Five polymorphisms and breast cancer risk: results from the Breast Cancer Association Consortium.
Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent.
Gaudet
Mia M
MM
Department of Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. gaudetm@mskcc.org
Milne
Roger L
RL
Cox
Angela
A
Camp
Nicola J
NJ
Goode
Ellen L
EL
Humphreys
Manjeet K
MK
Dunning
Alison M
AM
Morrison
Jonathan
J
Giles
Graham G
GG
Severi
Gianluca
G
Baglietto
Laura
L
English
Dallas R
DR
Couch
Fergus J
FJ
Olson
Janet E
JE
Wang
Xianshu
X
Chang-Claude
Jenny
J
Flesch-Janys
Dieter
D
Abbas
Sascha
S
Salazar
Ramona
R
Mannermaa
Arto
A
Kataja
Vesa
V
Kosma
Veli-Matti
VM
Lindblom
Annika
A
Margolin
Sara
S
Heikkinen
Tuomas
T
Kämpjärvi
Kati
K
Aaltonen
Kirsimari
K
Nevanlinna
Heli
H
Bogdanova
Natalia
N
Coinac
Irina
I
Schürmann
Peter
P
Dörk
Thilo
T
Bartram
Claus R
CR
Schmutzler
Rita K
RK
Tchatchou
Sandrine
S
Burwinkel
Barbara
B
Brauch
Hiltrud
H
Torres
Diana
D
Hamann
Ute
U
Justenhoven
Christina
C
Ribas
Gloria
G
Arias
José I
JI
Benitez
Javier
J
Bojesen
Stig E
SE
Nordestgaard
Børge G
BG
Flyger
Henrik L
HL
Peto
Julian
J
Fletcher
Olivia
O
Johnson
Nichola
N
Dos Santos Silva
Isabel
I
Fasching
Peter A
PA
Beckmann
Matthias W
MW
Strick
Reiner
R
Ekici
Arif B
AB
Broeks
Annegien
A
Schmidt
Marjanka K
MK
van Leeuwen
Flora E
FE
Van't Veer
Laura J
LJ
Southey
Melissa C
MC
Hopper
John L
JL
Apicella
Carmel
C
Haiman
Christopher A
CA
Henderson
Brian E
BE
Le Marchand
Loic
L
Kolonel
Laurence N
LN
Kristensen
Vessela
V
Grenaker Alnaes
Grethe
G
Hunter
David J
DJ
Kraft
Peter
P
Cox
David G
DG
Hankinson
Susan E
SE
Seynaeve
Caroline
C
Vreeswijk
Maaike P G
MP
Tollenaar
Rob A E M
RA
Devilee
Peter
P
Chanock
Stephen
S
Lissowska
Jolanta
J
Brinton
Louise
L
Peplonska
Beata
B
Czene
Kamila
K
Hall
Per
P
Li
Yuqing
Y
Liu
Jianjun
J
Balasubramanian
Sabapathy
S
Rafii
Saeed
S
Reed
Malcolm W R
MW
Pooley
Karen A
KA
Conroy
Don
D
Baynes
Caroline
C
Kang
Daehee
D
Yoo
Keun-Young
KY
Noh
Dong-Young
DY
Ahn
Sei-Hyun
SH
Shen
Chen-Yang
CY
Wang
Hui-Chun
HC
Yu
Jyh-Cherng
JC
Wu
Pei-Ei
PE
Anton-Culver
Hoda
H
Ziogoas
Argyrios
A
Egan
Kathleen
K
Newcomb
Polly
P
Titus-Ernstoff
Linda
L
Trentham Dietz
Amy
A
Sigurdson
Alice J
AJ
Alexander
Bruce H
BH
Bhatti
Parveen
P
Allen-Brady
Kristina
K
Cannon-Albright
Lisa A
LA
Wong
Jathine
J
Chenevix-Trench
Georgia
G
Spurdle
Amanda B
AB
Beesley
Jonathan
J
Pharoah
Paul D P
PD
Easton
Doug F
DF
Garcia-Closas
Montserrat
M
D000483:Alleles; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D053455:Caspase 10 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D016015:Logistic Models; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C439067:MRFAP1 protein, human; D009687:Nuclear Proteins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C095888:xeroderma pigmentosum group F protein; D053455:Caspase 10; C506438:CASP10 protein, human