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GWAS Study

Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women.

Wang X, Kapoor PM, Auer PL et al.

35418701 PubMed ID
GWAS Study Type
62370 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

WX
Wang X
KP
Kapoor PM
AP
Auer PL
DJ
Dennis J
DA
Dunning AM
WQ
Wang Q
LM
Lush M
MK
Michailidou K
BM
Bolla MK
AK
Aronson KJ
MR
Murphy RA
BA
Brooks-Wilson A
LD
Lee DG
CE
Cordina-Duverger E
GP
Guénel P
TT
Truong T
MC
Mulot C
TL
Teras LR
PA
Patel AV
DL
Dossus L
KR
Kaaks R
HR
Hoppe R
LW
Lo WY
BT
Brüning T
HU
Hamann U
CK
Czene K
GM
Gabrielson M
HP
Hall P
EM
Eriksson M
JA
Jung A
BH
Becher H
CF
Couch FJ
LN
Larson NL
OJ
Olson JE
RK
Ruddy KJ
GG
Giles GG
MR
MacInnis RJ
SM
Southey MC
LM
Le Marchand L
WL
Wilkens LR
HC
Haiman CA
OH
Olsson H
AA
Augustinsson A
KU
Krüger U
WP
Wagner P
SC
Scott C
WS
Winham SJ
VC
Vachon CM
PC
Perou CM
OA
Olshan AF
TM
Troester MA
HD
Hunter DJ
EH
Eliassen HA
TR
Tamimi RM
BK
Brantley K
AI
Andrulis IL
FJ
Figueroa J
CS
Chanock SJ
AT
Ahearn TU
GM
García-Closas M
EG
Evans GD
NW
Newman WG
VV
van Veen EM
HA
Howell A
WA
Wolk A
HN
Håkansson N
AH
Anton-Culver H
ZA
Ziogas A
JM
Jones ME
ON
Orr N
SM
Schoemaker MJ
SA
Swerdlow AJ
KC
Kitahara CM
LM
Linet M
PR
Prentice RL
ED
Easton DF
MR
Milne RL
KP
Kraft P
CJ
Chang-Claude J
LS
Lindström S
Chapter II

Abstract

Summary of the research findings

Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values < 5 × 10-8 as genome-wide significant, and p-values < 1 × 10-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values < 1 × 105. The strongest evidence was found for rs4674019 (p-value = 2.27 × 10-7), which showed genome-wide significant interaction (p-value = 3.8 × 10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT-breast cancer risk association.

27,585 European ancestry cases, 34,785 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

62370
Total Participants
GWAS
Study Type
No
Replicated
European
Ancestry
Chapter IV

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