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

被引：3

作者：

Wang, Xiaoliang ^{[1
,2
]}

Kapoor, Pooja Middha ^{[3
,4
]}

Auer, Paul L. ^{[5
,6
,7
]}

Dennis, Joe ^{[8
]}

Dunning, Alison M. ^{[9
]}

Wang, Qin ^{[8
]}

Lush, Michael ^{[8
]}

Michailidou, Kyriaki ^{[8
,10
,11
]}

Bolla, Manjeet K. ^{[8
]}

Aronson, Kristan J. ^{[12
]}

Murphy, Rachel A. ^{[13
,14
]}

Brooks-Wilson, Angela ^{[15
,16
]}

Lee, Derrick G. ^{[14
,17
]}

Guenel, Pascal ^{[18
]}

Truong, Therese ^{[18
]}

Mulot, Claire ^{[19
]}

Teras, Lauren R. ^{[20
]}

Patel, Alpa, V ^{[20
]}

Dossus, Laure ^{[21
]}

Kaaks, Rudolf ^{[3
]}

Hoppe, Reiner ^{[22
,23
]}

Bruening, Thomas ^{[24
]}

Hamann, Ute ^{[25
]}

Czene, Kamila ^{[26
]}

Gabrielson, Marike ^{[26
]}

Hall, Per ^{[26
,27
]}

Eriksson, Mikael ^{[26
]}

Jung, Audrey ^{[3
]}

Becher, Heiko ^{[28
]}

Couch, Fergus J. ^{[29
]}

Larson, Nicole L. ^{[30
]}

Olson, Janet E. ^{[30
]}

Ruddy, Kathryn J. ^{[31
]}

Giles, Graham G. ^{[32
,33
,34
]}

MacInnis, Robert J. ^{[32
,33
]}

Southey, Melissa C. ^{[32
,34
,35
]}

Le Marchand, Loic ^{[36
]}

Wilkens, Lynne R. ^{[37
]}

Haiman, Christopher A. ^{[38
]}

Olsson, Hakan ^{[39
]}

Augustinsson, Annelie ^{[39
]}

Krueger, Ute ^{[39
]}

Wagner, Philippe ^{[39
]}

Scott, Christopher ^{[30
]}

Winham, Stacey J. ^{[40
]}

Vachon, Celine M. ^{[41
,42
]}

Perou, Charles M. ^{[41
,42
]}

Olshan, Andrew F. ^{[43
]}

Troester, Melissa A. ^{[43
]}

Hunter, David J. ^{[44
,45
]}

机构：

[1] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA

[2] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, 1124 Columbia St, Seattle, WA 98104 USA

[3] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[4] Heidelberg Univ, Fac Med, Heidelberg, Germany

[5] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA

[6] Med Coll Wisconsin, Inst Hlth & Equ, Div Biostat, Milwaukee, WI 53226 USA

[7] Med Coll Wisconsin, Canc Ctr, Milwaukee, WI 53226 USA

[8] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England

[9] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England

[10] Cyprus Inst Neurol & Genet, Biostat Unit, Nicosia, Cyprus

[11] Cyprus Sch Mol Med, Cyprus Inst Neurol & Genet, Nicosia, Cyprus

[12] Queens Univ, Canc Res Inst, Dept Publ Hlth Sci, Kingston, ON, Canada

[13] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC, Canada

[14] BC Canc, Canc Control Res, Vancouver, BC, Canada

[15] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada

[16] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC, Canada

[17] St Francis Xavier Univ, Dept Math & Stat, Antigonish, NS, Canada

[18] Univ Paris Saclay, Ctr Res Epidemiol & Populat Hlth CESP, INSERM, Team Exposome & Hered, Villejuif, France

[19] Univ Paris Sorbonne, INSERM UMR S1147, Paris, France

[20] Amer Canc Soc, Dept Populat Sci, Atlanta, GA 30329 USA

[21] Int Agcy Res Canc IARC WHO, Nutr & Metab Branch, Lyon, France

[22] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany

[23] Univ Tybingen, Tybingen, Germany

[24] Inst Ruhr Univ Bochum IPA, Inst Prevent & Occupat Med, German Social Accid Insurance, Bochum, Germany

[25] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany

[26] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[27] Soder Sjukhuset, Dept Oncol, Stockholm, Sweden

[28] Univ Med Ctr Hamburg Eppendorf, Inst Med Biometry & Epidemiol, Hamburg, Germany

[29] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[30] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[31] Mayo Clin, Dept Oncol, Rochester, MN USA

[32] Canc Council Victoria, Canc Epidemiol Div, Melbourne, Vic, Australia

[33] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia

[34] Monash Univ, Sch Clin Sci Monash Hlth, Precis Med, Clayton, Vic, Australia

[35] Univ Melbourne, Dept Clin Pathol, Melbourne, Vic, Australia

[36] Univ Hawaii Canc Ctr, Epidemiol Program, Honolulu, HI USA

[37] Univ Hawaii Canc Ctr, Canc Epidemiol Program, Honolulu, HI USA

[38] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA

[39] Lund Univ, Dept Canc Epidemiol, Clin Sci, Lund, Sweden

[40] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA

[41] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA

[42] Univ North Carolina Chapel Hill, Dept Genet, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[43] Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[44] Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England

[45] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[46] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

[47] Weill Cornell Med, Dept Populat Hlth Sci, New York, NY USA

[48] Fred A Litwin Ctr Canc Genet, Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp, Toronto, ON, Canada

[49] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[50] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland

来源：

SCIENTIFIC REPORTS | 2022年 / 12卷 / 01期

基金：

加拿大健康研究院; 瑞典研究理事会; 美国国家卫生研究院; 欧盟地平线“2020”; 英国医学研究理事会;

关键词：

ESTROGEN PLUS PROGESTIN; REPLACEMENT THERAPY; ASSOCIATION ANALYSIS; SUSCEPTIBILITY LOCI; CELLS; METAANALYSIS; PATHWAY; MODIFY; GENE;

D O I：

10.1038/s41598-022-10121-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 x 10(-8) as genome-wide significant, and p-values < 1 x 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 x 10(5). The strongest evidence was found for rs4674019 (p-value = 2.27 x 10(-7)), which showed genome-wide significant interaction (p-value = 3.8 x 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.

引用

页数：12

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