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Open Access 01-12-2017 | Research article

Characterization of BRCA1 and BRCA2 variants in multi-ethnic Asian cohort from a Malaysian case-control study

Authors: Kah Nyin Lai, Weang Kee Ho, In Nee Kang, Peter Choon Eng Kang, Sze Yee Phuah, Shivaani Mariapun, Cheng-Har Yip, Nur Aishah Mohd Taib, Soo-Hwang Teo

Published in: BMC Cancer | Issue 1/2017

Abstract

Background

Genetic testing for BRCA1 and BRCA2 has led to the accurate identification of individuals at higher risk of cancer and the development of new therapies. Approximately 10-20% of the genetic testing for BRCA1 and BRCA2 leads to the identification of variants of uncertain significance (VUS), with higher proportions in Asians. We investigated the functional significance of 7 BRCA1 and 25 BRCA2 variants in a multi-ethnic Asian cohort using a case-control approach.

Methods

The MassARRAY genotyping was conducted in 1,394 Chinese, 406 Malay and 310 Indian breast cancer cases and 1,071 Chinese, 167 Malay and 255 Indian healthy controls. The association of individual variant with breast cancer risk was analyzed using logistic regression model adjusted for ethnicity, age and family history.

Results

Our study confirmed BRCA2 p.Ile3412Val is presented in >2% of unaffected women and is likely benign, and BRCA2 p.Ala1996Thr which is predicted to be likely pathogenic by in-silico models is presented in 2% of healthy Indian women suggesting that it may not be associated with breast cancer risk. Single-variant analysis suggests that BRCA1 p.Arg762Ser may be associated with breast cancer risk (OR = 7.4; 95% CI, 0.9–62.3; p = 0.06).

Conclusions

Our study shows that BRCA2 p.Ile3412Val and p.Ala1996Thr are likely benign and highlights the need for population-specific studies to determine the likely functional significance of population-specific variants. Our study also suggests that BRCA1 p.Arg762Ser may be associated with increased risk of breast cancer but other methods or larger studies are required to determine a more precise estimate of breast cancer risk.

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Title: Characterization of BRCA1 and BRCA2 variants in multi-ethnic Asian cohort from a Malaysian case-control study
Authors: Kah Nyin Lai
Weang Kee Ho
In Nee Kang
Peter Choon Eng Kang
Sze Yee Phuah
Shivaani Mariapun
Cheng-Har Yip
Nur Aishah Mohd Taib
Soo-Hwang Teo
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-017-3099-6

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