A common coding variant in CASP8 is associated with breast cancer risk.
The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.
Cox
Angela
A
Sheffield University Medical School, Sheffield S10 2RX, UK.
Dunning
Alison M
AM
Garcia-Closas
Montserrat
M
Balasubramanian
Sabapathy
S
Reed
Malcolm W R
MW
Pooley
Karen A
KA
Scollen
Serena
S
Baynes
Caroline
C
Ponder
Bruce A J
BA
Chanock
Stephen
S
Lissowska
Jolanta
J
Brinton
Louise
L
Peplonska
Beata
B
Southey
Melissa C
MC
Hopper
John L
JL
McCredie
Margaret R E
MR
Giles
Graham G
GG
Fletcher
Olivia
O
Johnson
Nichola
N
dos Santos Silva
Isabel
I
Gibson
Lorna
L
Bojesen
Stig E
SE
Nordestgaard
Børge G
BG
Axelsson
Christen K
CK
Torres
Diana
D
Hamann
Ute
U
Justenhoven
Christina
C
Brauch
Hiltrud
H
Chang-Claude
Jenny
J
Kropp
Silke
S
Risch
Angela
A
Wang-Gohrke
Shan
S
Schürmann
Peter
P
Bogdanova
Natalia
N
Dörk
Thilo
T
Fagerholm
Rainer
R
Aaltonen
Kirsimari
K
Blomqvist
Carl
C
Nevanlinna
Heli
H
Seal
Sheila
S
Renwick
Anthony
A
Stratton
Michael R
MR
Rahman
Nazneen
N
Sangrajrang
Suleeporn
S
Hughes
David
D
Odefrey
Fabrice
F
Brennan
Paul
P
Spurdle
Amanda B
AB
Chenevix-Trench
Georgia
G
Beesley
Jonathan
J
Mannermaa
Arto
A
Hartikainen
Jaana
J
Kataja
Vesa
V
Kosma
Veli-Matti
VM
Couch
Fergus J
FJ
Olson
Janet E
JE
Goode
Ellen L
EL
Broeks
Annegien
A
Schmidt
Marjanka K
MK
Hogervorst
Frans B L
FB
Van't Veer
Laura J
LJ
Kang
Daehee
D
Yoo
Keun-Young
KY
Noh
Dong-Young
DY
Ahn
Sei-Hyun
SH
Wedrén
Sara
S
Hall
Per
P
Low
Yen-Ling
YL
Liu
Jianjun
J
Milne
Roger L
RL
Ribas
Gloria
G
Gonzalez-Neira
Anna
A
Benitez
Javier
J
Sigurdson
Alice J
AJ
Stredrick
Denise L
DL
Alexander
Bruce H
BH
Struewing
Jeffery P
JP
Pharoah
Paul D P
PD
Easton
Douglas F
DF
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C505530:CASP8 protein, human; D053181:Caspase 8