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.
Department of Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. gaudetm@mskcc.org
Mia M
MM
Gaudet
Roger L
RL
Milne
Angela
A
Cox
Nicola J
NJ
Camp
Ellen L
EL
Goode
Manjeet K
MK
Humphreys
Alison M
AM
Dunning
Jonathan
J
Morrison
Graham G
GG
Giles
Gianluca
G
Severi
Laura
L
Baglietto
Dallas R
DR
English
Fergus J
FJ
Couch
Janet E
JE
Olson
Xianshu
X
Wang
Jenny
J
Chang-Claude
Dieter
D
Flesch-Janys
Sascha
S
Abbas
Ramona
R
Salazar
Arto
A
Mannermaa
Vesa
V
Kataja
Veli-Matti
VM
Kosma
Annika
A
Lindblom
Sara
S
Margolin
Tuomas
T
Heikkinen
Kati
K
Kämpjärvi
Kirsimari
K
Aaltonen
Heli
H
Nevanlinna
Natalia
N
Bogdanova
Irina
I
Coinac
Peter
P
Schürmann
Thilo
T
Dörk
Claus R
CR
Bartram
Rita K
RK
Schmutzler
Sandrine
S
Tchatchou
Barbara
B
Burwinkel
Hiltrud
H
Brauch
Diana
D
Torres
Ute
U
Hamann
Christina
C
Justenhoven
Gloria
G
Ribas
José I
JI
Arias
Javier
J
Benitez
Stig E
SE
Bojesen
Børge G
BG
Nordestgaard
Henrik L
HL
Flyger
Julian
J
Peto
Olivia
O
Fletcher
Nichola
N
Johnson
Isabel
I
Dos Santos Silva
Peter A
PA
Fasching
Matthias W
MW
Beckmann
Reiner
R
Strick
Arif B
AB
Ekici
Annegien
A
Broeks
Marjanka K
MK
Schmidt
Flora E
FE
van Leeuwen
Laura J
LJ
Van't Veer
Melissa C
MC
Southey
John L
JL
Hopper
Carmel
C
Apicella
Christopher A
CA
Haiman
Brian E
BE
Henderson
Loic
L
Le Marchand
Laurence N
LN
Kolonel
Vessela
V
Kristensen
Grethe
G
Grenaker Alnaes
David J
DJ
Hunter
Peter
P
Kraft
David G
DG
Cox
Susan E
SE
Hankinson
Caroline
C
Seynaeve
Maaike P G
MP
Vreeswijk
Rob A E M
RA
Tollenaar
Peter
P
Devilee
Stephen
S
Chanock
Jolanta
J
Lissowska
Louise
L
Brinton
Beata
B
Peplonska
Kamila
K
Czene
Per
P
Hall
Yuqing
Y
Li
Jianjun
J
Liu
Sabapathy
S
Balasubramanian
Saeed
S
Rafii
Malcolm W R
MW
Reed
Karen A
KA
Pooley
Don
D
Conroy
Caroline
C
Baynes
Daehee
D
Kang
Keun-Young
KY
Yoo
Dong-Young
DY
Noh
Sei-Hyun
SH
Ahn
Chen-Yang
CY
Shen
Hui-Chun
HC
Wang
Jyh-Cherng
JC
Yu
Pei-Ei
PE
Wu
Hoda
H
Anton-Culver
Argyrios
A
Ziogoas
Kathleen
K
Egan
Polly
P
Newcomb
Linda
L
Titus-Ernstoff
Amy
A
Trentham Dietz
Alice J
AJ
Sigurdson
Bruce H
BH
Alexander
Parveen
P
Bhatti
Kristina
K
Allen-Brady
Lisa A
LA
Cannon-Albright
Jathine
J
Wong
Georgia
G
Chenevix-Trench
Amanda B
AB
Spurdle
Jonathan
J
Beesley
Paul D P
PD
Pharoah
Doug F
DF
Easton
Montserrat
M
Garcia-Closas
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