Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042.
BACKGROUND
A recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium.


METHODS
2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided.


RESULTS
We found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; P(trend) = 1.0 x 10(-19)). The odds ratio was lower than that previously reported (P = .02) and did not vary by age or ethnicity (all P > or = .2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10(-15)) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P = .0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 x 10(-14)) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P = .00002).


CONCLUSIONS
The rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.
Milne
Roger L
RL
Genetic and Molecular Epidemiology Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 29029 Madrid, Spain. rmilne@cnio.es
Benítez
Javier
J
Nevanlinna
Heli
H
Heikkinen
Tuomas
T
Aittomäki
Kristiina
K
Blomqvist
Carl
C
Arias
José Ignacio
JI
Zamora
M Pilar
MP
Burwinkel
Barbara
B
Bartram
Claus R
CR
Meindl
Alfons
A
Schmutzler
Rita K
RK
Cox
Angela
A
Brock
Ian
I
Elliott
Graeme
G
Reed
Malcolm W R
MW
Southey
Melissa C
MC
Smith
Letitia
L
Spurdle
Amanda B
AB
Hopper
John L
JL
Couch
Fergus J
FJ
Olson
Janet E
JE
Wang
Xianshu
X
Fredericksen
Zachary
Z
Schürmann
Peter
P
Bremer
Michael
M
Hillemanns
Peter
P
Dörk
Thilo
T
Devilee
Peter
P
van Asperen
Christie J
CJ
Tollenaar
Rob A E M
RA
Seynaeve
Caroline
C
Hall
Per
P
Czene
Kamila
K
Liu
Jianjun
J
Li
Yuqing
Y
Ahmed
Shahana
S
Dunning
Alison M
AM
Maranian
Melanie
M
Pharoah
Paul D P
PD
Chenevix-Trench
Georgia
G
Beesley
Jonathan
J
Bogdanova
Natalia V
NV
Antonenkova
Natalia N
NN
Zalutsky
Iosif V
IV
Anton-Culver
Hoda
H
Ziogas
Argyrios
A
Brauch
Hiltrud
H
Justenhoven
Christina
C
Ko
Yon-Dschun
YD
Haas
Susanne
S
Fasching
Peter A
PA
Strick
Reiner
R
Ekici
Arif B
AB
Beckmann
Matthias W
MW
Giles
Graham G
GG
Severi
Gianluca
G
Baglietto
Laura
L
English
Dallas R
DR
Fletcher
Olivia
O
Johnson
Nichola
N
dos Santos Silva
Isabel
I
Peto
Julian
J
Turnbull
Clare
C
Hines
Sarah
S
Renwick
Anthony
A
Rahman
Nazneen
N
Nordestgaard
Børge G
BG
Bojesen
Stig E
SE
Flyger
Henrik
H
Kang
Daehee
D
Yoo
Keun-Young
KY
Noh
Dong-Young
DY
Mannermaa
Arto
A
Kataja
Vesa
V
Kosma
Veli-Matti
VM
García-Closas
Montserrat
M
Chanock
Stephen
S
Lissowska
Jolanta
J
Brinton
Louise A
LA
Chang-Claude
Jenny
J
Wang-Gohrke
Shan
S
Shen
Chen-Yang
CY
Wang
Hui-Chun
HC
Yu
Jyh-Cherng
JC
Chen
Sou-Tong
ST
Bermisheva
Marina
M
Nikolaeva
Tatjana
T
Khusnutdinova
Elza
E
Humphreys
Manjeet K
MK
Morrison
Jonathan
J
Platte
Radka
R
Easton
Douglas F
DF
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000235:genetics; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000737:chemistry / Q000235:genetics; D016022:Case-Control Studies; D016001:Confidence Intervals; D015986:Confounding Factors, Epidemiologic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry* / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000235:genetics; D044465:White People / Q000235:genetics*
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone