J Breast Cancer.  2013 Mar;16(1):50-54.

Prevalence of BRCA1 and BRCA2 Germline Mutations in Breast Cancer Women of Multiple Ethnic Region in Northwest China

Affiliations
  • 1Department of Breast Surgery, Xinjiang Cancer Institute & Hospital, Xinjiang Medical University, Urumqi, China.
  • 2Postdoctoral Research Station of Clinical Medicine, Xinjiang Medical University, Urumqi, China.
  • 3Department of Genetics, Medical Center of Groningen University, Groningen, The Netherlands.
  • 4Xinjiang Medical University, Urumqi, China. neuroman@163.com

Abstract

PURPOSE
The aim of this study is to further understand the status of BRCA1 and BRCA2 mutation among Chinese high-risk breast cancer patients in multiple-ethnic regions of China.
METHODS
A total of 79 blood samples of high-risk breast cancer patients from Xinjiang Uyghur autonomous region were analyzed by PCR-DHPLC sequencing analysis.
RESULTS
Analysis with full length of the two genes identified a total of 6 deleterious mutations (2073delA, 2394C-T [Q759X] and IVS16+1G>A in BRCA1; 1627A-T [K467X], 6873delCTCC and 9481delA in BRCA2) in this cohort. The prevalence of BRCA1/2 germline mutation was about 7.6% (6/79) in the Xinjiang multiple ethnic region of China. Among them, 3 novel deleterious mutations, 2073delA in BRCA1 (Han ethnic Chinese) and BRCA2 variants 6873delCTCC and 9481delA (both are Kazakh ethnic Chinese), were identified and they had never been reported in breast cancer information core (BIC) database before. 2394C-T (Q759X) and IVS16+1G>A, in BRCA1 and BRCA2 variants 1627A-T were previously reported in other populations but not Chinese. Among 6 of the BRCA-related tumors, three BRCA1- and one BRCA2-associated tumors were in triple negative (estrogen receptor, progesterone receptor, and HER2 negative expressed) status and exhibited a high tumor grade. So far none of these 6 deleterious mutations were reported in ethnic Han Chinese.
CONCLUSION
BRCA germline mutation in Chinese multiple ethnicity region may exhibit different genotypes compared to ethnic Han Chinese in other regions. These differences may arise from interaction of genetic background and environmental factors.

Keyword

BRCA1; BRCA2; Breast neoplasms; Chinese; Ethnic groups; Genetic variation

MeSH Terms

Asian Continental Ancestry Group
Breast
Breast Neoplasms
China
Cohort Studies
Ethnic Groups
Female
Genetic Variation
Genotype
Germ-Line Mutation
Humans
Prevalence
Receptors, Progesterone
Receptors, Progesterone

Reference

1. The National Bureau of Statistics of China, Department of Population, Social, Science and Technology Statistics. The State Ethnic Affairs Commission of China, Department of Economic Development. Tabulation on Nationalities of 2000 Population Census of China. 2003. Beijing: Nationalities Publishing House.
2. Kwong A, Wong LP, Wong HN, Law FB, Ng EK, Tang YH, et al. Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer. Hugo J. 2009. 3:63–76.
Article
3. Zhang J, Pei R, Pang Z, Ouyang T, Li J, Wang T, et al. Prevalence and characterization of BRCA1 and BRCA2 germline mutations in Chinese women with familial breast cancer. Breast Cancer Res Treat. 2012. 132:421–428.
Article
4. Cao AY, Hu Z, Shao ZM. Mutation screening of breast cancer susceptibility genes in Chinese high-risk families: the results will develop the genetic testing strategy in China. Breast Cancer Res Treat. 2010. 120:271–272.
Article
5. Arnold N, Gross E, Schwarz-Boeger U, Pfisterer J, Jonat W, Kiechle M. A highly sensitive, fast, and economical technique for mutation analysis in hereditary breast and ovarian cancers. Hum Mutat. 1999. 14:333–339.
Article
6. Breast Cancer Information Core. National Human Genome Research Institute. Accessed February 26th, 2013. http://research.nhgri.nih.gov/bic/Member/index.shtml.
7. Newman B, Austin MA, Lee M, King MC. Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families. Proc Natl Acad Sci U S A. 1988. 85:3044–3048.
Article
8. Schildkraut JM, Risch N, Thompson WD. Evaluating genetic association among ovarian, breast, and endometrial cancer: evidence for a breast/ovarian cancer relationship. Am J Hum Genet. 1989. 45:521–529.
9. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science. 1990. 250:1684–1689.
Article
10. Easton DF, Bishop DT, Ford D, Crockford GP. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1993. 52:678–701.
11. Nurwidya F, Takahashi F, Takahashi K. Meeting report: current cancer perspectives from the 9th Annual Meeting of the Japanese Society of Medical Oncology. Thorac Cancer. 2012. 3:94–97.
Article
12. Anglian Breast Cancer Study Group. Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer. 2000. 83:1301–1308.
13. Sng JH, Chang J, Feroze F, Rahman N, Tan W, Lim S, et al. The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives. Br J Cancer. 2000. 82:538–542.
Article
14. Li SS, Tseng HM, Yang TP, Liu CH, Teng SJ, Huang HW, et al. Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan. Hum Genet. 1999. 104:201–204.
Article
15. Song CG, Hu Z, Wu J, Luo JM, Shen ZZ, Huang W, et al. The prevalence of BRCA1 and BRCA2 mutations in eastern Chinese women with breast cancer. J Cancer Res Clin Oncol. 2006. 132:617–626.
Article
16. Yip CH, Taib NA, Choo WY, Rampal S, Thong MK, Teo SH. Clinical and pathologic differences between BRCA1-, BRCA2-, and non-BRCA-associated breast cancers in a multiracial developing country. World J Surg. 2009. 33:2077–2081.
Article
17. Thirthagiri E, Lee SY, Kang P, Lee DS, Toh GT, Selamat S, et al. Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer. Breast Cancer Res. 2008. 10:R59.
Article
18. Ang P, Lim IH, Lee TC, Luo JT, Ong DC, Tan PH, et al. BRCA1 and BRCA2 mutations in an Asian clinic-based population detected using a comprehensive strategy. Cancer Epidemiol Biomarkers Prev. 2007. 16:2276–2284.
Article
19. Foulkes WD, Metcalfe K, Sun P, Hanna WM, Lynch HT, Ghadirian P, et al. Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: the influence of age, grade, and histological type. Clin Cancer Res. 2004. 10:2029–2034.
Article
20. Armes JE, Egan AJ, Southey MC, Dite GS, McCredie MR, Giles GG, et al. The histologic phenotypes of breast carcinoma occurring before age 40 years in women with and without BRCA1 or BRCA2 germline mutations: a population-based study. Cancer. 1998. 83:2335–2345.
Article
21. Choi DH, Lee MH, Bale AE, Carter D, Haffty BG. Incidence of BRCA1 and BRCA2 mutations in young Korean breast cancer patients. J Clin Oncol. 2004. 22:1638–1645.
Article
22. Juwle A, Saranath D. BRCA1/BRCA2 gene mutations/SNPs and BRCA1 haplotypes in early-onset breast cancer patients of Indian ethnicity. Med Oncol. 2012. 29:3272–3281.
Article
23. Han SH, Lee KR, Lee DG, Kim BY, Lee KE, Chung WS. Mutation analysis of BRCA1 and BRCA2 from 793 Korean patients with sporadic breast cancer. Clin Genet. 2006. 70:496–501.
Article
24. Seo JH, Cho DY, Ahn SH, Yoon KS, Kang CS, Cho HM, et al. BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer. Hum Mutat. 2004. 24:350.
Article
25. Ahn SH, Hwang UK, Kwak BS, Yoon HS, Ku BK, Kang HJ, et al. Prevalence of BRCA1 and BRCA2 mutations in Korean breast cancer patients. J Korean Med Sci. 2004. 19:269–274.
Article
26. Yazici H, Bitisik O, Akisik E, Cabioglu N, Saip P, Muslumanoglu M, et al. BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast cancer patients. Br J Cancer. 2000. 83:737–742.
Article
27. Manguoğlu E, Güran S, Yamaç D, Colak T, Simşek M, Baykara M, et al. Germline mutations of BRCA1 and BRCA2 genes in Turkish breast, ovarian, and prostate cancer patients. Cancer Genet Cytogenet. 2010. 203:230–237.
Article
28. Liang Y, Fu D, Hu G. Metadherin: an emerging key regulator of the malignant progression of multiple cancers. Thorac Cancer. 2011. 2:143–148.
Article
29. Chen WQ, Zheng RS, Zeng HM, Zhang SW, Li GL, Wu LY, et al. Incidence and mortality of breast cancer in China, 2008. Thorac Cancer. Epub 2012 Jul 11. DOI: http://dx.doi.org/10.1111/j.1759-7714.2012.00165.x.
Article
30. Iglesias-Garcia J, Lindkvist B, Lariño-Noia J, Domínguez-Muñoz JE. Endoscopic ultrasound elastography. Endosc Ultrasound. 2012. 1:8–16.
Article
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