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

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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

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Transforming Growth Factor beta
Cohort Studies
Genotype
Breast Neoplasms
Mutation
Genes
Alleles
Population

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

Cite this

No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers : a multi-center cohort study. / Rebbeck, Timothy R; Antoniou, Antonis C; Llopis, Trinidad Caldes; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Spurdle, Amanda B; Couch, Fergus J; Pereira, Lutecia H Mateus; Greene, Mark H; Andrulis, Irene L; Pasche, Boris; Kaklamani, Virginia; Hamann, Ute; Szabo, Csilla; Peock, Susan; Cook, Margaret; Harrington, Patricia A. ; Donaldson, A; Male, Allison M; Gardiner, Carol Anne; Gregory, Helen; Side, Lucy E; Robinson, Anne C. ; Emmerson, Louise; Ellis, Ian; Peyrat, Jean-Philippe; Fournier, Joëlle; Adenis, Claude; Vennin, Philippe; Muller, Danièle; Fricker, Jean-Pierre; Longy, Michel; Sinilnikova, Olga M; Stoppa-Lyonnet, Dominique; Schmutzler, Rita K; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Kast, Karin; Schaefer, Dieter; Froster, Ursula G; Chenevix-Trench, Georgia; Easton, Douglas F; kConFaB.

In: Breast Cancer Research and Treatment, Vol. 115, No. 1, 05.2009, p. 185-192.

Research output: Contribution to journalArticle

Rebbeck, TR, Antoniou, AC, Llopis, TC, Nevanlinna, H, Aittomäki, K, Simard, J, Spurdle, AB, Couch, FJ, Pereira, LHM, Greene, MH, Andrulis, IL, Pasche, B, Kaklamani, V, Hamann, U, Szabo, C, Peock, S, Cook, M, Harrington, PA, Donaldson, A, Male, AM, Gardiner, CA, Gregory, H, Side, LE, Robinson, AC, Emmerson, L, Ellis, I, Peyrat, J-P, Fournier, J, Adenis, C, Vennin, P, Muller, D, Fricker, J-P, Longy, M, Sinilnikova, OM, Stoppa-Lyonnet, D, Schmutzler, RK, Versmold, B, Engel, C, Meindl, A, Kast, K, Schaefer, D, Froster, UG, Chenevix-Trench, G, Easton, DF & 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, vol. 115, no. 1, pp. 185-192. https://doi.org/10.1007/s10549-008-0064-8
Rebbeck, Timothy R ; Antoniou, Antonis C ; Llopis, Trinidad Caldes ; Nevanlinna, Heli ; Aittomäki, Kristiina ; Simard, Jacques ; Spurdle, Amanda B ; Couch, Fergus J ; Pereira, Lutecia H Mateus ; Greene, Mark H ; Andrulis, Irene L ; Pasche, Boris ; Kaklamani, Virginia ; Hamann, Ute ; Szabo, Csilla ; Peock, Susan ; Cook, Margaret ; Harrington, Patricia A. ; Donaldson, A ; Male, Allison M ; Gardiner, Carol Anne ; Gregory, Helen ; Side, Lucy E ; Robinson, Anne C. ; Emmerson, Louise ; Ellis, Ian ; Peyrat, Jean-Philippe ; Fournier, Joëlle ; Adenis, Claude ; Vennin, Philippe ; Muller, Danièle ; Fricker, Jean-Pierre ; Longy, Michel ; Sinilnikova, Olga M ; Stoppa-Lyonnet, Dominique ; Schmutzler, Rita K ; Versmold, Beatrix ; Engel, Christoph ; Meindl, Alfons ; Kast, Karin ; Schaefer, Dieter ; Froster, Ursula G ; Chenevix-Trench, Georgia ; Easton, Douglas F ; kConFaB. / No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers : a multi-center cohort study. In: Breast Cancer Research and Treatment. 2009 ; Vol. 115, No. 1. pp. 185-192.
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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.",
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TY - JOUR

T1 - No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers

T2 - a multi-center cohort study

AU - Rebbeck, Timothy R

AU - Antoniou, Antonis C

AU - Llopis, Trinidad Caldes

AU - Nevanlinna, Heli

AU - Aittomäki, Kristiina

AU - Simard, Jacques

AU - Spurdle, Amanda B

AU - Couch, Fergus J

AU - Pereira, Lutecia H Mateus

AU - Greene, Mark H

AU - Andrulis, Irene L

AU - Pasche, Boris

AU - Kaklamani, Virginia

AU - Hamann, Ute

AU - Szabo, Csilla

AU - Peock, Susan

AU - Cook, Margaret

AU - Harrington, Patricia A.

AU - Donaldson, A

AU - Male, Allison M

AU - Gardiner, Carol Anne

AU - Gregory, Helen

AU - Side, Lucy E

AU - Robinson, Anne C.

AU - Emmerson, Louise

AU - Ellis, Ian

AU - Peyrat, Jean-Philippe

AU - Fournier, Joëlle

AU - Adenis, Claude

AU - Vennin, Philippe

AU - Muller, Danièle

AU - Fricker, Jean-Pierre

AU - Longy, Michel

AU - Sinilnikova, Olga M

AU - Stoppa-Lyonnet, Dominique

AU - Schmutzler, Rita K

AU - Versmold, Beatrix

AU - Engel, Christoph

AU - Meindl, Alfons

AU - Kast, Karin

AU - Schaefer, Dieter

AU - Froster, Ursula G

AU - Chenevix-Trench, Georgia

AU - Easton, Douglas F

AU - kConFaB

PY - 2009/5

Y1 - 2009/5

N2 - 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.

AB - 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.

KW - adult

KW - alleles

KW - breast neoplasms

KW - cohort studies

KW - female

KW - genes, BRCA1

KW - genes, BRCA2

KW - genetic predisposition to disease

KW - genotype

KW - heterozygote

KW - humans

KW - mutation

KW - risk

KW - transforming growth factor beta

KW - BRCA1

KW - BRCA2

KW - risk modifiers

KW - hereditary cancer

U2 - 10.1007/s10549-008-0064-8

DO - 10.1007/s10549-008-0064-8

M3 - Article

C2 - 18523885

VL - 115

SP - 185

EP - 192

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 1

ER -