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. 2000 Jan;92(1):29–35.

Mutation analysis of BRCA1 gene in African-American patients with breast cancer.

D Shen 1, Y Wu 1, M Subbarao 1, H Bhat 1, R Chillar 1, J V Vadgama 1
PMCID: PMC2640500  PMID: 10800284

Abstract

An estimated 7% of all breast cancers and 10% of all ovarian cancers are associated with inherited mutations in BRCA1 and BRCA2 genes. The mutations of a breast cancer-susceptible gene, BRCA1, confers increased risk of breast cancer in young women. Numerous studies have reported specific mutations in the BRCA1 and BRCA2 genes in the white population. However, there are very few studies on African-American and other ethnic minority groups. The goal of this study is to identify whether African-American patients with breast cancer carry some common mutations reported in other ethnic groups and whether they carry some novel mutations. We screened hot-region mutations on exons 2, 5, 11, 16, and 20 of BRCA1 gene in 54 African-American patients with breast cancer by NIRCA and SSCP methods. Our data revealed one novel frameshift mutation (3331 insG) and three missense sequence variants (A3537G, A3667G, and C4009T) on exon 11. Each sequence change was confirmed by automatic DNA sequencing. One rare sequence variant, A3537G, has been revealed in high frequency (3/54). Our data suggested that African-American patients with breast cancer carry some unique BRCA1 gene mutations.

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Selected References

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  1. Armes J. E., Egan A. J., Southey M. C., Dite G. S., McCredie M. R., Giles G. G., Hopper J. L., Venter D. J. 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 Dec 1;83(11):2335–2345. [PubMed] [Google Scholar]
  2. Blaszyk H., Vaughn C. B., Hartmann A., McGovern R. M., Schroeder J. J., Cunningham J., Schaid D., Sommer S. S., Kovach J. S. Novel pattern of p53 gene mutations in an American black cohort with high mortality from breast cancer. Lancet. 1994 May 14;343(8907):1195–1197. doi: 10.1016/s0140-6736(94)92403-1. [DOI] [PubMed] [Google Scholar]
  3. Chevarley F., White E. Recent trends in breast cancer mortality among white and black US women. Am J Public Health. 1997 May;87(5):775–781. doi: 10.2105/ajph.87.5.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dean M. Resolving DNA mutations. Nat Genet. 1995 Feb;9(2):103–104. doi: 10.1038/ng0295-103. [DOI] [PubMed] [Google Scholar]
  5. Durocher F., Shattuck-Eidens D., McClure M., Labrie F., Skolnick M. H., Goldgar D. E., Simard J. Comparison of BRCA1 polymorphisms, rare sequence variants and/or missense mutations in unaffected and breast/ovarian cancer populations. Hum Mol Genet. 1996 Jun;5(6):835–842. doi: 10.1093/hmg/5.6.835. [DOI] [PubMed] [Google Scholar]
  6. Eley J. W., Hill H. A., Chen V. W., Austin D. F., Wesley M. N., Muss H. B., Greenberg R. S., Coates R. J., Correa P., Redmond C. K. Racial differences in survival from breast cancer. Results of the National Cancer Institute Black/White Cancer Survival Study. JAMA. 1994 Sep 28;272(12):947–954. doi: 10.1001/jama.272.12.947. [DOI] [PubMed] [Google Scholar]
  7. Elledge R. M., Clark G. M., Chamness G. C., Osborne C. K. Tumor biologic factors and breast cancer prognosis among white, Hispanic, and black women in the United States. J Natl Cancer Inst. 1994 May 4;86(9):705–712. doi: 10.1093/jnci/86.9.705. [DOI] [PubMed] [Google Scholar]
  8. FitzGerald M. G., MacDonald D. J., Krainer M., Hoover I., O'Neil E., Unsal H., Silva-Arrieto S., Finkelstein D. M., Beer-Romero P., Englert C. Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer. N Engl J Med. 1996 Jan 18;334(3):143–149. doi: 10.1056/NEJM199601183340302. [DOI] [PubMed] [Google Scholar]
  9. Foulkes W. D., Wong N., Brunet J. S., Bégin L. R., Zhang J. C., Martinez J. J., Rozen F., Tonin P. N., Narod S. A., Karp S. E. Germ-line BRCA1 mutation is an adverse prognostic factor in Ashkenazi Jewish women with breast cancer. Clin Cancer Res. 1997 Dec;3(12 Pt 1):2465–2469. [PubMed] [Google Scholar]
  10. Gao Q., Neuhausen S., Cummings S., Luce M., Olopade O. I. Recurrent germ-line BRCA1 mutations in extended African American families with early-onset breast cancer. Am J Hum Genet. 1997 May;60(5):1233–1236. [PMC free article] [PubMed] [Google Scholar]
  11. Gordon N. H., Crowe J. P., Brumberg D. J., Berger N. A. Socioeconomic factors and race in breast cancer recurrence and survival. Am J Epidemiol. 1992 Mar 15;135(6):609–618. doi: 10.1093/oxfordjournals.aje.a116340. [DOI] [PubMed] [Google Scholar]
  12. Ijaduola T. G., Smith E. B. Pattern of breast cancer among white-American, African-American, and nonimmigrant west-African women. J Natl Med Assoc. 1998 Sep;90(9):547–551. [PMC free article] [PubMed] [Google Scholar]
  13. Johannesdottir G., Gudmundsson J., Bergthorsson J. T., Arason A., Agnarsson B. A., Eiriksdottir G., Johannsson O. T., Borg A., Ingvarsson S., Easton D. F. High prevalence of the 999del5 mutation in icelandic breast and ovarian cancer patients. Cancer Res. 1996 Aug 15;56(16):3663–3665. [PubMed] [Google Scholar]
  14. Johannsson O., Ostermeyer E. A., Håkansson S., Friedman L. S., Johansson U., Sellberg G., Brøndum-Nielsen K., Sele V., Olsson H., King M. C. Founding BRCA1 mutations in hereditary breast and ovarian cancer in southern Sweden. Am J Hum Genet. 1996 Mar;58(3):441–450. [PMC free article] [PubMed] [Google Scholar]
  15. Lakhani S. R., Jacquemier J., Sloane J. P., Gusterson B. A., Anderson T. J., van de Vijver M. J., Farid L. M., Venter D., Antoniou A., Storfer-Isser A. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst. 1998 Aug 5;90(15):1138–1145. doi: 10.1093/jnci/90.15.1138. [DOI] [PubMed] [Google Scholar]
  16. Landis S. H., Murray T., Bolden S., Wingo P. A. Cancer statistics, 1998. CA Cancer J Clin. 1998 Jan-Feb;48(1):6–29. doi: 10.3322/canjclin.48.1.6. [DOI] [PubMed] [Google Scholar]
  17. Langston A. A., Malone K. E., Thompson J. D., Daling J. R., Ostrander E. A. BRCA1 mutations in a population-based sample of young women with breast cancer. N Engl J Med. 1996 Jan 18;334(3):137–142. doi: 10.1056/NEJM199601183340301. [DOI] [PubMed] [Google Scholar]
  18. Lannin D. R., Mathews H. F., Mitchell J., Swanson M. S., Swanson F. H., Edwards M. S. Influence of socioeconomic and cultural factors on racial differences in late-stage presentation of breast cancer. JAMA. 1998 Jun 10;279(22):1801–1807. doi: 10.1001/jama.279.22.1801. [DOI] [PubMed] [Google Scholar]
  19. Malone K. E., Daling J. R., Thompson J. D., O'Brien C. A., Francisco L. V., Ostrander E. A. BRCA1 mutations and breast cancer in the general population: analyses in women before age 35 years and in women before age 45 years with first-degree family history. JAMA. 1998 Mar 25;279(12):922–929. doi: 10.1001/jama.279.12.922. [DOI] [PubMed] [Google Scholar]
  20. Merajver S. D., Pham T. M., Caduff R. F., Chen M., Poy E. L., Cooney K. A., Weber B. L., Collins F. S., Johnston C., Frank T. S. Somatic mutations in the BRCA1 gene in sporadic ovarian tumours. Nat Genet. 1995 Apr;9(4):439–443. doi: 10.1038/ng0495-439. [DOI] [PubMed] [Google Scholar]
  21. Miki Y., Swensen J., Shattuck-Eidens D., Futreal P. A., Harshman K., Tavtigian S., Liu Q., Cochran C., Bennett L. M., Ding W. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994 Oct 7;266(5182):66–71. doi: 10.1126/science.7545954. [DOI] [PubMed] [Google Scholar]
  22. Neuhausen S., Gilewski T., Norton L., Tran T., McGuire P., Swensen J., Hampel H., Borgen P., Brown K., Skolnick M. Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer. Nat Genet. 1996 May;13(1):126–128. doi: 10.1038/ng0596-126. [DOI] [PubMed] [Google Scholar]
  23. Newman B., Mu H., Butler L. M., Millikan R. C., Moorman P. G., King M. C. Frequency of breast cancer attributable to BRCA1 in a population-based series of American women. JAMA. 1998 Mar 25;279(12):915–921. doi: 10.1001/jama.279.12.915. [DOI] [PubMed] [Google Scholar]
  24. Oddoux C., Struewing J. P., Clayton C. M., Neuhausen S., Brody L. C., Kaback M., Haas B., Norton L., Borgen P., Jhanwar S. The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1%. Nat Genet. 1996 Oct;14(2):188–190. doi: 10.1038/ng1096-188. [DOI] [PubMed] [Google Scholar]
  25. Offit K., Gilewski T., McGuire P., Schluger A., Hampel H., Brown K., Swensen J., Neuhausen S., Skolnick M., Norton L. Germline BRCA1 185delAG mutations in Jewish women with breast cancer. Lancet. 1996 Jun 15;347(9016):1643–1645. doi: 10.1016/s0140-6736(96)91484-1. [DOI] [PubMed] [Google Scholar]
  26. Peelen T., van Vliet M., Petrij-Bosch A., Mieremet R., Szabo C., van den Ouweland A. M., Hogervorst F., Brohet R., Ligtenberg M. J., Teugels E. A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families. Am J Hum Genet. 1997 May;60(5):1041–1049. [PMC free article] [PubMed] [Google Scholar]
  27. Roa B. B., Boyd A. A., Volcik K., Richards C. S. Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet. 1996 Oct;14(2):185–187. doi: 10.1038/ng1096-185. [DOI] [PubMed] [Google Scholar]
  28. Shiao Y. H., Chen V. W., Scheer W. D., Wu X. C., Correa P. Racial disparity in the association of p53 gene alterations with breast cancer survival. Cancer Res. 1995 Apr 1;55(7):1485–1490. [PubMed] [Google Scholar]
  29. Struewing J. P., Abeliovich D., Peretz T., Avishai N., Kaback M. M., Collins F. S., Brody L. C. The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nat Genet. 1995 Oct;11(2):198–200. doi: 10.1038/ng1095-198. [DOI] [PubMed] [Google Scholar]
  30. Szabo C. I., Wagner L. A., Francisco L. V., Roach J. C., Argonza R., King M. C., Ostrander E. A. Human, canine and murine BRCA1 genes: sequence comparison among species. Hum Mol Genet. 1996 Sep;5(9):1289–1298. doi: 10.1093/hmg/5.9.1289. [DOI] [PubMed] [Google Scholar]
  31. Tonin P., Weber B., Offit K., Couch F., Rebbeck T. R., Neuhausen S., Godwin A. K., Daly M., Wagner-Costalos J., Berman D. Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families. Nat Med. 1996 Nov;2(11):1179–1183. doi: 10.1038/nm1196-1179. [DOI] [PubMed] [Google Scholar]
  32. Verhoog L. C., Brekelmans C. T., Seynaeve C., van den Bosch L. M., Dahmen G., van Geel A. N., Tilanus-Linthorst M. M., Bartels C. C., Wagner A., van den Ouweland A. Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet. 1998 Jan 31;351(9099):316–321. doi: 10.1016/s0140-6736(97)07065-7. [DOI] [PubMed] [Google Scholar]
  33. Wojcik B. E., Spinks M. K., Optenberg S. A. Breast carcinoma survival analysis for African American and white women in an equal-access health care system. Cancer. 1998 Apr 1;82(7):1310–1318. doi: 10.1002/(sici)1097-0142(19980401)82:7<1310::aid-cncr14>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]

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