Advertisement

Breast Cancer Research and Treatment

, Volume 115, Issue 1, pp 145–150 | Cite as

The BARD1 Cys557Ser polymorphism and breast cancer risk: an Australian case–control and family analysis

  • Sharon E. Johnatty
  • Jonathan Beesley
  • Xiaoqing Chen
  • John L. Hopper
  • Melissa C. Southey
  • Graham G. Giles
  • David E. Goldgar
  • Georgia Chenevix-Trench
  • Amanda B. Spurdle
  • The Australian Ovarian Cancer Study Group
  • The Kathleen Cuningham Consortium for Research in Familial Breast Cancer
Epidemiology

Abstract

BARD1 was first identified as a BRCA1-interacting protein with tumour-suppressor functions. Some association studies suggested that the BARD1 Cys557Ser variant might be associated with increased risk of breast cancer, but the evidence remains uncertain. We found that the BARD1 Cys557Ser variant was carried by 50 of 1,136 cases (4.4%) and 30 of 623 controls (5.0%) from the population-based Australian Breast Cancer Family Study, 14 of 324 (4.3%) cases from the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), and 30 of 760 controls (4.0%) from the Australian Ovarian Cancer Study. Case–control comparisons showed no evidence that the variant frequency differed by case–control status (P ≥ 0.3). Segregation analysis of 14 kConFab variant-carrying families containing 157 genotyped individuals provided no evidence of segregation with disease. We conclude that the BARD1 Cys557Ser variant is not associated with breast cancer risk.

Keywords

BARD1 Breast cancer Polymorphisms Cys557Ser 

Notes

Acknowledgements

We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded by NHMRC Grants 145684 and 288704) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. We thank the Margaret McCredie for her role in the establishment of the Australian Breast Cancer Family Study, and we are grateful to the physicians, surgeons and oncologists who endorsed the ABCFS project, the interviewing staff, and the many women who participated in this research. The ABCFS was funded by the National Health and Medical Research Council, the Victorian Health Promotion Foundation, the New South Wales Cancer Council, the Peter MacCallum Cancer Institute, the Inkster-Ross Memorial Fund, and in part by the National Institute of Health, as part of the Cancer Family Registry for Breast Cancer Study (CA 69638). This work used data collected from the Breast Cancer Family Registries Studies (Breast CFRs), funded by the National Cancer Institute under RFA # CA-95-003 and through cooperative agreements with the Fox Chase Cancer Center, Huntsman Cancer Institute, Columbia University, Northern California Cancer Center, Cancer Care Ontario, and University of Melbourne. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CFRs, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the CFRs Centers. This work was supported by funding from the National Health and Medical Research Council (NHMRC). GCT is supported by a NHMRC Senior Principal Research Fellowship, and JH is an NHMRC Australian Fellow. The full AOCS Study Group is listed on (http://www.aocstudy.org/). We gratefully acknowledge the cooperation of all participating institutions and the contributions of the women who participated in this study.

References

  1. 1.
    Bray F, McCarron P, Parkin DM (2004) The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res 6:229–239PubMedCrossRefGoogle Scholar
  2. 2.
    Pharoah PD, Day NE, Duffy S, Easton DF, Ponder BA (1997) Family history and the risk of breast cancer: a systematic review and meta-analysis. Int J Cancer 71:800–809PubMedCrossRefGoogle Scholar
  3. 3.
    Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K (2000) Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85PubMedCrossRefGoogle Scholar
  4. 4.
    Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D, Easton DF, Stratton MR (2007) PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 39:165–167PubMedCrossRefGoogle Scholar
  5. 5.
    Deng CX, Brodie SG (2000) Roles of BRCA1 and its interacting proteins. Bioessays 22:728–737PubMedCrossRefGoogle Scholar
  6. 6.
    Wu LC, Wang ZW, Tsan JT, Spillman MA, Phung A, Xu XL, Yang MC, Hwang LY, Bowcock AM, Baer R (1996) Identification of a RING protein that can interact in vivo with the BRCA1 gene product. Nat Genet 14:430–440PubMedCrossRefGoogle Scholar
  7. 7.
    Westermark UK, Reyngold M, Olshen AB, Baer R, Jasin M, Moynahan ME (2003) BARD1 participates with BRCA1 in homology-directed repair of chromosome breaks. Mol Cell Biol 23:7926–7936PubMedCrossRefGoogle Scholar
  8. 8.
    Brodie SG, Deng CX (2001) BRCA1-associated tumorigenesis: what have we learned from knockout mice? Trends Genet 17:S18–S22PubMedCrossRefGoogle Scholar
  9. 9.
    McCarthy EE, Celebi JT, Baer R, Ludwig T (2003) Loss of Bard1, the heterodimeric partner of the Brca1 tumor suppressor, results in early embryonic lethality and chromosomal instability. Mol Cell Biol 23:5056–5063PubMedCrossRefGoogle Scholar
  10. 10.
    Irminger-Finger I, Soriano JV, Vaudan G, Montesano R, Sappino AP (1998) In vitro repression of Brca1-associated RING domain gene, Bard1, induces phenotypic changes in mammary epithelial cells. J Cell Biol 143:1329–1339PubMedCrossRefGoogle Scholar
  11. 11.
    Thai TH, Du F, Tsan JT, Jin Y, Phung A, Spillman MA, Massa HF, Muller CY, Ashfaq R, Mathis JM, Miller DS, Trask BJ, Baer R, Bowcock AM (1998) Mutations in the BRCA1-associated RING domain (BARD1) gene in primary breast, ovarian and uterine cancers. Hum Mol Genet 7:195–202PubMedCrossRefGoogle Scholar
  12. 12.
    Ghimenti C, Sensi E, Presciuttini S, Brunetti IM, Conte P, Bevilacqua G, Caligo MA (2002) Germline mutations of the BRCA1-associated ring domain (BARD1) gene in breast and breast/ovarian families negative for BRCA1 and BRCA2 alterations. Genes Chromosomes Cancer 33:235–242PubMedCrossRefGoogle Scholar
  13. 13.
    Ishitobi M, Miyoshi Y, Hasegawa S, Egawa C, Tamaki Y, Monden M, Noguchi S (2003) Mutational analysis of BARD1 in familial breast cancer patients in Japan. Cancer Lett 200:1–7PubMedCrossRefGoogle Scholar
  14. 14.
    Karppinen SM, Heikkinen K, Rapakko K, Winqvist R (2004) Mutation screening of the BARD1 gene: evidence for involvement of the Cys557Ser allele in hereditary susceptibility to breast cancer. J Med Genet e41:e114CrossRefGoogle Scholar
  15. 15.
    Sauer MK, Andrulis IL (2005) Identification and characterization of missense alterations in the BRCA1 associated RING domain (BARD1) gene in breast and ovarian cancer. J Med Genet 42:633–638PubMedCrossRefGoogle Scholar
  16. 16.
    Karppinen SM, Barkardottir RB, Backenhorn K, Sydenham T, Syrjakoski K, Schleutker J, Ikonen T, Pylkas K, Rapakko K, Erkko H, Johannesdottir G, Gerdes AM, Thomassen M, Agnarsson BA, Grip M, Kallioniemi A, Kere J, Aaltonen LA, Arason A, Moller P, Kruse TA, Borg A, Winqvist R (2006) Nordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignancies. J Med Genet 43:856–862PubMedCrossRefGoogle Scholar
  17. 17.
    Stacey SN, Sulem P, Johannsson OT, Helgason A, Gudmundsson J, Kostic JP, Kristjansson K, Jonsdottir T, Sigurdsson H, Hrafnkelsson J, Johannsson J, Sveinsson T, Myrdal G, Grimsson HN, Bergthorsson JT, Amundadottir LT, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K (2006) The BARD1 Cys557Ser variant and breast cancer risk in Iceland. PLoS Med 3:e217PubMedCrossRefGoogle Scholar
  18. 18.
    Vahteristo P, Syrjakoski K, Heikkinen T, Eerola H, Aittomaki K, von Smitten K, Holli K, Blomqvist C, Kallioniemi OP, Nevanlinna H (2006) BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition. Eur J Hum Genet 14:167–172PubMedCrossRefGoogle Scholar
  19. 19.
    Jakubowska A, Cybulski C, Szymanska A, Huzarski T, Byrski T, Gronwald J, Debniak T, Gorski B, Kowalska E, Narod SA, Lubinski J (2008) BARD1 and breast cancer in Poland. Breast Cancer Res Treat 107:119–122PubMedCrossRefGoogle Scholar
  20. 20.
    Gorringe KL, Choong DY, Visvader JE, Lindeman GJ, Campbell IG (2007) BARD1 variants are not associated with breast cancer risk in Australian familial breast cancer. Breast Cancer Res Treat. doi: 10.1007/s10549-007-9799-x Google Scholar
  21. 21.
    Hopper JL, Chenevix-Trench G, Jolley DJ, Dite GS, Jenkins MA, Venter DJ, McCredie MR, Giles GG (1999) Design and analysis issues in a population-based, case–control-family study of the genetic epidemiology of breast cancer and the Co-operative Family Registry for Breast Cancer Studies (CFRBCS). J Natl Cancer Inst Monogr 26:95–100Google Scholar
  22. 22.
    Hopper JL, Giles GG, McCredie MRE, Boyle P (1994) Background, rationale and protocol for a case–control-family study of breast cancer. Breast 3:79–86CrossRefGoogle Scholar
  23. 23.
    Mann GJ, Thorne H, Balleine RL, Butow PN, Clarke CL, Edkins E, Evans GM, Fereday S, Haan E, Gattas M, Giles GG, Goldblatt J, Hopper JL, Kirk J, Leary JA, Lindeman G, Niedermayr E, Phillips KA, Picken S, Pupo GM, Saunders C, Scott CL, Spurdle AB, Suthers G, Tucker K, Chenevix-Trench G (2006) Analysis of cancer risk and BRCA1 and BRCA2 mutation prevalence in the kConFab familial breast cancer resource. Breast Cancer Res 8:R12PubMedCrossRefGoogle Scholar
  24. 24.
    Merritt MA, Green AC, Nagle CM, Webb PM (2008) Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer. Int J Cancer 122:170–176PubMedCrossRefGoogle Scholar
  25. 25.
    Seal S, Thompson D, Renwick A, Elliott A, Kelly P, Barfoot R, Chagtai T, Jayatilake H, Ahmed M, Spanova K, North B, McGuffog L, Evans DG, Eccles D, Easton DF, Stratton MR, Rahman N (2006) Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet 38:1239–1241PubMedCrossRefGoogle Scholar
  26. 26.
    Thompson D, Easton DF, Goldgar DE (2003) A full-likelihood method for the evaluation of causality of sequence variants from family data. Am J Hum Genet 73:652–655PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Sharon E. Johnatty
    • 1
  • Jonathan Beesley
    • 1
  • Xiaoqing Chen
    • 1
  • John L. Hopper
    • 2
  • Melissa C. Southey
    • 3
  • Graham G. Giles
    • 4
  • David E. Goldgar
    • 5
  • Georgia Chenevix-Trench
    • 1
  • Amanda B. Spurdle
    • 1
  • The Australian Ovarian Cancer Study Group
    • 1
    • 6
  • The Kathleen Cuningham Consortium for Research in Familial Breast Cancer
    • 6
  1. 1.Cancer and Cell BiologyQueensland Institute of Medical ResearchHerston, BrisbaneAustralia
  2. 2.Centre for Genetic EpidemiologyThe University of MelbourneCarltonAustralia
  3. 3.Department of PathologyThe University of MelbourneCarltonAustralia
  4. 4.Cancer Epidemiology CentreThe Cancer Council VictoriaMelbourneAustralia
  5. 5.Genetic EpidemiologyThe University of UtahSalt Lake CityUSA
  6. 6.Peter MacCallum Cancer CentreMelbourneAustralia

Personalised recommendations