No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a multi-center cohort study.
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.
Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. rebbeck@mail.med.upenn.edu
Timothy R
TR
Rebbeck
Antonis C
AC
Antoniou
Trinidad Caldes
TC
Llopis
Heli
H
Nevanlinna
Kristiina
K
Aittomäki
Jacques
J
Simard
Amanda B
AB
Spurdle
Fergus J
FJ
Couch
Lutecia H Mateus
LH
Pereira
Mark H
MH
Greene
Irene L
IL
Andrulis
Boris
B
Pasche
Virginia
V
Kaklamani
Ute
U
Hamann
Csilla
C
Szabo
Susan
S
Peock
Margaret
M
Cook
Patricia A
PA
Harrington
Alan
A
Donaldson
Allison M
AM
Male
Carol Anne
CA
Gardiner
Helen
H
Gregory
Lucy E
LE
Side
Anne C
AC
Robinson
Louise
L
Emmerson
Ian
I
Ellis
Jean-Philippe
JP
Peyrat
Joëlle
J
Fournier
Philippe
P
Vennin
Claude
C
Adenis
Danièle
D
Muller
Jean-Pierre
JP
Fricker
Michel
M
Longy
Olga M
OM
Sinilnikova
Dominique
D
Stoppa-Lyonnet
Rita K
RK
Schmutzler
Beatrix
B
Versmold
Christoph
C
Engel
Alfons
A
Meindl
Karin
K
Kast
Dieter
D
Schaefer
Ursula G
UG
Froster
Georgia
G
Chenevix-Trench
Douglas F
DF
Easton
D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D012306:Risk; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology*
D016212:Transforming Growth Factor beta