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High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia

  • Epidemiology
  • Published:
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Abstract

In South America, a high proportion of the population is of Hispanic origin with an important representation in Colombia. Since nothing is known about the contribution of BRCA1 and BRCA2 germline mutations to hereditary breast/ovarian cancer in the Hispanic population from Colombia, we conducted the first study of 53 breast/ovarian cancer families from this country. Comprehensive BRCA mutation screening was performed using a range of techniques, including DHPLC, SSCP, and PTT, followed by DNA sequencing analysis. Thirteen deleterious germline mutations (24.5%) were identified in 53 families, comprising eight in BRCA1 and five in BRCA2. The two recurrent BRCA1 mutations, 3450 delCAAG and A1708E, accounted for 100% of all BRCA1 mutations identified in this cohort and the recurrent 3034 delACAA BRCA2 mutation for 40% of all BRCA2 mutations. Haplotype analyses suggested that each of these mutations has arisen from a common ancestor. The prevalence of BRCA1 or BRCA2 mutations was 50% in multiple case breast cancer families, and was 33% for the breast-ovarian cancer families. Our findings show that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer in Colombia. The spectrum of mutations differed completely to that previously reported in Hispanic families of predominantly Mexican origin from Southern California [1] suggesting that specific genetic risk assessment strategies for the different Hispanic populations in South America and in the United States need to be developed.

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Fig. 1

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Abbreviations

SSCP:

Single strand conformational polymorphism

PTT:

Protein truncation test

DHPLC:

Denaturing high-pressure liquid chromatography

References

  1. Weitzel JN, Lagos V, Blazer KR, Nelson R, Ricker C, Herzog J, McGuire C, Neuhausen S (2005) Prevalence of BRCA mutations and founder effect in high-risk Hispanic families. Cancer Epidemiol Biomarkers Prev 14:1666–1671

    Article  PubMed  CAS  Google Scholar 

  2. Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J (1997) Cancer incidence in five continents. IARC Scientific Publications No.143, Lyon, France, p. 7

  3. Claus EB, Schildkraut JM, Thompson WD, Risch NJ (1996) The genetic attributable risk of breast and ovarian cancer. Cancer 77:2318–2324

    Article  PubMed  CAS  Google Scholar 

  4. Rebbeck TR, Couch FJ, Kant J, Calzone K, DeShano M, Peng Y, Chen K, Garber JE, Weber BL (1996) Genetic heterogeneity in hereditary breast cancer: role of BRCA1 and BRCA2. Am J Hum Genet 59:547–553

    PubMed  CAS  Google Scholar 

  5. Narod S, Ford D, Devilee P, Barkardottir RB, Eyfjord J, Lenoir G, Serova O, Easton D, Goldgar D (1995) Genetic heterogeneity of breast-ovarian cancer revisited. Am J Hum Genet 57:957–958

    PubMed  CAS  Google Scholar 

  6. Narod SA, Ford D, Devilee P, Barkardottir RB, Lynch HT, Smith SA, Ponder BAJ, Weber BL, Garber JE, Birch JM, Cornelis RS, Kelsell DP, Spurr NK, Smyth E, Haites N, Sobol H, Bignon Y-J, Chang-Claude J, Hamann U, Lindblom A, Borg A, Piver MS, Gallion HH, Struewing JP, Whittemore A, Tonin P, Goldgar DE, Easton DF, the Breast Cancer Linkage Consortium (1995) An evaluation of genetic heterogeneity in 145 breast-ovarian cancer families. Am J Hum Genet 56:254–264

    Google Scholar 

  7. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BA, Gayther SA, Zelada-Hedman M, the Breast Cancer Linkage Consortium (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am J Hum Genet 62:676–689

    Google Scholar 

  8. Satagopan JM, Offit K, Foulkes W, Robson ME, Wacholder S, Eng CM, Karp SE, Begg CB (2001) The lifetime risks of breast cancer in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev 10:467–473

    PubMed  CAS  Google Scholar 

  9. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE (1994) Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 343:692–695

    Article  PubMed  CAS  Google Scholar 

  10. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjakoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72:1117–1130

    Article  PubMed  CAS  Google Scholar 

  11. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Kwan E, Jack E, Vesprini DJ, Kuperstein G, Abrahamson JL, Fan I, Wong B, Narod SA (2001) Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 68:700–710

    Article  PubMed  CAS  Google Scholar 

  12. Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, Timmerman MM, Brody LC, Tucker MA (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336:1401–1408

    Article  PubMed  CAS  Google Scholar 

  13. Antoniou AC, Gayther SA, Stratton JF, Ponder BA, Easton DF (2000) Risk models for familial ovarian and breast cancer. Genet Epidemiol 18:173–190

    Article  PubMed  CAS  Google Scholar 

  14. The Breast Cancer Linkage Consortium (1999) Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 91:1310–1316

    Article  Google Scholar 

  15. Liede A, Narod SA (2002) Hereditary breast and ovarian cancer in Asia: genetic epidemiology of BRCA1 and BRCA2. Hum Mutat 20:413–424

    Article  PubMed  CAS  Google Scholar 

  16. Hamann U, Brauch H, Garvin AM, Bastert G, Scott RJ (1997) German family study on hereditary breast and/or ovarian cancer: germline mutation analysis of the BRCA1 gene. Genes Chromosomes Cancer 18:126–132

    Article  PubMed  CAS  Google Scholar 

  17. Hamann U, Liu X, Lange S, Ulmer HU, Benner A, Scott RJ (2002) Contribution of BRCA2 germline mutations to hereditary breast/ovarian cancer in Germany. J Med Genet 39:E12

    Article  PubMed  CAS  Google Scholar 

  18. Arnold N, Gross E, Schwarz-Boeger U, Pfisterer J, Jonat W, Kiechle M (1999) A highly sensitive, fast, and economical technique for mutation analysis in hereditary breast and ovarian cancers. Hum Mutat 14:333–339

    Article  PubMed  CAS  Google Scholar 

  19. Gross E, Arnold N, Pfeifer K, Bandick K, Kiechle M (2000) Identification of specific BRCA1 and BRCA2 variants by DHPLC. Hum Mutat 16:345–353

    Article  PubMed  CAS  Google Scholar 

  20. Neuhausen SL, Mazoyer S, Friedman L, Stratton M, Offit K, Caligo A, Tomlinson G, Cannon-Albright L, Bishop T, Kelsell D, Solomon E, Weber B, Couch F, Struewing J, Tonin P, Durocher F, Narod S, Skolnick MH, Lenoir G, Serova O, Ponder B, Stoppa-Lyonnet D, Easton D, King MC, Goldgar DE (1996) Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study. Am J Hum Genet 58:271–280

    PubMed  CAS  Google Scholar 

  21. Neuhausen SL, Godwin AK, Gershoni-Baruch R, Schubert E, Garber J, Stoppa-Lyonnet D, Olah E, Csokay B, Serova O, Lalloo F, Osorio A, Stratton M, Offit K, Boyd J, Caligo MA, Scott RJ, Schofield A, Teugels E, Schwab M, Cannon-Albright L, Bishop T, Easton D, Benitez J, King MC, Goldgar D (1998) Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study. Am J Hum Genet 62:1381–1388

    Article  PubMed  CAS  Google Scholar 

  22. Agresti A, Coull BA (1998) Approximate is better than “exact” for interval estimation of binomial proportions. Am Stat 52:119–126

    Article  Google Scholar 

  23. Mazoyer S, Dunning AM, Serova O, Dearden J, Puget N, Healey CS, Gayther SA, Mangion J, Stratton MR, Lynch HT, Goldgar DE, Ponder BA, Lenoir GM (1996) A polymorphic stop codon in BRCA2. Nat Genet 14:253–254

    Article  PubMed  CAS  Google Scholar 

  24. Jara L, Ampuero S, Santibanez E, Seccia L, Rodriguez J, Lay-Son MB, Ojeda JM, Reyes JM, Blanco R (2004) Molecular analysis of the eighteen most frequent mutations in the BRCA1 gene in 63 Chilean breast cancer families. Biol Res 37:469–481

    Article  PubMed  CAS  Google Scholar 

  25. Gallardo M, Silva A, Rubio L, Alvarez C, Torrealba C, Salinas M, Tapia T, Faundez P, Palma L, Riccio ME, Paredes H, Rodriguez M, Cruz A, Rousseau C, King MC, Camus M, Alvarez M, Carvallo P (2005) Incidence of BRCA1 and BRCA2 mutations in 54 Chilean families with breast/ovarian cancer, genotype-phenotype correlations. Breast Cancer Res Treat 95:81–87

    Article  PubMed  CAS  Google Scholar 

  26. Ruiz-Flores P, Sinilnikova OM, Badzioch M, Calderon-Garciduenas AL, Chopin S, Fabrice O, Gonzalez-Guerrero JF, Szabo C, Lenoir G, Goldgar DE, Barrera-Saldana HA (2002) BRCA1 and BRCA2 mutation analysis of early-onset and familial breast cancer cases in Mexico. Hum Mutat 20:474–475

    Article  PubMed  Google Scholar 

  27. Goelen G, Teugels E, Bonduelle M, Neyns B, De Greve J (1999) High frequency of BRCA1/2 germline mutations in 42 Belgian families with a small number of symptomatic subjects. J Med Genet 36:304–308

    PubMed  CAS  Google Scholar 

  28. Santarosa M, Dolcetti R, Magri MD, Crivellari D, Tibiletti MG, Gallo A, Tumolo S, Della Puppa L, Furlan D, Boiocchi M, Viel A (1999) BRCA1 and BRCA2 genes: role in hereditary breast and ovarian cancer in Italy. Int J Cancer 83:5–9

    Article  PubMed  CAS  Google Scholar 

  29. Hakansson S, Johannsson O, Johansson U, Sellberg G, Loman N, Gerdes AM, Holmberg E, Dahl N, Pandis N, Kristoffersson U, Olsson H, Borg A (1997) Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer. Am J Hum Genet 60:1068–1078

    PubMed  CAS  Google Scholar 

  30. Frank TS, Manley SA, Olopade OI, Cummings S, Garber JE, Bernhardt B, Antman K, Russo D, Wood ME, Mullineau L, Isaacs C, Peshkin B, Buys S, Venne V, Rowley PT, Loader S, Offit K, Robson M, Hampel H, Brener D, Winer EP, Clark S, Weber B, Strong LC, Thomas A (1998) Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. J Clin Oncol 16:2417–2425

    PubMed  CAS  Google Scholar 

  31. Ikeda N, Miyoshi Y, Yoneda K, Shiba E, Sekihara Y, Kinoshita M, Noguchi S (2001) Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. Int J Cancer 91:83–88

    Article  PubMed  CAS  Google Scholar 

  32. Yazici H, Bitisik O, Akisik E, Cabioglu N, Saip P, Muslumanoglu M, Glendon G, Bengisu E, Ozbilen S, Dincer M, Turkmen S, Andrulis IL, Dalay N, Ozcelik H (2000) BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast cancer patients. Br J Cancer 83:737–742

    Article  PubMed  CAS  Google Scholar 

  33. Caldes T, de la Hoya M, Tosar A, Sulleiro S, Godino J, Ibanez D, Martin M, Perez-Segura P, Diaz-Rubio E (2002) A breast cancer family from Spain with germline mutations in both the BRCA1 and BRCA2 genes. J Med Genet 39:e44

    Article  PubMed  CAS  Google Scholar 

  34. De la Hoya M, Sulleiro S, Osorio A, Diez O, Baiget M, Benitez J, Diaz-Rubio E, Caldes T (2002) Clustering of cancer-related mutations in a subset of BRCA1 alleles: a study in the Spanish population. Int J Cancer 100:618–619

    Article  CAS  Google Scholar 

  35. Diez O, Osorio A, Duran M, Martinez-Ferrandis JI, De La HM, Salazar R, Vega A, Campos B, Rodriguez-Lopez R, Velasco E, Chaves J, Diaz-Rubio E, Jesus CJ, Torres M, Esteban E, Cervantes A, Alonso C, San Roman JM, Gonzalez-Sarmiento R, Miner C, Carracedo A, Eugenia AM, Caldes T, Benitez J, Baiget M (2003) Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects. Hum Mutat 22:301–312

    Article  PubMed  CAS  Google Scholar 

  36. Liede A, Malik IA, Aziz Z, Rios Pd PL, Kwan E, Narod SA (2002) Contribution of BRCA1 and BRCA2 mutations to breast and ovarian cancer in Pakistan. Am J Hum Genet 71:595–606

    Article  PubMed  CAS  Google Scholar 

  37. Rashid MU, Zaidi A, Torres D, Sultan F, Benner A, Naqvi B, Shakoori AR, Seidel-Renkert A, Farooq H, Narod S, Amin A, Hamann U (2006) Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer patients. Int J Cancer, in press

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Acknowledgements

We are grateful to all family members for their participation in this study. We thank Jaime Bernal for his support in the recruitment of families. We thank Alberto Gómez for critical discussions and reading of the manuscript, Bernd Arnold and Dieter Niederacher for DNA samples of BRCA1/2 mutation controls and advice for DHPLC analysis, Ana Osorio for providing a DNA sample of a Spanish A1708E mutation carrier, and Antje Seidel-Renkert and Michael Gilbert for expert technical assistance. This work was supported by the Deutsches Krebsforschungszentrum, Heidelberg and the Pontificia Universidad Javeriana, Bogotá. Diana Torres was a guest researcher from the Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia in the DKFZ, Heidelberg, supported by a fellowship from the DAAD, Germany, and by a special funding of the Vicerrectoría Académica, Pontificia Universidad Javeriana, Bogotá, Colombia.

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Authors and Affiliations

  1. Division of Molecular Genome Analysis, German Cancer Research Center, Im Neuenheimer Feld 580, 69120, Heidelberg, Germany

    Diana Torres, Muhammad Usman Rashid & Ute Hamann

  2. Unidad de Epidemiología Clínica y Bioestadística, Pontificia Universidad Javeriana, Bogotá, Colombia

    Fabian Gil

  3. Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia

    Diana Torres, Angela Umana, Giancarlo Ramelli & Ignacio Briceno

  4. Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan

    Muhammad Usman Rashid

  5. Departamento de Cirugía, Clínica del Country, Bogotá, Colombia

    Jose Fernando Robledo

  6. Facultad de Medicina, Departamento de Cirugía, Pontificia Universidad Javeriana, Bogotá, Colombia

    Mauricio Tawil & Lilian Torregrosa

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  1. Diana Torres
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  2. Muhammad Usman Rashid
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  10. Ute Hamann
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Correspondence to Ute Hamann.

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Torres, D., Rashid, M., Gil, F. et al. High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia. Breast Cancer Res Treat 103, 225–232 (2007). https://doi.org/10.1007/s10549-006-9370-1

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  • DOI: https://doi.org/10.1007/s10549-006-9370-1

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