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 Male; Carol 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

doi:10.1007/s10549-008-0064-8

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

School of Medicine, Medical Sciences & Nutrition

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	185-192
Number of pages	8
Journal	Breast Cancer Research and Treatment
Volume	115
Issue number	1
Early online date	4 Jun 2008
DOIs	https://doi.org/10.1007/s10549-008-0064-8
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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

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

@article{86651f5505e9466b9ffdebdd87de0144,

title = "No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a multi-center cohort study",

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.",

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 ",

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

year = "2009",

month = may,

doi = "10.1007/s10549-008-0064-8",

language = "English",

volume = "115",

pages = "185--192",

journal = "Breast Cancer Research and Treatment",

issn = "0167-6806",

publisher = "Springer New York",

number = "1",

}

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

SN - 0167-6806

VL - 115

SP - 185

EP - 192

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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