Skip to main content

Advertisement

SpringerLink
Log in

BRCA1 and BRCA2 families and the risk of skin cancer

  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

BRCA1 and BRCA2 mutation carriers have elevated risks of breast and ovarian cancers. The risks for cancers at other sites remain unclear. Melanoma has been associated with BRCA2 mutations in some studies, however, few surveys have included non-melanoma skin cancer. We followed 2729 women with a BRCA1 or BRCA2 mutation for an average of 5.0 years. These women were asked to report new cases of cancer diagnosed in themselves or in their family. The risks of skin cancer were compared for probands with BRCA1 and BRCA2 mutations. Of 1779 women with a BRCA1 mutation, 29 developed skin cancer in the follow-up period (1.6%). Of the 950 women with a BRCA2 mutation, 28 developed skin cancer (3.0%) (OR = 1.83 for BRCA2 versus BRCA1; 95% CI 1.08–3.10; P = 0.02). The odds ratio for basal cell carcinoma was higher (OR = 3.8; 95% CI 1.5–9.4; P = 0.002). BRCA2 mutation carriers are at increased risk for skin cancer, compared with BRCA1 carriers, in particular for basal cell carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ford D, Easton D, Bishop T, Narod S et al (1994) Risk of cancer in BRCA1 mutation carriers. Lancet 343:692–695

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  3. Thompson D, Easton DF (2002) Breast cancer linkage consortium. Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 94:1358–1365

    CAS  PubMed  Google Scholar 

  4. Brose M, Rebbeck T, Calzone K et al (2002) Cancer risk estimates for BRCA1 mutation carriers identified in a cancer risk evaluation program. J Natl Cancer Inst 94:1365–1372

    CAS  PubMed  Google Scholar 

  5. Johannsson O, Loman N, Moller T, Kristoffersson U, Borg A, Olsson H (1999) Incidence of malignant tumors in relatives of BRCA1 and BRCA2 germ-line mutation carriers. Eur J Cancer 35:1248–1257

    Article  CAS  PubMed  Google Scholar 

  6. Bermejo JL, Hemminki K (2004) Risk of cancer at sites other than the breast in Swedish families eligible for BRCA1 or BRCA2 mutation testing. Ann Oncol 15:1834–1841

    Article  Google Scholar 

  7. Shih H, Nathanson K, Seal S, Collins N, Stratton M, Rebbeck T, Weber B (2000) BRCA1 and BRCA2 mutations in breast cancer families with multiple primary cancers. Clin Cancer Res 6:4259–4264

    CAS  PubMed  Google Scholar 

  8. Easton D, Steele L, Fields P, Ormiston W et al (1997) Cancer risks in two large breast cancer families linked to BRCA2 on Chromosome 13q12–13. Am J Hum Genet 61:120–128

    Article  CAS  PubMed  Google Scholar 

  9. Moslehi R, Chu W, Karlan B et al (2000) BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. Am J Hum Genet 66:1259–1272

    Article  CAS  PubMed  Google Scholar 

  10. Risch H, McLaughlin J, Cole D, Rosen B et al (2001) Prevalence of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 68:700–710

    Article  CAS  PubMed  Google Scholar 

  11. Aretini P, D’ Andrea E, Pasini B, Viel A et al (2003) Different expressivity of BRCA1 and BRCA2: analysis of 179 Italian pedigrees with identified mutation. Breast Cancer Res Treat 81:71–79

    Article  CAS  PubMed  Google Scholar 

  12. Streuwing J, Hartge P, Wacholder S et al (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336:1401–1408

    Article  Google Scholar 

  13. Goldgar DE, Easton DF, Cannon-Albright L, Skolnick M (1994) Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst 86:1600–1608

    Article  CAS  PubMed  Google Scholar 

  14. Berman D, Costalas J, Schultz D, Grana G, Daly M, Godwin A (1996) A common mutation in BRCA2 that predisposes to a variety of cancers is found in both Jewish and non-Jewish individuals. Cancer Res 56:3409–3414

    CAS  PubMed  Google Scholar 

  15. Hahn S, Greenhalf B, Ellis I, Sina-Frey M et al (2003) BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst 95:214–221

    Article  CAS  PubMed  Google Scholar 

  16. Murphy K, Brune K, Griffin C, Sollenberger J et al (2002) Evaluation of candidate genes MPP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%. Cancer Res 62:3789–3793

    CAS  PubMed  Google Scholar 

  17. Lal G, Liu G, Schmocker B et al (2000) Inherited predisposition to pancreatic adenocarcinoma: role of family history and germ-line p16, BRCA1 and BRCA2 mutations. Cancer Res 60:409–416

    CAS  PubMed  Google Scholar 

  18. Kirchhoff T, Kauff N, Mitra N et al (2004) BRCA mutations and the risk of prostate cancer in Ashkenazi Jews. Clin Cancer Res 10:2918–2921

    Article  CAS  PubMed  Google Scholar 

  19. Edwards SM, Kote-Jarai Z, Meitz J et al (2003) Two percent of men with early onset prostate cancer harbor germline mutations in the BRCA2 gene. Am J Hum Genet 72:1–12

    Article  CAS  PubMed  Google Scholar 

  20. Vazina A, Baniel J, Shtriker A et al (2000) The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer patients in Israel. Br J Cancer 83:463–466

    Article  CAS  PubMed  Google Scholar 

  21. Hubert A, Peretz T, Manor O et al (1999) The Jewish Ashkenazi founder mutations in the BRCA1/BRCA2 genes are not found at an increased frequency in Ashkenazi patients with prostate cancer. Am J Hum Genet 65:921–924

    Article  CAS  PubMed  Google Scholar 

  22. Thorlacius S, Struewing J, Hartge P et al (1998) Population based study of risk of breast cancer in carriers of BRCA2 mutation. Lancet 352:1337–1339

    Article  CAS  PubMed  Google Scholar 

  23. Sigurdsson S, Thorlaciaus S, Tomasson J et al (1997) BRCA2 mutation in Icelandic prostate cancer patients. J Mol Med 75:758–761

    Article  CAS  PubMed  Google Scholar 

  24. Iscovich J, Abdulrazik M, Cour C et al (2002) Prevalence of the BRCA2 6174 del T mutation in Israeli uveal melanoma patients. Int J Cancer 98:42–44

    Article  CAS  PubMed  Google Scholar 

  25. Scott R, Vajdic C, Armstrong B et al (2002) BRCA2 mutations in a population based series of patients with ocular melanoma. Int J Cancer 102:188–191

    Article  CAS  PubMed  Google Scholar 

  26. Niell B, Rennert G, Bonner J, Almog R, Tomsho L, Gruber S (2004) BRCA1 and BRCA2 founder mutations and the risk of colorectal cancer. J Natl Cancer Inst 96:15–21

    Article  CAS  PubMed  Google Scholar 

  27. Kirchhoff T, Satagopan J, Kauff N et al (2004) Frequency of BRCA1 and BRCA2 mutations in unselected Ashkenazi Jewish patients with colorectal cancer. J Natl Cancer Inst 96:68–70

    Article  CAS  PubMed  Google Scholar 

  28. Chen-Stoyerman R, Figer A, Fidder H et al (2001) The frequency of the predominant Jewish mutations in BRCA1 and BRCA2 in unselected Ashkenazi colorectal cancer patients. Br J Cancer 84:475–477

    Article  Google Scholar 

  29. Drucker L, Stackievitz R, Shpitz B, Yarkoni S (2000) Incidence of BRCA1 and BRCA2 mutations in Ashkenazi colorectal cancer patients: preliminary study. Anticancer Res 20:559–561

    CAS  PubMed  Google Scholar 

  30. Begg CB (2002) On the use of familial aggregation in population-based case probands for calculating penetrance. J Natl Cancer Inst 94:1221–1226

    PubMed  Google Scholar 

  31. Amos CR (2003) Re: on the use of familial aggregation in population-based case probands for calculating penetrance. J Natl Cancer Inst 95:74–75

    Article  CAS  PubMed  Google Scholar 

  32. Risch H, Narod S (2003) Re: on the use of familial aggregation in population-based case probands for calculating penetrance. J Natl Cancer Inst 95:73–74

    CAS  PubMed  Google Scholar 

  33. Pharoah PP, Antoniou A, Hopper J, Easton D (2003) Re: on the use of familial aggregation in population-based case probands for calculating penetrance. J Natl Cancer Inst 95:75–76

    Article  CAS  PubMed  Google Scholar 

  34. Whittemore AS, Gong G (2003) Re: on the use of familial aggregation in population-based case probands for calculating penetrance. J Natl Cancer Inst 95:76–77

    Article  CAS  PubMed  Google Scholar 

  35. Burke W, Austin MA (2003) Re: on the use of familial aggregation in population-based case probands for calculating penetrance. J Natl Cancer Inst 95:78–79

    Article  CAS  PubMed  Google Scholar 

  36. Easton DF, Hopper JL, Thomas DL, Antoniou A, Pharoah PDP, Whittemore AS (2004) Re: breast cancer risks for BRCA1/2 carriers. Science 306:2187–2188

    Article  CAS  PubMed  Google Scholar 

  37. Wacholder S, Struewing JP, Hartage P, Greene MH, Tucker MA (2004) Re: breast cancer risks for BRCA1/2 carriers. Science 306:2188

    CAS  Google Scholar 

  38. King MC, New York Breast Cancer Study Group (2004) Re: breast cancer risks for BRCA1/2 carriers. Science 306:2188–2191

    CAS  Google Scholar 

  39. Offit K (2006) BRCA mutation frequency and penetrance: new data, old debate. J Natl Cancer Inst 98(23):1675–1677

    Article  PubMed  Google Scholar 

  40. Easton DR, Ford D, Bishop DT (1995) Breast and ovarian incidence in BRCA1-mutartion carriers. Am J Hum Genet 56:256–271

    Google Scholar 

  41. Loman N, Bladstrom A, Johannsson O, Borg A, Olsson H (2003) Cancer incidence in relatives of a population-based set of cases of early-onset breast cancer with a known BRCA1 and BRCA2 mutation status. Breast Cancer Res 5:R175–R186

    Article  PubMed  Google Scholar 

  42. Miller DL, Weinstock MA (1994) Nonmelanoma skin cancer in the United States: incidence. J Am Acad Derm 30:774–778

    Article  CAS  PubMed  Google Scholar 

  43. SEER 17 (2000–2006). http://seer.cancer.gov

  44. Levy-Lahad E, Friedman E (2007) Cancer risks among BRCA1 and BRCA2 carriers: minireview. British J Cancer 96:11–15

    Article  CAS  Google Scholar 

  45. Iscovitch J, Abdulrazik M, Cour C et al (2002) Prevalence of the BRCA2 6174delT mutation in uveal melanoma patients. Int J Cancer 98:42–44

    Article  Google Scholar 

  46. Kadouri L, Temper M, Grenader T, Abeliovich D, Hamburger T, Peretz T, Lotem M (2009) Absence of founder BRCA1 and BRCA2 mutations in cutaneous malignant melanoma patients of Ashkenazi origin. Fam Cancer 8:29–32

    Article  CAS  PubMed  Google Scholar 

  47. Monerrat C, Chompret A, Kannengiesser C, Avril M-F et al (2007) BRCA1, BRCA2, CDKN2a germline mutations in patients with breast cancer and cutaneous melanoma. Fam Cancer 6:453–461

    Article  Google Scholar 

  48. Navaraj A, Mori T, El-Deiry WS (2005) Cooperation between BRCA1 and p53 in repair of cyclobutane pyrimidine dimers. Cancer Biol Ther 4:1409–1414

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank David Livingston for helpful discussion. We thank Marcia Llaquachaqui, Anna Tulman and Adriana Valentini for data review and processing. Funded by the Canadian Breast Cancer Research Alliance.

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Medical Oncology, University of Toronto, Toronto, ON, Canada

    Ophira M. Ginsburg

  2. Womens College Research Institute, University of Toronto, 790 Bay Street, 7th Floor, Toronto, ON, M5G 1N8, Canada

    Ophira M. Ginsburg, Ping Sun & Steven A. Narod

  3. BC Cancer Agency, Vancouver, BC, Canada

    Charmaine Kim-Sing

  4. Departments of Medical Oncology and Medical Genetics, McGill University, Montreal, QC, Canada

    William D. Foulkes

  5. Epidemiology Research Unit, Research Centre, Centre Hospitalier de l’Universitaire Montréal, CHUM Hôtel Dieu, Montreal, QC, Canada

    Parviz Ghadirian

  6. Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE, USA

    Henry T. Lynch

  7. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    Steven A. Narod

Authors
  1. Ophira M. Ginsburg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charmaine Kim-Sing
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William D. Foulkes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Parviz Ghadirian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Henry T. Lynch
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ping Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Steven A. Narod
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Hereditary Breast Cancer Clinical Study Group

Corresponding author

Correspondence to Steven A. Narod.

Additional information

Other members of the Hereditary Breast Cancer Clinical Study Group: Olufunmilayo I Olopade, Nadine Tung, Fergus Couch, Barry Rosen, Eitan Friedman, Andrea Eisen, Susan Domchek, Dominique Stoppa-Lyonnet, Ruth Gershoni-Baruch, David Horsman, Teresa Wagner, Howard Saal, Wendy Meschino, Kenneth Offit, Amber Trivedi, Mark Robson, Michael Osborne, Dawna Gilchrist, Charis Eng, Jeffrey Weitzel, Wendy McKinnon, Marie Wood, Barbara Pasini, Peter Ainsworth, Mary Daly, Judy Garber, Kevin Sweet, Taya Fallen, Beth Karlan, Raluca Kurz, Claudine Isaacs, Susan Neuhausen, Siranoush Manoukian, Susan Armel, Rochelle Demsky, Edmond Lemire, Jane Mclennan, Gareth Evans.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ginsburg, O.M., Kim-Sing, C., Foulkes, W.D. et al. BRCA1 and BRCA2 families and the risk of skin cancer. Familial Cancer 9, 489–493 (2010). https://doi.org/10.1007/s10689-010-9377-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-010-9377-y

Keywords

Search

Navigation