Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer

Thirthagiri, Eswary; Lee, S Y; Kang, Peter Choon Eng; Lee, D S; Toh, Gaik Theng; Selamat, Suhaida A.; Yoon, Sy; Taib, Nur Aishah Mohd; Thong, Meow‐Keong; Yip, Cheng‐Har; Teo, Soo‐Hwang

doi:10.1186/bcr2118

Cited by 78 publications

(81 citation statements)

References 42 publications

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“…These observations suggest that 1014DelGT might be a common mutation in the Muslim community and might have migrated to the Indian population through a pool of Muslim immigrants (Liede et al, 2009). In North-Eastern region, the mutation of 3889DelAG is higher than the rest of the mutation found (Figure 1f), out of nine, three have the family history and found scattered in studied population; it also found in various populations of the world (Thirthagiri et al, 2008;Farooq et al, 2011). The location of 3889AG is towards the C terminus of BRCA1, within the transcriptional activation domain, a region as well reported to interact with the BRCA2 protein, which plays an important role in double stranded break (DSB) repair (Roy et al, 2012).…”

Section: Discussionmentioning

confidence: 69%

Screening of 185DelAG, 1014DelGT and 3889DelAG BRCA1 Mutations in Breast Cancer Patients from North-East India

Hansa

Kannan²,

Ghosh³

2012

Asian Pacific Journal of Cancer Prevention

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Around 1.35 million people of worldwide suffer from breast cancer each year, whereas in India, 1 in every 17 women develops the disease. Mutations of the Breast Cancer 1 (BRCA1) gene account for the majority of breast/ ovarian cancer families. The purpose of study was to provide a prevalence of BRCA1 germline mutations in the North-East Indian population. In relation to the personal and family history with the breast cancer, we found mutations in 6.25% and 12.5% respectively. Three mutations, 185DelAG, 1014DelGT and 3889DelAG, were observed in our North-East Indian patients in exons 2 and 11, resulting in truncation of the BRCA1 protein by forming stop codons individually at amino acid positions 39, 303 and 1265. Our results point to a necessity for an extensive mutation screening study of high risk breast cancer cases in our North-East Indian population, which will provide better decisive medical and surgical preventive options.

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Section: Discussionmentioning

confidence: 69%

Screening of 185DelAG, 1014DelGT and 3889DelAG BRCA1 Mutations in Breast Cancer Patients from North-East India

Hansa

Kannan²,

Ghosh³

2012

Asian Pacific Journal of Cancer Prevention

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“…Patients were recruited as part of a study into the genetic factors of breast cancer in Malaysia's multiethnic population, using previously described identification and recruitment schemes that were ethically approved. 24 England. Breast and ovarian cancer families have been tested for BRCA1/2 mutations since 1996 in the Manchester region of North-West England.…”

Section: Participant Identification and Recruitmentmentioning

confidence: 99%

“…Full sequencing of exons and intron-exon boundaries, and MLPA analysis were performed as previously described. 24 England. Mutation screening involves a whole-gene sequencing of exons and intron-exon boundaries, and MLPA analysis for large deletions.…”

Section: Analysis For the 185delag Brca1 Mutationmentioning

confidence: 99%

Haplotype analysis of the 185delAG BRCA1 mutation in ethnically diverse populations

et al. 2012

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The 185delAG* BRCA1 mutation is encountered primarily in Jewish Ashkenazi and Iraqi individuals, and sporadically in non-Jews. Previous studies estimated that this is a founder mutation in Jewish mutation carriers that arose before the dispersion of Jews in the Diaspora B2500 years ago. The aim of this study was to assess the haplotype in ethnically diverse 185delAG* BRCA1 mutation carriers, and to estimate the age at which the mutation arose. Ethnically diverse Jewish and non-Jewish 185delAG*BRCA1 mutation carriers and their relatives were genotyped using 15 microsatellite markers and three SNPs spanning 12.5 MB, encompassing the BRCA1 gene locus. Estimation of mutation age was based on a subset of 11 markers spanning a region of B5 MB, using a previously developed algorithm applying the maximum likelihood method. Overall, 188 participants (154 carriers and 34 noncarriers) from 115 families were included: Ashkenazi, Iraq, Kuchin-Indians, Syria, Turkey, Iran, Tunisia, Bulgaria, non-Jewish English, non-Jewish Malaysian, and Hispanics. Haplotype analysis indicated that the 185delAG mutation arose 750-1500 years ago. In Ashkenazim, it is a founder mutation that arose 61 generations ago, and with a small group of founder mutations was introduced into the Hispanic population (conversos) B650 years ago, and into the Iraqi-Jewish community B450 years ago. The 185delAG mutation in the non-Jewish populations in Malaysia and the UK arose at least twice independently. We conclude that the 185delAG* BRCA1 mutation resides on a common haplotype among Ashkenazi Jews, and arose about 61 generations ago and arose independently at least twice in non-Jews.

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“…This is in part because there have been relatively few studies involving comprehensive analysis of BRCA1 and BRCA2 in Asia, and to date, few Asian countries have had the resources and finances for breast cancer genetic counseling and genetic testing services. Moreover, there have been major challenges in identifying at risk individuals because unlike Caucasian populations where multiplex families and extensive family history are available, the majority of Asian families do not fulfil the typical high risk profile described in other populations because of the lack of accurate reporting of family history of cancer, complex family dynamics and the lower age-standardised rate of breast cancer in Asia [10,11].…”

Section: Introductionmentioning

confidence: 96%

Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families

Kang

Mariapun

Phuah

et al. 2010

Breast Cancer Res Treat

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Early studies of genetic predisposition due to the BRCA1 and BRCA2 genes have focused largely on sequence alterations, but it has now emerged that 4-28% of inherited mutations in the BRCA genes may be due to large genomic rearrangements of these genes. However, to date, there have been relatively few studies of large genomic rearrangements in Asian populations. We have conducted a full sequencing and large genomic rearrangement analysis (using Multiplex Ligation-dependent Probe Amplification, MLPA) of 324 breast cancer patients who were selected from a multi-ethnic hospital-based cohort on the basis of age of onset of breast cancer and/or family history. Three unrelated individuals were found to have large genomic rearrangements: 2 in BRCA1 and 1 in BRCA2, which accounts for 2/24 (8%) of the total mutations detected in BRCA1 and 1/23 (4%) of the mutations in BRCA2 detected in this cohort. Notably, the family history of the individuals with these mutations is largely unremarkable suggesting that family history alone is a poor predictor of mutation status in Asian families. In conclusion, this study in a multi-ethnic (Malay, Chinese, Indian) cohort suggests that large genomic rearrangements are present at a low frequency but should nonetheless be included in the routine testing for BRCA1 and BRCA2.

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Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer

Cited by 78 publications

References 42 publications

Screening of 185DelAG, 1014DelGT and 3889DelAG BRCA1 Mutations in Breast Cancer Patients from North-East India

Screening of 185DelAG, 1014DelGT and 3889DelAG BRCA1 Mutations in Breast Cancer Patients from North-East India

Haplotype analysis of the 185delAG BRCA1 mutation in ethnically diverse populations

Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families

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