Gene-environment interactions involving functional variants: Results from the Breast Cancer Association Consortium

被引：21

作者：

Barrdahl, Myrto ^{[1
]}

Rudolph, Anja ^{[1
]}

Hopper, John L. ^{[2
]}

Southey, Melissa C. ^{[3
]}

Broeks, Annegien ^{[4
]}

Fasching, Peter A. ^{[5
,6
]}

Beckmann, Matthias W. ^{[5
]}

Gago-Dominguez, Manuela ^{[7
,8
]}

Castelao, J. Esteban ^{[9
]}

Guenel, Pascal ^{[10
]}

Truong, Therese ^{[10
]}

Bojesen, Stig E. ^{[11
,12
,13
]}

Gapstur, Susan M. ^{[14
]}

Gaudet, Mia M. ^{[14
]}

Brenner, Hermann ^{[15
,16
,17
,18
]}

Arndt, Volker ^{[15
]}

Brauch, Hiltrud ^{[18
,19
,20
]}

Hamann, Ute ^{[21
]}

Mannermaa, Arto ^{[22
,23
,24
]}

Lambrechts, Diether ^{[25
,26
]}

Jongen, Lynn ^{[27
,28
]}

Flesch-Janys, Dieter ^{[29
,30
]}

Thoene, Kathrin ^{[30
]}

Couch, Fergus J. ^{[31
]}

Giles, Graham G. ^{[2
,32
]}

Simard, Jacques ^{[33
]}

Goldberg, Mark S. ^{[34
,35
]}

Figueroa, Jonine ^{[36
,37
]}

Michailidou, Kyriaki ^{[38
,39
]}

Bolla, Manjeet K. ^{[38
]}

Dennis, Joe ^{[38
]}

Wang, Qin ^{[38
]}

Eilber, Ursula ^{[1
]}

Behrens, Sabine ^{[1
]}

Czene, Kamila ^{[40
]}

Hall, Per ^{[40
]}

Cox, Angela ^{[41
]}

Cross, Simon ^{[42
]}

Swerdlow, Anthony ^{[43
]}

Schoemaker, Minouk J. ^{[44
]}

Dunning, Alison M. ^{[45
]}

Kaaks, Rudolf ^{[1
]}

Pharoah, Paul D. P. ^{[38
,45
]}

Schmidt, Marjanka ^{[4
,46
]}

Garcia-Closas, Montserrat ^{[37
]}

Easton, Douglas F. ^{[38
,45
]}

Milne, Roger L. ^{[2
,32
]}

Chang-Claude, Jenny ^{[1
,47
]}

机构：

[1] Gelman Canc Res Ctr DKFZ, Div Canc Epidemiol, Heidelberg, Germany

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

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

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

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

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

[7] Complejo Hosp Univ Santiago, Inst Invest Sanitaria Santiago de Compostela IDIS, Galician Fdn Genom Med, Genom Med Grp,Serv Galego Saude,SERGAS, Santiago De Compostela, Spain

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

[9] Xerencia Xest Integrada Vigo SERGAS, IISGS, Oncol & Genet Unit, Vigo, Spain

[10] Univ Paris Saclay, Univ Paris Sud, CESP Canc & Environm Team, INSERM U1018, Villejuif, France

[11] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Herlev, Denmark

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

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

[14] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

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

[16] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany

[17] Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[18] German Canc Consortium DKTK, Heidelberg, Germany

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

[20] Univ Tubingen, Tubingen, Germany

[21] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany

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

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

[24] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, Kuopio, Finland

[25] VIB, Vesalius Res Ctr, Leuven, Belgium

[26] Univ Leuven, Dept Human Genet, Lab Translat Genet, Leuven, Belgium

[27] Katholieke Univ Leuven, Dept Oncol, Leuven Multidisciplinary Breast Ctr, Leuven, Belgium

[28] Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium

[29] Univ Med Ctr Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany

[30] Univ Med Ctr Hamburg Eppendorf, UCCH, Dept Canc Epidemiol, Hamburg, Germany

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

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

[33] Laval Univ, Res Ctr, Ctr Hosp Univ Quebec, Genom Ctr, Quebec City, PQ, Canada

[34] McGill Univ, Dept Med, Montreal, PQ, Canada

[35] McGill Univ, Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ, Canada

[36] Univ Edinburgh, Sch Med, Usher Inst Populat Hlth Sci & Informat, Teviot Pl, Edinburgh, Midlothian, Scotland

[37] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

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

[39] Cyprus Inst Neurol & Genet, Dept Electron Microscopy Mol Pathol, Nicosia, Cyprus

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

[41] Univ Sheffield, Dept Oncol & Metab, Sheffield Inst Nucl Acids SInFoNiA, Sheffield, S Yorkshire, England

[42] Univ Sheffield, Dept Neurosci, Acad Unit Pahol, Sheffield, S Yorkshire, England

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

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

[45] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Worts Causeway, Cambridge, England

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

[47] Univ Med Ctr Hamburg Eppendorf, UCCH, Res Grp Genet Canc Epidemiol, Hamburg, Germany

来源：

INTERNATIONAL JOURNAL OF CANCER | 2017年 / 141卷 / 09期

基金：

加拿大健康研究院; 英国医学研究理事会; 澳大利亚国家健康与医学研究理事会; 瑞典研究理事会; 美国国家卫生研究院;

关键词：

breast cancer; single nucleotide polymorphism; Breast Cancer Association Consortium; gene-environment; interaction; INDEPENDENT RISK VARIANTS; SUSCEPTIBILITY LOCI; COHORT CONSORTIUM; WOMEN; EXPRESSION; PHENOTYPE; ENHANCERS; AUTOPHAGY; SUBTYPE;

D O I：

10.1002/ijc.30859

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Investigating the most likely causal variants identified by fine-mapping analyses may improve the power to detect gene-environment interactions. We assessed the interplay between 70 single nucleotide polymorphisms identified by genetic fine-scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor (ER) positive (ER+) and ER negative (ER-) disease. The Bayesian False Discovery Probability (BFDP) was computed to assess the noteworthiness of the results. Four potential gene-environment interactions were identified as noteworthy (BFDP<0.80) when assuming a true prior interaction probability of 0.01. The strongest interaction result in relation to overall breast cancer risk was found between CFLAR-rs7558475 and current smoking (ORint = 0.77, 95% CI: 0.67-0.88, p(int) = 1.8 x 10(-4)). The interaction with the strongest statistical evidence was found between 5q14-rs7707921 and alcohol consumption (ORint = 1.36, 95% CI: 1.16-1.59, Pint = 1.9 x 10(-5)) in relation to ER- disease risk. The remaining two gene-environment interactions were also identified in relation to ER- breast cancer risk and were found between 3p21-rs6796502 and age at menarche (ORint = 1.26, 95% CI: 1.12-1.43, p(int) = 1.8 x 10-4) and between 8q23-rs13267382 and age at first full-term pregnancy (ORint = 0.89, 95% CI: 0.83-0.95, p(int) = 5.2 x 10(-4)). While these results do not suggest any strong gene-environment interactions, our results may still be useful to inform experimental studies. These may in turn, shed light on the potential interactions observed.

引用

页码：1830 / 1840

页数：11

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