Differences in Ovarian and Other Cancers Risks by Population and BRCA Mutation Location

Sekiguchi, Masayuki; Nishino, Kazumi; Enomoto, Takayuki

doi:10.3390/genes12071050

Cited by 27 publications

(28 citation statements)

References 89 publications

(120 reference statements)

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“…Regarding the difference in OC risk depending on the BRCA mutation location, BRCA1 and BRCA2 have the ovarian cancer cluster region (OCCR) in or near exon 11 and the breast cancer cluster region (BCCR) in multiple regions other than exon 11 so far [ 9 10 11 ]. However, there are few reports on the correlation between BRCA mutation location and age at diagnosis of OC.…”

Section: Introductionmentioning

confidence: 99%

Differences in age at diagnosis of ovarian cancer for each BRCA mutation type in Japan: optimal timing to carry out risk-reducing salpingo-oophorectomy

et al. 2022

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Objective BRCA1 and BRCA2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) by age 40 and 45, respectively. However, the carriers have a different way of thinking about their life plan. We aimed to investigate the distribution of age at diagnosis of ovarian cancer (OC) patients to examine the optimal timing of RRSO in the carriers. Methods We examined a correlation between age at diagnosis of OC and common mutation types in 3,517 probands that received BRCA genetic testing. Among them, germline BRCA1 mutation (g BRCA1 m), germline BRCA2 mutation (g BRCA2 m) and germline BRCA wild-type (g BRCA wt) were found in 185, 42 and 241 OC patients, respectively. Results The average age at diagnosis of OC in g BRCA1 m and g BRCA2 m was 51.3 and 58.3 years, respectively, and the difference from g BRCA wt (53.8 years) was significant. The g BRCA2 m carriers did not develop OC under the age of 40. The average age was 50.1 years for L63X and 52.8 years for Q934X in BRCA1 , and 55.1 years for R2318X and 61.1 years for STOP1861 in BRCA2 . The age at diagnosis in L63X or R2318X carriers was relatively younger than other BRCA1 or BRCA2 carriers, however their differences were not significant. With L63X and R2318X carriers, 89.4% (42/47) and 100% (7/7) of women were able to prevent the development of OC, respectively, when RRSO was performed at age 40. Conclusion There appears to be no difference in the age at diagnosis of OC depending on the type of BRCA common mutation. Further analysis would be needed.

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Section: Introductionmentioning

confidence: 99%

Differences in age at diagnosis of ovarian cancer for each BRCA mutation type in Japan: optimal timing to carry out risk-reducing salpingo-oophorectomy

et al. 2022

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“…The frequency of histological subtypes is known to be different between Japan and Western countries; the rate of clear cell carcinoma is higher in Japan (approximately 25%) than in the United States (approximately 6%), a four-fold difference [ 19 , 20 ]. The prevalence of g BRCA1/2 -PV in HGSC and clear cell carcinoma in OC is also reported as higher and lower, respectively, in Japan than in Western countries [ 21 , 22 ]. Therefore, the total prevalence of g BRCA1/2 -PV in all OC cases may be similar between Japan and Western countries despite the difference in the frequency of histologic subtypes.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Pathogenic Germline BRCA1/2 Variants and Their Association with Clinical Characteristics in Patients with Epithelial Ovarian Cancer in a Rural Area of Japan

Abe

Imoto

Tange

et al. 2022

Genes

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The prevalence of germline BRCA1 or BRCA2 pathogenic variants (gBRCA1/2-PV) in patients with primary epithelial ovarian cancer (OC) in a rural area of Japan and their association with clinical characteristics, including treatment response and survival outcome, were investigated. A total of 123 unbiased patients with OC were tested for gBRCA1 and gBRCA2 using next-generation sequencing-based targeted amplicon sequencing. Clinical characteristics of OC patients with and without gBRCA1/2 status were compared. The overall prevalence of gBRCA1/2-PV was 15.4% (19 cases), with gBRCA2-PV (10.5%, 13 cases) being more common than gBRCA1-PV (4.9%, 6 cases). Among the observed gBRCA1/2-PV, several novel variants were included, suggesting that gBRCA1/2-PV unique to the local area exist. gBRCA1/2-PV was significantly more prevalent in OC patients at an older age, with high-grade serous carcinoma, with advanced-stage tumors, and with a family history of breast cancer or hereditary breast and ovarian cancer syndrome (HBOC)-associated cancers. Patients with advanced-stage OC with gBRCA1/2-PV showed a significantly lower recurrence rate and tended to have better progression-free and overall survival than those with wild-type gBRCA1/2. Genetic testing for gBRCA1/2 status in all OC patients is useful not only for diagnosing HBOC in patients and their relatives to assess the risk of HBOC-associated cancers, but also to estimate therapy response and outcomes in patients.

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“…A variety of factors have been associated with its incidence, several of which are genetic. Indeed, approximately 40% of inherited cancers are due to mutations in the breast cancer susceptibility genes 1 and 2 ( BRCA1 and BRCA2 ) [ 2 ]. Recent estimates have shown that approximately 70% of patients with mutations in BRCA1 and 45% in BRCA2 will develop BC by the age of 70 [ 1 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

PARP-1 Expression and BRCA1 Mutations in Breast Cancer Patients’ CTCs

Sklias

Vardas

Pantazaka

et al. 2022

Cancers

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BRCA1 and PARP are involved in DNA damage repair pathways. BRCA1 mutations have been linked to higher likelihood of triple negative breast cancer (TNBC). The aim of the study was to determine PARP-1 expression and BRCA1 mutations in circulating tumor cells (CTCs) of BC patients. Fifty patients were enrolled: 23 luminal and 27 TNBC. PARP expression in CTCs was identified by immunofluorescence. Genotyping was performed by PCR-Sanger sequencing in the same samples. PARP-1 expression was higher in luminal (61%) and early BC (54%), compared to TNBC (41%) and metastatic (33%) patients. In addition, PARP-1 distribution was mostly cytoplasmic in luminal patients (p = 0.024), whereas it was mostly nuclear in TNBC patients. In cytokeratin (CK)-positive patients, those with the CK+PARP+ phenotype had longer overall survival (OS, log-rank p = 0.046). Overall, nine mutations were detected; M1 and M2 were completely new and M4, M7 and M8 were characterized as pathogenic. M7 and M8 were predominantly found in metastatic TNBC patients (p = 0.014 and p = 0.002). Thus, PARP-1 expression and increased mutagenic burden in TNBC patients’ CTCs, could be used as an indicator to stratify patients regarding therapeutic approaches.

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Differences in Ovarian and Other Cancers Risks by Population and BRCA Mutation Location

Cited by 27 publications

References 89 publications

Differences in age at diagnosis of ovarian cancer for each BRCA mutation type in Japan: optimal timing to carry out risk-reducing salpingo-oophorectomy

Differences in age at diagnosis of ovarian cancer for each BRCA mutation type in Japan: optimal timing to carry out risk-reducing salpingo-oophorectomy

Prevalence of Pathogenic Germline BRCA1/2 Variants and Their Association with Clinical Characteristics in Patients with Epithelial Ovarian Cancer in a Rural Area of Japan

PARP-1 Expression and BRCA1 Mutations in Breast Cancer Patients’ CTCs

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