and 64.3%. p <0.001). There were no statistically significant differences in BMI, family history of ovarian cancer, pregnancy history, menopause status, maximum diameter of the tumor lesion, FIGO stage, and ascites among patients with different grades of variants. Multivariate logistic regression analysis showed that serous ovarian carcinoma was related to BRCA mutation (Serous carcinoma vs non-serous carcinoma: OR 2.145, 95% CI: 1.044–4.407) ( p =0.038). Conclusion Patients with BRCA1 variant develop ovarian cancer at a younger age than those with the BRCA2 variant. The proportion of FIGO stage III–IV in patients with BRCA pathogenic + likely pathogenic variant was significantly higher than those in patients with other variants. Germline BRCA1/2 variants were most frequently identified in serous ovarian carcinoma patients.

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“…To the best of our knowledge, the mutation hotspot in BRCA2 (I770) discovered in our study is the first reported among Chinese patients with gynecological cancer ( 48 – 50 ). Patients with BRCA2 mutations have a better prognosis than those with BRCA1 mutations ( 51 ).…”

Section: Discussionmentioning

confidence: 99%

“…reported among Chinese patients with gynecological cancer (48)(49)(50). Patients with BRCA2 mutations have better prognosis than those with BRCA1 mutations (51).…”

Section: B Amentioning

confidence: 98%

Clinical characterization and genomic landscape of gynecological cancers among patients attending a Chinese hospital

Jiang

Liu

et al. 2023

Front. Oncol.

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BackgroundGynecological cancers are the most lethal malignancies among females, most of which are associated with gene mutations. Few studies have compared the differences in the genomic landscape among various types of gynecological cancers. In this study, we evaluated the diversity of mutations in different gynecological cancers.MethodsA total of 184 patients with gynecological cancer, including ovarian, cervical, fallopian tube, and endometrial cancer, were included. Next-generation sequencing was performed to detect the mutations and tumor mutational burden (TMB). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were also conducted.ResultsWe found that 94.57% of patients had at least one mutation, among which single nucleotide variants, insertions and InDels were in the majority. TP53, PIK3CA, PTEN, KRAS, BRCA1, BRCA2, ARID1A, KMT2C, FGFR2, and FGFR3 were the top 10 most frequently mutated genes. Patients with ovarian cancer tended to have higher frequencies of BRCA1 and BRCA2 mutations, and the frequency of germline BRCA1 mutations (18/24, 75.00%) was higher than that of BRCA2 (11/19, 57.89%). A new mutation hotspot in BRCA2 (I770) was firstly discovered among Chinese patients with gynecological cancer. Patients with TP53, PIK3CA, PTEN, and FGFR3 mutations had significantly higher TMB values than those with wild-type genes. A significant cross was discovered between the enriched KEGG pathways of gynecological and breast cancers. GO enrichment revealed that the mutated genes were crucial for the cell cycle, neuronal apoptosis, and DNA repair.ConclusionVarious gynecological cancer types share similarities and differences both in clinical characterization and genomic mutations. Taken together with the results of TMB and enriched pathways, this study provided useful information on the molecular mechanism underlying gynecological cancers and the development of targeted drugs and precision medicine.

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

Cited by 8 publications

References 85 publications

BRCA1 and BRCA2 germline mutations in Chinese Hakka breast cancer patients

BRCA1 and BRCA2 germline mutations in Chinese Hakka breast cancer patients

Association Between Germline BRCA1/2 Gene Variants and Clinicopathological Features of Ovarian Cancer

Clinical characterization and genomic landscape of gynecological cancers among patients attending a Chinese hospital

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