Mutational analysis of BRCA1 and BRCA2 genes in Chinese ovarian cancer identifies 6 novel germline mutations

Khoo, Ui‐Soon; Ngan, Hextan Ys; Cheung, Annie Nga‐Yin; Chan, Kelvin Yuen-Kwong; Lu, Junyan; Chan, Vivian; Lau, Susan; Andrulis, Irene L.; Özçelik, Hilmi

doi:10.1002/1098-1004(200007)16:1<88::aid-humu16>3.0.co;2-g

Cited by 38 publications

(33 citation statements)

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“…These include 1529del4; reported in British and United States women (21), 6633del5, which was observed previously in Austrian, Japanese, and Italian women (26 -29,) and is also noted in the Breast Cancer Information Core, an international and voluntary, web-based databank of BRCA1 and BRCA2 mutations reported by Ͼ20 participating groups (30). 6 Although not highly quantitative, the Breast Cancer Information Core provides a valuable resource for tracking the occurrence of mutations throughout both the BRCA1 and BRCA2 genes. Also observed was a 5301insA change in BRCA2, reported several times in European women (29,31,32) and in women of Near and Middle Eastern descent in the Breast Cancer Information Core.…”

Section: Discussionmentioning

confidence: 69%

“…An analysis of 60 ovarian cases from Hong Kong, unselected for family history, revealed that 11.3% and 2.1%, carried germ-line mutations in BRCA1 and BRCA2, respectively (6). A subsequent analysis of 214 consecutive ovarian cases, also from Hong Kong, suggested a founder effect associated with the 1081delG BRCA1 mutation in women of Southern Chinese descent (7).…”

Section: Introductionmentioning

confidence: 99%

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BRCA1 and BRCA2 Mutations in Women from Shanghai China

Suter¹,

Ray

et al. 2004

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Little is known about the frequency of germ-line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 among Asian populations. We investigated the distribution of BRCA1 and BRCA2 germline mutations and polymorphisms in a cohort of women from Shanghai, China.Study subjects totaled 1306, and included 645 women with breast cancer, 342 women with benign breast disease, and 319 unaffected controls, born between 1924 and 1958, selected from women enrolled in a randomized trial of Breast Self-Examination in Shanghai, China. Women were selected without regard to family history of breast or ovarian cancer. All of the coding regions and exon-intron boundaries were screened. Data were analyzed with respect to age at diagnosis, and family history of breast and ovarian cancer.The prevalence of known disease-associated mutations in women with breast cancer was 1.1% each, for BRCA1 and BRCA2. Among breast cancer cases with a family history of breast or ovarian cancer, 8.1% and 2.7% carried likely BRCA1 and BRCA2 disease-associated mutations, respectively.Overall, these results suggest that inherited susceptibility to breast cancer due to germ-line BRCA1/2 mutations among women with a family history of breast cancer is comparable between women from Shanghai and Caucasian women of Western European descent. Most alterations observed appear unique to the Chinese population, suggesting a resource that will be useful for assessing risk among both Chinese women and United States women of Chinese descent. IntroductionAlthough the incidence of breast cancer in China is about one-third that in the United States (1), the overall rate of breast cancer in women from China has been increasing (2). Little is known regarding the role of inherited susceptibility genes in breast cancer risk among Chinese women. To develop genetic screening guidelines for both Chinese women and United States women of Chinese descent, a population-based assessment of BRCA1 and BRCA2 germ-line mutation distribution and frequency is needed.To date, information regarding the frequency of BRCA1 and BRCA2 mutations in Chinese women with breast cancer has been derived from two small hospital-based reports. In the first, 76 consecutive breast cancer cases diagnosed before age 40, and 16 women with a family history of breast or ovarian cancer, were screened for germ-line mutations in BRCA1 (3). Protein truncating mutations were observed in 8.6% of women. In the second study, 3.8% of 130 tumors collected from mastectomy patients in Hong Kong were found to carry protein-truncating mutations in BRCA1 (4). The prevalence was 8.0% in patients diagnosed under age 45 (4). In the same study, investigators observed a single variant, 589delCT, in three unrelated patients from within a single province of Southern China, suggesting a possible founder effect. However a later more detailed study of 60 early onset breast cancer cases did not reveal any additional carriers (4, 5). Neither study examined the role of BRCA2 mutations in Chinese women.Studies of women...

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Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

BRCA1 and BRCA2 Mutations in Women from Shanghai China

Suter¹,

Ray

et al. 2004

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Haplotype analysis of the patients with recurrent mutation showed that only in the two cases with 1081delG in BRCA1, shared haplotype was seen for all four markers detected. The mutations were identified in DNA extracted from representative tissue blocks and were confirmed to harbor in the germline on further PCR and DNA sequencing of non-tumor tissue [45,46].…”

Section: Discussionmentioning

confidence: 99%

The prevalence of BRCA1 and BRCA2 germline mutations in high-risk breast cancer patients of Chinese Han nationality: two recurrent mutations were identified

Rao

et al. 2007

Breast Cancer Res Treat

111

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To have an overview of the role of BRCA1 and BRCA2 genes among Chinese high-risk breast cancer patients, we analyzed 489 such high-risk breast cancer patients from four breast disease clinical centers in China, by using PCR-DHPLC or SSCP-DNA sequencing analysis. Allelotype analysis was done at five short tandem repeat (STR) markers in or adjacent to BRCA1 on the recurrent mutation carriers. For those analyzed both genes, 8.7% of early-onset breast cancer cases and 12.9% of familial breast cancer cases had a BRCA1 or BRCA2 mutation, as compared with the 26.1% of cases with both early-onset breast cancer and affected relatives. For those reporting malignancy family history other than breast/ovarian cancer, the prevalence of BRCA1/2 mutation is about 20.5%, and it was significantly higher than the patients only with family history of breast/ovarian cancer (P = 0.02). The family history of ovarian cancer (26.7% vs. 11.9%) and stomach cancer (23.8% vs. 11.8%) doubled the incidence of BRCA1/2, but the difference did not reach the statistical significance. Two recurrent mutations in BRCA1, 1100delAT and 5589del8, were identified. The recurrent mutations account for 34.8% BRCA1 mutations in our series. Similar allelotypes were detected in most STR status for those harboring the same mutations. The BRCA1 associated tumors were more likely to exhibit a high tumor grade, negative C-erbB-2/neu status and triple negative (ER, PgR and C-erbB-2/neu negative) status (P < 0.05). We recommended the BRCA1 and BRCA2 genetic analysis could be done for high-risk breast cancer patient in Chinese population, especially for those with both early-onset breast cancer and affected relatives. There may be some degree of shared ancestry for the two recurrent BRCA1 mutations in Chinese.

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“…The lifetime risk of developing ovarian cancer in BRCA1 and BRCA2 carriers is 28-44% [1,2,6,7]. Estimates of the frequency of BRCA1 and BRCA2 germline mutations in ovarian cancer patients have ranged between 2-12% and 2-6% for BRCA1 and BRCA2 mutations, respectively [2,3,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Improved survival in BRCA2 carriers with ovarian cancer

et al. 2006

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Objectives-The objective of this study was to investigate survival of ovarian cancer patients with BRCA1 and BRCA2 mutations compared to those without mutations in a population-based sample of incident epithelial ovarian cancer cases. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript the two analyses were similar, thus data involving the 209 invasive epithelial cancer cases are presented, as this was judged to be more clinically relevant. NIH Public AccessResults-In the multivariate analysis, BRCA status and stage were statistically significant, and were adjusted for in the survival analysis model. The Kaplan-Meier method estimated expected survival at 4 years of 83% of BRCA2 carriers compared to 37% of BRCA1 carriers and 12% of non-carriers. There was a statistically significant difference between BRCA2 carriers and noncarriers (p = 0.013). No statistically significant survival differences were seen for BRCA1 carriers when compared with either BRCA2 carriers or non-carriers.Conclusion-These data suggest that BRCA2 mutation carriers with ovarian cancer may have better survival than BRCA1 carriers and non-carriers. The etiology of this possible survival advantage is currently unknown. Larger studies are needed to confirm these results and to clarify their etiology and clinical significance.

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Mutational analysis of BRCA1 and BRCA2 genes in Chinese ovarian cancer identifies 6 novel germline mutations

Cited by 38 publications

References 13 publications

BRCA1 and BRCA2 Mutations in Women from Shanghai China

BRCA1 and BRCA2 Mutations in Women from Shanghai China

The prevalence of BRCA1 and BRCA2 germline mutations in high-risk breast cancer patients of Chinese Han nationality: two recurrent mutations were identified

Improved survival in BRCA2 carriers with ovarian cancer

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