BRCA1 and BRCA2 Gene Mutations Screening In Sporadic Breast Cancer Patients In Kazakhstan.

Ainur R. Akilzhanova, Bagdat Nyshanbekkyzy, Zhannur M. Nurkina, Ivan I. Shtephanov, Abay K. Makishev, Tasbolat A. Adylkhanov, Tolebay K. Rakhypbekov, Erlan M. Ramanculov, Kuvat T. Momynaliev

Abstract


Background: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Kazakhstan women.

Aim: To evaluate the role of BRCA1/2 mutations in Kazakhstan women presenting with sporadic breast cancer.

Methods: We investigated the distribution and nature of polymorphisms in BRCA1 and BRCA2 entire coding regions in 156 Kazakhstan sporadic breast cancer cases and 112 age-matched controls using automatic direct sequencing.

Results: We identified 22 distinct variants, including 16 missense mutations and 6 polymorphisms in BRCA1/2 genes. In BRCA1, 9 missense mutations and 3 synonymous polymorphisms were observed. In BRCA2, 7 missense mutations and 3 polymorphisms were detected. There was a higher prevalence of observed mutations in Caucasian breast cancer cases compared to Asian cases (p<0.05); higher frequencies of sequence variants were observed in Asian controls. No recurrent or founder mutations were observed in BRCA1/2 genes. There were no statistically significant differences in age at diagnosis, tumor histology, size of tumor, and lymph node involvement between women with breast cancer with or without the BRCA sequence alterations.

Conclusions:Considering the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of BRCA1/2 mutations and reliable genetic counseling for Kazakhstan sporadic breast cancer patients. Evaluation of common polymorphisms and mutations and breast cancer risk in families with genetic predisposition to breast cancer is ongoing in another current investigation.

 


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Parkin DM, Bray F, Ferlay J, Pisani P. Global Cancer Statistics, 2002. CA Cancer J Clin. 2005; 55 (2): 74–108.

Official site of Ministry of Healthcare, Republic of Kazakhstan, http://www.minzdrav.kz.

Martin AM, Blackwood MA, Antin-Ozerkis D et al. Germline mutations in BRCA1 and BRCA2 in breast-ovarian families from a breast cancer risk evaluation clinic. J Clin Oncol. 2001; 19:2247–2253.

Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, King MC: Linkage of early-onset familial breast cancer to chromosome17q21. Science. 1990; 250:1684-1689.

Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, Nguyen K, Seal S, Tran T, Averill D: Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. 1994; 265:2088-2090.

Scully R, Livingston DM: In Search of the tomour-supperssor function of BRCA1and BRCA2. Nature. 2000; 408:429-432.

Scully R, Puget N, Vlasakova K: DNA polymerase stalling, sister chromatid recombination and the BRCA genes. Oncogenes 2000; 19:6176-6183.

Wang Q, Zhang H, Fishel R, Greene MI: BRCA1 and cell signaling. Oncogene. 2000; 19:6152-6158.

Zhang L, Li S, Boyer TG, Lee WH: Lessons learned from BRCA1 and BRCA2. Oncogene. 2000; 19:6159-6175.

Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH: Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response. Science. 1999; 285:747-750.

Welcsh Piri L, King Mary-Claire: BRCA1 and BRCA2 and genetics of breast and ovarian cancer. Human Molecular Genetics. 2001; 10:7705-713.

Deng CX, Brodie SG. Roles of BRCA1 and its interacting proteins. Bioessays. 2000; 22:728–737.

Seery LT, Knowlden JM, Gee JM, et al. BRCA1 expression levels predict distant metastasis of sporadic breast cancers. Int J Cancer. 1999; 84:258–262.

Wilson CA, Ramos L, Villaseñor MR, et al. Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinoma. Nat Genet. 1999; 21:236–240.

Yoshikawa K, Honda K, Inamoto T, et al. Reduction of BRCA1 protein expression in Japanese sporadic breast carcinomas and its frequent loss in BRCA1-associated cases. Clin Cancer Res. 1999; 5:1249–1261.

Albertsen HM, Smith SA, Mazoyer S, et al. A physical map and candidate genes in the BRCA1 region on chromosome 17q12-21. Nature Genet. 1994; 7:472-479.

O'Connell P, Albertsen H, Matsunami N, et al. A radiation hybrid map of the BRCA1 region. Am J Hum Genet. 1994; 54:526-534.

Matsushima M, Kobayashi K, Emi M, Saito H, Saito J, Suzumori K, Nakamura Y. Mutation analysis of the BRCA1 gene in 76 Japanese ovarian cancer patients: four germline mutations, but no evidence of somatic mutation. Hum Mol Genet. 1996; 4:1953-1956.

De Benedetti VM, Radice P, Mondini P, et al. Screening for mutations in exon 11 of the BRCA1 gene in 70 Italian breast and ovarian cancer patients by protein truncation test. Oncogene. 1996; 13(6):1353-1357.

Katagiri T, Emi M, Ito I, et al. Mutations in the BRCA1 gene in Japanese breast cancer patients. Hum Mutat. 1996; 7:334-339.

Håkansson S, Johannsson O, Johansson U, et al. Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer. Am J Hum Genet. 1997; 60:1068–1078.

Vehmanen P, Friedman LS, Eerola H, McClure M, Ward B, Sarantaus L. Low proportion of BRCA1 and BRCA2 mutations in Finnish breast cancer families: evidence for additional susceptibility genes. Hum Mol Genet. 1997; 6:2309–2315.

Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994; 266:66-71.

Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995; 378:789-92.

Tavtigian SV, Simard J, Rommens J, Couch F, Shattuck-Eidens D, Neuhausen S, et al. The complete BRCA2 gene and mutations in chromosome13q-linked kindreds. Nat Genet. 1996, 12:333-337.

Breast Cancer Information Core database (BIC). Available from: http://research.nhgri.nih.gov/bic.

Narod SA, Goldgar D, Cannon-Albright L et al. Risk modifiers in carriers of BRCA1 mutations. Int J Cancer. 1995; 64: 394–398.

Ford D, Easton DF, Peto J. Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Am J Hum Genet. 1995; 57:1457–1462.

Easton DF, Hopper JL, Thomas DC, Antoniou A, Pharoah PDP, Whittemore A, Haile RW. Breast cancer risks for BRCA1/2 carriers. Science. 2004; 306:2187–2188.

Dunning AM, Chiano M, Smith NR, et al. Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population. Hum Mol Genet. 1997; 6:285–289.

Janezic SA, Ziogas A, Krumroy LM, et al. Germline BRCA1 alterations in a population based series of ovarian cancer cases. Hum Mol Genet. 1999; 8:889–897.

Healey CS, Dunning AM, Teare MD, et al. A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability. Nat Genet. 2000; 26:362–364.

Szabo CI, King MC. Population genetics of BRCA1 and BRCA2. Am J Hum Genet. 1997; 60:1013-1012.

Offit K, Gilewski T, McGuire P, et al. Germline BRCA1 185delAG mutations in Jewish women with breast cancer. Lancet. 1996; 347:1643–1645.

Abeliovich D, Kaduri L, Lerer I, et al. The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-on-set breast cancer patients among Ashkenazi women. Am J Hum Genet. 1997; 60:505-514.

Johannesdottir G, Gudmundsson J, Bergthorsson JT, et al. High prevalence of the 999del5 mutation in Icelandic breast and ovarian cancer patients. Cancer Res. 1996; 56:3663–3665.

De Leon Matsuda ML, Liede A, Kwan E, Mapua CA, Cutiongco EM, Tan A, Borg A, Narod SA. BRCA1 and BRCA2 mutations among breast cancer patients from the Philippines. Int J Cancer. 2002; 98:387–480.

Han SH, Lee KR, Lee DG, Kim DY, Lee KE, Chung WS. Mutation analysis of BRCA1 and BRCA2 from 793 patients with sporadic breast cancer. Clin Genet. 2006, 70:496-501.

Seo JH, Cho DY, Ahn SH, et al. BRCA1 and BRCA2 germline mutations in Korean patients with sporadic cancer. Hum Mutat. 2004; 24:350-356.

Song CG, Hu Z, Wu J, et al. The prevalence of BRCA1 and BRCA2 mutations in eastern Chinese women with breast cancer. J Cancer Res Clin Oncol. 2006; 132:617–26.

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.

Emi M, Matsushima M, Katagiri T, et al. Multiplex mutation screening of the BRCA1 gene in 1000 Japanese breast cancers. Jpn J Cancer Res. 1998; 89(1):12-16.

Sng JH, Chang J, Feroze F, 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.

Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Nat Cancer Inst. 1999; 91:943-9.

Stenson PD; Mort M, Ball EV, Howells K, Phillips AD, Thomas NS, Cooper DN. "The Human Gene Mutation Database: 2008 update". Genome medicine. 2009; 1(1):13.

Akilzhanova A, Meirmanov S, Zhunussova T, Nakashima M, Takamura N, Akanov Zh, et al. Mutational screening of the BRCA1 gene in sporadic breast cancer in the Kazakhstan population. The Breast Journal. 2011; 17(3):328–330.

Tommasi S, Crapolicchio A, Lacalamita R, et al. BRCA1 mutations and polymorphisms in a hospital-based consecutive series of breast cancer patients from Apulia, Italy. Mutation Research. 2005; 578:395–405.

Kim BY, Lee DG, Lee KR, Han SH, Surendran S, Han CW, Chung N. Identification of BRCA1 and BRCA2 mutations from Korean breast cancer patients using denaturating HPLC. J Bioch and Bioph Res Com. 2006; 349:604-610.

Loizidou M, Marcou Y, Anastasiadou V, Newbold R, Hadjisavvas A, Kyriacou K. Contribution of BRCA1 and BRCA2 germline mutations to the incidence of early-onset breast cancer in Cyprus. Clin Genet. 2007; 71:165-170.

The International HapMap Project. Nature. 2003; 426:789–796.

Freedman ML, Penney KL, Stram DO, Riley S, McKean-Cowdin R, Le Marchand L, Altshuler D, Haiman CA. A Haplotype-Based Case-Control Study of BRCA1 and Sporadic Breast Cancer Risk. Cancer Res. 2005; 65(16):7516-7522.

Freedman ML, Penney KL, Stram DO, et al. Common variation in BRCA2 and breast cancer risk: a haplotype based analysis in the Multiethnic Cohort. Hum Mol Genet. 2004; 13:2431–2441.

Cox DG, Kraft P, Hankinson SE, Hunter DJ. Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer. Breast Cancer Res. 2005; 7:R171–175.

Bowcock AM, Kidd JR, Mountain JL, et al. Drift, admixture, and selection in human evolution: a study with DNA polymorphisms. Proc Natl Acad Sci USA. 1991; 88:839–843.

Pike MC, Kolonel LN, Henderson BE, et al. Breast cancer in a multiethnic cohort in Hawaii and Los Angeles: risk factor-adjusted incidence in Japanese equals and in Hawaiians exceeds that in whites. Cancer Epidemiol Biomarkers Prev. 2002; 11:795–800.

Sachidanandam R, Weissman D, Schmidt SC, et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature. 2001; 409:928–933.

Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003; 100:8418–8423.

Foulkes WD, Stefansson IM, Chappuis PO, et al. Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst. 2003; 95:1482–1485.

Turner N, Tutt A, Ashworth A. Hallmarks of ‘‘BRCAness’’ in sporadic cancers. Nat Rev Cancer. 2004; 4:814–819.




DOI: https://doi.org/10.5195/cajgh.2013.29

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