Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women
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Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women. / Wang, Xiaoliang; Kapoor, Pooja Middha; Auer, Paul L; Dennis, Joe; Dunning, Alison M; Wang, Qin; Lush, Michael; Michailidou, Kyriaki; Bolla, Manjeet K; Aronson, Kristan J; Murphy, Rachel A; Brooks-Wilson, Angela; Lee, Derrick G; Cordina-Duverger, Emilie; Guénel, Pascal; Truong, Thérèse; Mulot, Claire; Teras, Lauren R; Patel, Alpa V; Dossus, Laure; Kaaks, Rudolf; Hoppe, Reiner; Lo, Wing-Yee; Brüning, Thomas; Hamann, Ute; Czene, Kamila; Gabrielson, Marike; Hall, Per; Eriksson, Mikael; Jung, Audrey; Becher, Heiko; Couch, Fergus J; Larson, Nicole L; Olson, Janet E; Ruddy, Kathryn J; Giles, Graham G; MacInnis, Robert J; Southey, Melissa C; Le Marchand, Loic; Wilkens, Lynne R; Haiman, Christopher A; Olsson, Håkan; Augustinsson, Annelie; Krüger, Ute; Wagner, Philippe; Scott, Christopher; Winham, Stacey J; Vachon, Celine M; Perou, Charles M; Olshan, Andrew F; Troester, Melissa A; Hunter, David J; Eliassen, Heather A; Tamimi, Rulla M; Brantley, Kristen; Andrulis, Irene L; Figueroa, Jonine; Chanock, Stephen J; Ahearn, Thomas U; García-Closas, Montserrat; Evans, Gareth D; Newman, William G; van Veen, Elke M; Howell, Anthony; Wolk, Alicja; Håkansson, Niclas; Anton-Culver, Hoda; Ziogas, Argyrios; Jones, Michael E; Orr, Nick; Schoemaker, Minouk J; Swerdlow, Anthony J; Kitahara, Cari M; Linet, Martha; Prentice, Ross L; Easton, Douglas F; Milne, Roger L; Kraft, Peter; Chang-Claude, Jenny; Lindström, Sara.
In: SCI REP-UK, Vol. 12, No. 1, 6199, 13.04.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women
AU - Wang, Xiaoliang
AU - Kapoor, Pooja Middha
AU - Auer, Paul L
AU - Dennis, Joe
AU - Dunning, Alison M
AU - Wang, Qin
AU - Lush, Michael
AU - Michailidou, Kyriaki
AU - Bolla, Manjeet K
AU - Aronson, Kristan J
AU - Murphy, Rachel A
AU - Brooks-Wilson, Angela
AU - Lee, Derrick G
AU - Cordina-Duverger, Emilie
AU - Guénel, Pascal
AU - Truong, Thérèse
AU - Mulot, Claire
AU - Teras, Lauren R
AU - Patel, Alpa V
AU - Dossus, Laure
AU - Kaaks, Rudolf
AU - Hoppe, Reiner
AU - Lo, Wing-Yee
AU - Brüning, Thomas
AU - Hamann, Ute
AU - Czene, Kamila
AU - Gabrielson, Marike
AU - Hall, Per
AU - Eriksson, Mikael
AU - Jung, Audrey
AU - Becher, Heiko
AU - Couch, Fergus J
AU - Larson, Nicole L
AU - Olson, Janet E
AU - Ruddy, Kathryn J
AU - Giles, Graham G
AU - MacInnis, Robert J
AU - Southey, Melissa C
AU - Le Marchand, Loic
AU - Wilkens, Lynne R
AU - Haiman, Christopher A
AU - Olsson, Håkan
AU - Augustinsson, Annelie
AU - Krüger, Ute
AU - Wagner, Philippe
AU - Scott, Christopher
AU - Winham, Stacey J
AU - Vachon, Celine M
AU - Perou, Charles M
AU - Olshan, Andrew F
AU - Troester, Melissa A
AU - Hunter, David J
AU - Eliassen, Heather A
AU - Tamimi, Rulla M
AU - Brantley, Kristen
AU - Andrulis, Irene L
AU - Figueroa, Jonine
AU - Chanock, Stephen J
AU - Ahearn, Thomas U
AU - García-Closas, Montserrat
AU - Evans, Gareth D
AU - Newman, William G
AU - van Veen, Elke M
AU - Howell, Anthony
AU - Wolk, Alicja
AU - Håkansson, Niclas
AU - Anton-Culver, Hoda
AU - Ziogas, Argyrios
AU - Jones, Michael E
AU - Orr, Nick
AU - Schoemaker, Minouk J
AU - Swerdlow, Anthony J
AU - Kitahara, Cari M
AU - Linet, Martha
AU - Prentice, Ross L
AU - Easton, Douglas F
AU - Milne, Roger L
AU - Kraft, Peter
AU - Chang-Claude, Jenny
AU - Lindström, Sara
N1 - © 2022. The Author(s).
PY - 2022/4/13
Y1 - 2022/4/13
N2 - 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.
AB - 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.
KW - Breast
KW - Breast Neoplasms/chemically induced
KW - Estrogen Replacement Therapy/adverse effects
KW - Female
KW - Hormone Replacement Therapy/adverse effects
KW - Humans
KW - Male
KW - Menopause
KW - Risk Factors
U2 - 10.1038/s41598-022-10121-2
DO - 10.1038/s41598-022-10121-2
M3 - SCORING: Journal article
C2 - 35418701
VL - 12
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
IS - 1
M1 - 6199
ER -