No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A multi-center cohort study

Timothy R. Rebbeck, Antonis C. Antoniou, Trinidad Caldes Llopis, Heli Nevanlinna, Kristiina Aittomäki, Jacques Simard, Amanda B. Spurdle, Fergus J. Couch, Lutecia H.Mateus Pereira, Mark H. Greene, Irene L. Andrulis, Boris Pasche, Virginia Kaklamani, Ute Hamann, Csilla Szabo, Susan Peock, Margaret Cook, Patricia A. Harrington, Alan Donaldson, Allison M. MaleCarol Anne Gardiner, Helen Gregory, Lucy E. Side, Anne C. Robinson, Louise Emmerson, Ian Ellis, Jean Philippe Peyrat, Joëlle Fournier, Philippe Vennin, Claude Adenis, Danièle Muller, Jean Pierre Fricker, Michel Longy, Olga M. Sinilnikova, Dominique Stoppa-Lyonnet, Rita K. Schmutzler, Beatrix Versmold, Christoph Engel, Alfons Meindl, Karin Kast, Dieter Schaefer, Ursula G. Froster, Georgia Chenevix-Trench, Douglas F. Easton

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background The transforming growth factor β-1 gene (TGFB1) is a plausible candidate for breast cancer susceptibility. The L10P variant of TGFB1 is associated with higher circulating levels and secretion of TGF-β, and recent large-scale studies suggest strongly that this variant is associated with breast cancer risk in the general population. Methods To evaluate whether TGFB1 L10P also modifies the risk of breast cancer in BRCA1 or BRCA2 mutation carriers, we undertook a multi-center study of 3,442 BRCA1 and 2,095 BRCA2 mutation carriers. Results We found no evidence of association between TGFB1 L10P and breast cancer risk in either BRCA1 or BRCA2 mutation carriers. The per-allele HR for the L10P variant was 1.01 (95%CI: 0.92-1.11) in BRCA1 carriers and 0.92 (95%CI: 0.81-1.04) in BRCA2 mutation carriers. Conclusions These results do not support the hypothesis that TGFB1 L10P genotypes modify the risk of breast cancer in BRCA1 or BRCA2 mutation carriers.

Original languageEnglish (US)
Pages (from-to)185-192
Number of pages8
JournalBreast Cancer Research and Treatment
Volume115
Issue number1
DOIs
StatePublished - May 1 2009

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Keywords

  • BRCA1
  • BRCA2
  • Hereditary cancer
  • Risk modifiers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Rebbeck, T. R., Antoniou, A. C., Llopis, T. C., Nevanlinna, H., Aittomäki, K., Simard, J., Spurdle, A. B., Couch, F. J., Pereira, L. H. M., Greene, M. H., Andrulis, I. L., Pasche, B., Kaklamani, V., Hamann, U., Szabo, C., Peock, S., Cook, M., Harrington, P. A., Donaldson, A., ... Easton, D. F. (2009). No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A multi-center cohort study. Breast Cancer Research and Treatment, 115(1), 185-192. https://doi.org/10.1007/s10549-008-0064-8