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, A Donaldson, Allison M MaleCarol Anne Gardiner, Helen Gregory, Lucy E Side, Anne C. Robinson, Louise Emmerson, Ian Ellis, Jean-Philippe Peyrat, Joëlle Fournier, Claude Adenis, Philippe Vennin, 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, kConFaB

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

BACKGROUND: The transforming growth factor beta-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-beta, 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
Pages (from-to)185-192
Number of pages8
JournalBreast Cancer Research and Treatment
Volume115
Issue number1
Early online date4 Jun 2008
DOIs
Publication statusPublished - May 2009

Keywords

  • adult
  • alleles
  • breast neoplasms
  • cohort studies
  • female
  • genes, BRCA1
  • genes, BRCA2
  • genetic predisposition to disease
  • genotype
  • heterozygote
  • humans
  • mutation
  • risk
  • transforming growth factor beta
  • BRCA1
  • BRCA2
  • risk modifiers
  • hereditary cancer

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    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., ... kConFaB (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