Advertisement

The BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients

  • Mohamed Saleem
  • Mohd Bazli Ghazali
  • Md Azlan Mohamed Abdul Wahab
  • Narazah Mohd Yusoff
  • Hakimah Mahsin
  • Ch’ng Ewe Seng
  • Imran Abdul Khalid
  • Mohd Nor Gohar Rahman
  • Badrul Hisham YahayaEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1292)

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.

Keywords

BRCA1 BRCA2 Breast cancer Early onset 

Notes

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

References

  1. Arver, B., Du, Q., Chen, J., Luo, L., & Lindblom, A. (2000). Hereditary breast cancer: A review. Seminars in Cancer Biology, 10, 271–288.CrossRefGoogle Scholar
  2. Barrett, J. C., Fry, B., Maller, J., & Daly, M. J. (2005). Haploview: Analysis and visualization of LD and haplotype maps. Bioinformatics, 21, 263–265.CrossRefGoogle Scholar
  3. 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.CrossRefPubMedCentralGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.CrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. Breast Cancer Linkage Consortium. (1999). Cancer risks in BRCA2 mutation carriers. Journal of the National Cancer Institute, 91, 1310–1316.CrossRefGoogle Scholar
  8. 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.CrossRefGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 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.PubMedPubMedCentralGoogle Scholar
  11. 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.CrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.Google Scholar
  15. 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.CrossRefGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.CrossRefPubMedCentralGoogle Scholar
  20. 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.CrossRefPubMedCentralGoogle Scholar
  21. 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.CrossRefPubMedCentralGoogle Scholar
  22. 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.CrossRefGoogle Scholar
  23. 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.CrossRefPubMedCentralGoogle Scholar
  24. Wahid, M. I. (2014). Breast cancer. Common cancer. Malaysian Oncological Society. http://www.malaysiaoncology.org/article.php?aid=114
  25. Wooster, R., & Weber, B. L. (2003). Breast and ovarian cancer. The New England Journal of Medicine, 348, 2339–2347.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Mohamed Saleem
    • 1
    • 2
  • Mohd Bazli Ghazali
    • 1
    • 5
  • Md Azlan Mohamed Abdul Wahab
    • 1
  • Narazah Mohd Yusoff
    • 1
  • Hakimah Mahsin
    • 3
  • Ch’ng Ewe Seng
    • 4
  • Imran Abdul Khalid
    • 5
  • Mohd Nor Gohar Rahman
    • 6
  • Badrul Hisham Yahaya
    • 1
    Email author
  1. 1.Regenerative Medicine Cluster, Advanced Medical and Dental InstituteUniversiti Sains MalaysiaPenangMalaysia
  2. 2.Genomix Lab Sdn BhdPetaling JayaMalaysia
  3. 3.Pathology DepartmentSeberang Jaya HospitalSeberang PraiMalaysia
  4. 4.Oncology and Radiological Sciences Cluster, Advanced Medical and Dental InstituteUniversiti Sains MalaysiaPenangMalaysia
  5. 5.Surgery DepartmentSeberang Jaya HospitalSeberang PraiMalaysia
  6. 6.Surgery Department, School of Medical SciencesUniversiti Sains MalaysiaKubang KerianMalaysia

Personalised recommendations