Abstract
Approximately 5–10% of breast cancers are attributable to genetic susceptibility. Mutations in the BRCA1 and BRCA2 genes are the best known genetic factors to date. The goal of this study was to determine the structure and distribution of haplotypes of the BRCA1 and BRCA2 genes in early-onset breast cancer patients. We enrolled 70 patients diagnosed with early-onset breast cancer. A total of 21 SNPs (11 on BRCA1 and 10 on BRCA2) and 1 dinucleotide deletion on BRCA1 were genotyped using nested allele-specific PCR methods. Linkage disequilibrium (LD) analysis was conducted, and haplotypes were deduced from the genotype data. Two tightly linked LD blocks were observed on each of the BRCA1 and BRCA2 genes. Variant-free haplotypes (TAT-AG for BRCA1 and ATA-AAT for BRCA2) were observed at a frequency of more than 50% on each gene along with variable frequencies of derived haplotypes. The variant 3′-subhaplotype CGC displayed strong LD with 5′-subhaplotypes GA, AA, and GG on BRCA1 gene. Haplotypes ATA-AGT, ATC-AAT, and ATA-AAC were the variant haplotypes frequent on BRCA2 gene. Although the clinical significance of these derived haplotypes has not yet been established, it is expected that some of these haplotypes, especially the less frequent subhaplotypes, eventually will be shown to be indicative of a predisposition to early-onset breast cancer.
Mohamed Saleem and Mohd Bazli Ghazali authors contribute to the authorship (as the first author) equally.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Arver, B., Du, Q., Chen, J., Luo, L., & Lindblom, A. (2000). Hereditary breast cancer: A review. Seminars in Cancer Biology, 10, 271–288.
Barrett, J. C., Fry, B., Maller, J., & Daly, M. J. (2005). Haploview: Analysis and visualization of LD and haplotype maps. Bioinformatics, 21, 263–265.
Baynes, C., Healey, C. S., Pooley, K. A., Scollen, S., Luben, R. N., et al. (2007). Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk. Breast Cancer Research, 9, R27.
Beesley, J., Jordan, S. J., Spurdle, A. B., Song, H., Ramus, S. J., et al. (2007). Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: Results from two Australian studies and an additional validation set. Cancer Epidemiology, Biomarkers & Prevention, 16, 2557–2565.
Breast Cancer Association Consortium. (2006). Commonly studied single-nucleotide polymorphisms and breast cancer: Results from the breast cancer association consortium. Journal of the National Cancer Institute, 98, 1382–1396.
Breast Cancer Linkage Consortium. (1997). Pathology of familial breast cancer: Differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Lancet, 349, 1505–1510.
Breast Cancer Linkage Consortium. (1999). Cancer risks in BRCA2 mutation carriers. Journal of the National Cancer Institute, 91, 1310–1316.
Colditz, G. A., Willett, W. C., Hunter, D. J., Stampfer, M. J., Manson, J. E., et al. (1993). Family history, age, and risk of breast cancer. Prospective data from the Nurses’ health study. JAMA, 270, 338–343.
Collaborative Group on Hormonal Factors in Breast Cancer. (2001). Familial breast cancer: Collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet, 358, 1389–1399.
Dahlui, M., Ramli, S., & Bulgiba, A. M. (2011). Breast cancer prevention and control programs in Malaysia. Asian Pacific Journal of Cancer Prevention, 12, 1631–1634.
Frosk, P., Burgess, S., Dyck, T., Jobse, R., & Spriggs, E. L. (2007). The use of ancestral haplotypes in the molecular diagnosis of familial breast cancer. Genetic Testing, 11, 208–215.
Healey, C. S., Dunning, A. M., Teare, M. D., Chase, D., Parker, L., et al. (2000). A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability. Nature Genetics, 26, 362–364.
Landvik, N. E., Hart, K., Skaug, V., Stangeland, L. B., Haugen, A., et al. (2009). A specific interleukin-1B haplotype correlates with high levels of IL1B mRNA in the lung and increased risk of non-small cell lung cancer. Carcinogenesis, 30, 1186–1192.
Lim, G. C. C., Rampal, S., & Halimah, Y. (2008). Cancer incidence in peninsular Malaysia 2003–2005. The third report of the National Cancer Registry Malaysia. Kuala Lumpur: National Cancer Registry, Malaysia.
Loannidis, J. P., Ntzani, E. E., Trikalinos, T. A., & Contopoulos-Ioannidis, D. G. (2001). Replication validity of genetic association studies. Nature Genetics, 29, 306–309.
Madigan, M. P., Ziegler, R. G., Benichou, J., Byrne, C., & Hoover, R. N. (1995). Proportion of breast cancer cases in the United States explained by well-established risk factors. Journal of the National Cancer Institute, 87, 1681–1685.
Palma, M., Ristori, E., Ricevuto, E., Giannini, G., & Gulino, A. (2006). BRCA1 and BRCA2: The genetic testing and the current management options for mutation carriers. Critical Reviews in Oncology/Hematology, 57, 1–23.
Peto, J., Collins, N., Barfoot, R., Seal, S., Warren, W., et al. (1999). Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. Journal of the National Cancer Institute, 91, 943–949.
Qin, Z. S., Niu, T., & Liu, J. S. (2002). Partition-ligation-expectation-maximization algorithm for haplotype inference with single-nucleotide polymorphisms. American Journal of Human Genetics, 71, 1242–1247.
Shen, G. Q., Girelli, D., Li, L., Rao, S., Archacki, S., et al. (2014). A novel molecular diagnostic marker for familial and early-onset CAD and MI in the LRP8 gene. Circulation. Cardiovascular Genetics, 7(4), 514–520.
Slattery, M. L., & Kerber, R. A. (1993). A comprehensive evaluation of family history and breast cancer risk. The Utah population database. JAMA, 270, 1563–1568.
Struewing, J. P., Abeliovich, D., Peretz, T., Avishai, N., Kaback, M. M., et al. (1995). The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nature Genetics, 11, 198–200.
Toh, G. T., Kang, P., Lee, S. S., Lee, D. S., Lee, S. Y., et al. (2008). BRCA1 and BRCA2 germline mutations in Malaysian women with early-onset breast cancer without a family history. PLoS One, 3, e2024.
Wahid, M. I. (2014). Breast cancer. Common cancer. Malaysian Oncological Society. http://www.malaysiaoncology.org/article.php?aid=114
Wooster, R., & Weber, B. L. (2003). Breast and ovarian cancer. The New England Journal of Medicine, 348, 2339–2347.
Acknowledgement
Authors would like to extend nurses and technical staff in the Department of Surgery, Hospital Seberang Jaya, Ministry of Health Malaysia, Hospital Universiti Sains Malaysia (HUSM) and Clinical Trial Centre, and Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia for helping us in sample collection and patient recruitments.
Conflict of Interests
None
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this paper
Cite this paper
Saleem, M. et al. (2018). The BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients. In: Pham, P.V. (eds) Cancer Biology and Advances in Treatment. Advances in Experimental Medicine and Biology(), vol 1292. Springer, Cham. https://doi.org/10.1007/5584_2018_147
Download citation
DOI: https://doi.org/10.1007/5584_2018_147
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-57253-2
Online ISBN: 978-3-030-57254-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)