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.
Rebbeck
Timothy R
TR
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
Antoniou
Antonis C
AC
Llopis
Trinidad Caldes
TC
Nevanlinna
Heli
H
Aittomäki
Kristiina
K
Simard
Jacques
J
Spurdle
Amanda B
AB
Couch
Fergus J
FJ
Pereira
Lutecia H Mateus
LH
Greene
Mark H
MH
Andrulis
Irene L
IL
Pasche
Boris
B
Kaklamani
Virginia
V
Hamann
Ute
U
Szabo
Csilla
C
Peock
Susan
S
Cook
Margaret
M
Harrington
Patricia A
PA
Donaldson
Alan
A
Male
Allison M
AM
Gardiner
Carol Anne
CA
Gregory
Helen
H
Side
Lucy E
LE
Robinson
Anne C
AC
Emmerson
Louise
L
Ellis
Ian
I
Peyrat
Jean-Philippe
JP
Fournier
Joëlle
J
Vennin
Philippe
P
Adenis
Claude
C
Muller
Danièle
D
Fricker
Jean-Pierre
JP
Longy
Michel
M
Sinilnikova
Olga M
OM
Stoppa-Lyonnet
Dominique
D
Schmutzler
Rita K
RK
Versmold
Beatrix
B
Engel
Christoph
C
Meindl
Alfons
A
Kast
Karin
K
Schaefer
Dieter
D
Froster
Ursula G
UG
Chenevix-Trench
Georgia
G
Easton
Douglas F
DF
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