Joint associations of a polygenic risk score and environmental risk factors for breast cancer in the Breast Cancer Association Consortium

被引：70

作者：

Rudolph, Anja ^{[1
,2
]}

Song, Minsun ^{[3
]}

Brook, Mark N. ^{[4
]}

Milne, Roger L. ^{[5
,6
]}

Mavaddat, Nasim ^{[7
]}

Michailidou, Kyriaki ^{[7
,8
]}

Bolla, Manjeet K. ^{[7
]}

Wang, Qin ^{[7
]}

Dennis, Joe ^{[7
]}

Wilcox, Amber N. ^{[9
]}

Hopper, John L. ^{[6
]}

Southey, Melissa C. ^{[10
]}

Keeman, Renske ^{[11
]}

Fasching, Peter A. ^{[12
,13
]}

Beckmann, Matthias W. ^{[12
]}

Gago-Dominguez, Manuela ^{[14
,15
]}

Castelao, Jose E. ^{[16
]}

Guenel, Pascal ^{[17
]}

Truong, Therese ^{[17
]}

Bojesen, Stig E. ^{[18
,19
,20
]}

Flyger, Henrik ^{[21
]}

Brenner, Hermann ^{[22
,23
,24
]}

Arndt, Volker ^{[22
]}

Brauch, Hiltrud ^{[24
,25
,26
]}

Bruening, Thomas ^{[27
]}

Mannermaa, Arto ^{[28
,29
,30
]}

Kosma, Veli-Matti ^{[31
,32
]}

Lambrechts, Diether ^{[33
]}

Keupers, Machteld ^{[34
]}

Couch, Fergus J. ^{[35
]}

Vachon, Celine ^{[5
,6
]}

Giles, Graham G. ^{[5
,6
]}

MacInnis, Robert J. ^{[5
,6
]}

Figueroa, Jonine ^{[9
,36
]}

Brinton, Louise ^{[9
]}

Czene, Kamila ^{[37
]}

Brand, Judith S. ^{[37
]}

Gabrielson, Marike ^{[37
]}

Humphreys, Keith ^{[37
]}

Cox, Angela ^{[38
]}

Cross, Simon S. ^{[39
]}

Dunning, Alison M. ^{[40
]}

Orr, Nick ^{[41
]}

Swerdlow, Anthony ^{[41
]}

Hall, Per ^{[37
]}

Pharoah, Paul D. P. ^{[40
]}

Schmidt, Marjanka K. ^{[11
,42
]}

Easton, Douglas F. ^{[40
]}

Chatterjee, Nilanjan ^{[9
,43
,44
]}

Chang-Claude, Jenny ^{[1
,45
]}

机构：

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

[2] QuintilesIMS, Real World Insights, CESE, Frankfurt, Germany

[3] Sookmyung Womens Univ, Dept Stat, Seoul, South Korea

[4] Inst Canc Res, Div Genet & Epidemiol, London, England

[5] Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia

[6] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia

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

[8] Cyprus Inst Neurol & Genet, Dept Elect Microscopy Mol Pathol, Nicosia, Cyprus

[9] NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,MSC 9776, Bethesda, MD 20892 USA

[10] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia

[11] Netherlands Canc Inst, Antoni van Leeuwenhoek Hosp, Div Mol Pathol, Amsterdam, Netherlands

[12] Friedrich Alexander Univ Erlangen Nuremberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Dept Gynaecol & Obstet, Erlangen, Germany

[13] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA

[14] Complejo Hosp Univ Santiago, Inst Invest Sanitaria Santiago, Genom Med Grp, IDIS,Galician Fdn Genom Med, Santiago De Compostela, Spain

[15] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

[16] Complejo Hosp Univ Vigo, Inst Investigac Sanitaria Galicia, Oncol & Genet Unit, Vigo, Spain

[17] Univ Paris Sud, Univ Paris Saclay, Ctr Res Epidemiol & Populat Hlth, Villejuif, France

[18] Copenhagen Gen Populat Study, Copenhagen, Denmark

[19] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark

[20] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark

[21] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Breast Surg, Herlev, Denmark

[22] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[23] German Canc Res Ctr, Div Prevent Oncol, Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[24] German Canc Res Ctr, German Canc Consortium, Heidelberg, Germany

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

[26] Univ Tubingen, Dept Clin Pharmacol, Tubingen, Germany

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

[28] Univ Eastern Finland, Translat Canc Res Area, Kuopio, Finland

[29] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio, Finland

[30] Kuopio Univ Hosp, Dept Clin Pathol, Kuopio, Finland

[31] VIB Ctr Canc Biol, Leuven, Belgium

[32] Univ Leuven, Lab Translat Genet, Leuven, Belgium

[33] Univ Hosp Leuven, Dept Radiat Oncol, Leuven, Belgium

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

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

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

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

[38] Univ Sheffield, Dept Oncol & Metab, Sheffield, S Yorkshire, England

[39] Univ Sheffield, Dept Neurosci, Sheffield, S Yorkshire, England

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

[41] Inst Canc Res, Div Breast Canc Res, London, England

[42] Netherlands Canc Inst, Antoni van Leeuwenhoek Hosp, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands

[43] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA

[44] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA

[45] Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg, Hamburg, Germany

来源：

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY | 2018年 / 47卷 / 02期

关键词：

Breast cancer; genetic susceptibility; gene-environment interactions; risk prediction; epidemiology; SUSCEPTIBILITY LOCI; TUMOR SUBTYPES; PREDICTION; MODELS;

D O I：

10.1093/ije/dyx242

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

Background: Polygenic risk scores (PRS) for breast cancer can be used to stratify the population into groups at substantially different levels of risk. Combining PRS and environmental risk factors will improve risk prediction; however, integrating PRS into risk prediction models requires evaluation of their joint association with known environmental risk factors. Methods: Analyses were based on data from 20 studies; datasets analysed ranged from 3453 to 23 104 invasive breast cancer cases and similar numbers of controls, depending on the analysed environmental risk factor. We evaluated joint associations of a 77-single nucleotide polymorphism (SNP) PRS with reproductive history, alcohol consumption, menopausal hormone therapy (MHT), height and body mass index (BMI). We tested the null hypothesis of multiplicative joint associations for PRS and each of the environmental factors, and performed global and tail-based goodness-of-fit tests in logistic regression models. The outcomes were breast cancer overall and by estrogen receptor (ER) status. Results: The strongest evidence for a non-multiplicative joint associations with the 77-SNP PRS was for alcohol consumption (P-interaction = 0.009), adult height (P-interaction = 0.025) and current use of combined MHT (P-interaction = 0.038) in ER-positive disease. Risk associations for these factors by percentiles of PRS did not follow a clear dose-response. In addition, global and tail-based goodness of fit tests showed little evidence for departures from a multiplicative risk model, with alcohol consumption showing the strongest evidence for ER-positive disease (P = 0.013 for global and 0.18 for tail-based tests). Conclusions: The combined effects of the 77-SNP PRS and environmental risk factors for breast cancer are generally well described by a multiplicative model. Larger studies are required to confirm possible departures from the multiplicative model for individual risk factors, and assess models specific for ER-negative disease.

引用

页码：526 / 536

页数：11

共 25 条

[1] Post-G WAS gene-environment interplay in breast cancer: results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79 000 women
Barrdahl, Myrto
Canzian, Federico
Joshi, Amit D.
Travis, Ruth C.
Chang-Claude, Jenny
Auer, Paul L.
Gapstur, Susan M.
Gaudet, Mia
Diver, W. Ryan
Henderson, Brian E.
Haiman, Christopher A.
Schumacher, Fredrick R.
Le Marchand, Loic
Berg, Christine D.
Chanock, Stephen J.
Hoover, Robert N.
Rudolph, Anja
Ziegler, Regina G.
Giles, Graham G.
Baglietto, Laura
Severi, Gianluca
Hankinson, Susan E.
Lindstroem, Sara
Willet, Walter
Hunter, David J.
Buring, Julie E.
Lee, I-Min
Zhang, Shumin
Dossus, Laure
Cox, David G.
Khaw, Kay-Tee
Lund, Eiliv
Naccarati, Alessio
Peeters, Petra H.
Ramon Quiros, J.
Riboli, Elio
Sund, Malin
Trichopoulos, Dimitrios
Prentice, Ross L.
Kraft, Peter
Kaaks, Rudolf
Campa, Daniele
[J]. HUMAN MOLECULAR GENETICS, 2014, 23 (19) : 5260 - 5270
[2] Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium
Broeks, Annegien
Schmidt, Marjanka K.
Sherman, Mark E.
Couch, Fergus J.
Hopper, John L.
Dite, Gillian S.
Apicella, Carmel
Smith, Letitia D.
Hammet, Fleur
Southey, Melissa C.
Van 't Veer, Laura J.
de Groot, Renate
Smit, Vincent T. H. B. M.
Fasching, Peter A.
Beckmann, Matthias W.
Jud, Sebastian
Ekici, Arif B.
Hartmann, Arndt
Hein, Alexander
Schulz-Wendtland, Ruediger
Burwinkel, Barbara
Marme, Frederik
Schneeweiss, Andreas
Sinn, Hans-Peter
Sohn, Christof
Tchatchou, Sandrine
Bojesen, Stig E.
Nordestgaard, Borge G.
Flyger, Henrik
Orsted, David D.
Kaur-Knudsen, Diljit
Milne, Roger L.
Perez, Jose I. Arias
Zamora, Pilar
Menendez Rodriguez, Primitiva
Benitez, Javier
Brauch, Hiltrud
Justenhoven, Christina
Ko, Yon-Dschun
Hamann, Ute
Fischer, Hans-Peter
Bruening, Thomas
Pesch, Beate
Chang-Claude, Jenny
Wang-Gohrke, Shan
Bremer, Michael
Karstens, Johann H.
Hillemanns, Peter
Doerk, Thilo
Nevanlinna, Heli A.
[J]. HUMAN MOLECULAR GENETICS, 2011, 20 (16) : 3289 - 3303
[3] Public health implications from COGS and potential for risk stratification and screening
Burton, Hilary
Chowdhury, Susmita
Dent, Tom
Hall, Alison
Pashayan, Nora
Pharoah, Paul
[J]. NATURE GENETICS, 2013, 45 (04) : 349 - 351
[4] Interactions Between Genetic Variants and Breast Cancer Risk Factors in the Breast and Prostate Cancer Cohort Consortium
Campa, Daniele
Kaaks, Rudolf
Le Marchand, Loic
Haiman, Christopher A.
Travis, Ruth C.
Berg, Christine D.
Buring, Julie E.
Chanock, Stephen J.
Diver, W. Ryan
Dostal, Lucie
Fournier, Agnes
Hankinson, Susan E.
Henderson, Brian E.
Hoover, Robert N.
Isaacs, Claudine
Johansson, Mattias
Kolonel, Laurence N.
Kraft, Peter
Lee, I-Min
McCarty, Catherine A.
Overvad, Kim
Panico, Salvatore
Peeters, Petra H. M.
Riboli, Elio
Jose Sanchez, Maria
Schumacher, Fredrick R.
Skeie, Guri
Stram, Daniel O.
Thun, Michael J.
Trichopoulos, Dimitrios
Zhang, Shumin
Ziegler, Regina G.
Hunter, David J.
Lindstroem, Sara
Canzian, Federico
[J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2011, 103 (16): : 1252 - 1263
[5] Developing and evaluating polygenic risk prediction models for stratified disease prevention
Chatterjee, Nilanjan
Shi, Jianxin
Garcia-Closas, Montserrat
[J]. NATURE REVIEWS GENETICS, 2016, 17 (07) : 392 - 406
[6] Colditz GA., 2006, Cancer epidemiology and prevention, V3rd
[7] García-Closas M, 1998, AM J EPIDEMIOL, V147, P426
[8] Combined Associations of Genetic and Environmental Risk Factors: Implications for Prevention of Breast Cancer
Garcia-Closas, Montserrat
Gunsoy, Necdet Burak
Chatterjee, Nilanjan
[J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2014, 106 (11):
[9] Genome-wide association studies identify four ER negative-specific breast cancer risk loci
Garcia-Closas, Montserrat
Couch, Fergus J.
Lindstrom, Sara
Michailidouo, Kyriaki
Schmidt, Marjanka K.
Brook, Mark N.
Orr, Nick
Rhie, Suhn Kyong
Riboli, Elio
Feigelson, Heather S.
Le Marchand, Loic
Buring, Julie E.
Eccles, Diana
Miron, Penelope
Fasching, Peter A.
Brauch, Hiltrud
Chang-Claude, Jenny
Carpenter, Jane
Godwin, Andrew K.
Nevanlinna, Heli
Giles, Graham G.
Cox, Angela
Hopper, John L.
Bolla, Manjeet K.
Wang, Qin
Dennis, Joe
Dicks, Ed
Howat, Will J.
Schoof, Nils
Bojesen, Stig E.
Lambrechts, Diether
Broeks, Annegien
Andrulis, Irene L.
Guenel, Pascal
Burwinkel, Barbara
Sawyer, Elinor J.
Hollestelle, Antoinette
Fletcher, Olivia
Winqvist, Robert
Brenner, Hermann
Mannermaa, Arto
Hamann, Ute
Meindl, Alfons
Lindblom, Annika
Zheng, Wei
Devillee, Peter
Goldberg, Mark S.
Lubinski, Jan
Kristensen, Vessela
Swerdlow, Anthony
[J]. NATURE GENETICS, 2013, 45 (04) : 392 - 398
[10] Genetic Susceptibility Loci for Breast Cancer by Estrogen Receptor Status
Garcia-Closas, Montserrat
Chanock, Stephen
[J]. CLINICAL CANCER RESEARCH, 2008, 14 (24) : 8000 - 8009

← 1 2 3 →