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000132915 1001_ $$0P:(DE-He78)3c7f9136fb168ffb766316ea4ca1a58b$$aRudolph, Anja$$b0$$eFirst author
000132915 245__ $$aJoint associations of a polygenic risk score and environmental risk factors for breast cancer in the Breast Cancer Association Consortium.
000132915 260__ $$aOxford$$bOxford Univ. Press$$c2018
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000132915 520__ $$aPolygenic 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.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.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).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.
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000132915 7001_ $$aSong, Minsun$$b1
000132915 7001_ $$aBrook, Mark N$$b2
000132915 7001_ $$aMilne, Roger L$$b3
000132915 7001_ $$aMavaddat, Nasim$$b4
000132915 7001_ $$aMichailidou, Kyriaki$$b5
000132915 7001_ $$aBolla, Manjeet K$$b6
000132915 7001_ $$aWang, Qin$$b7
000132915 7001_ $$aDennis, Joe$$b8
000132915 7001_ $$aWilcox, Amber N$$b9
000132915 7001_ $$aHopper, John L$$b10
000132915 7001_ $$aSouthey, Melissa C$$b11
000132915 7001_ $$aKeeman, Renske$$b12
000132915 7001_ $$aFasching, Peter A$$b13
000132915 7001_ $$aBeckmann, Matthias W$$b14
000132915 7001_ $$aGago-Dominguez, Manuela$$b15
000132915 7001_ $$aCastelao, Jose E$$b16
000132915 7001_ $$aGuénel, Pascal$$b17
000132915 7001_ $$aTruong, Thérèse$$b18
000132915 7001_ $$aBojesen, Stig E$$b19
000132915 7001_ $$aFlyger, Henrik$$b20
000132915 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b21
000132915 7001_ $$0P:(DE-He78)d023fdf423d87ee6c710e34dd7581fa0$$aArndt, Volker$$b22
000132915 7001_ $$0P:(DE-HGF)0$$aBrauch, Hiltrud$$b23
000132915 7001_ $$aBrüning, Thomas$$b24
000132915 7001_ $$aMannermaa, Arto$$b25
000132915 7001_ $$aKosma, Veli-Matti$$b26
000132915 7001_ $$aLambrechts, Diether$$b27
000132915 7001_ $$aKeupers, Machteld$$b28
000132915 7001_ $$aCouch, Fergus J$$b29
000132915 7001_ $$aVachon, Celine$$b30
000132915 7001_ $$aGiles, Graham G$$b31
000132915 7001_ $$aMacInnis, Robert J$$b32
000132915 7001_ $$aFigueroa, Jonine$$b33
000132915 7001_ $$aBrinton, Louise$$b34
000132915 7001_ $$aCzene, Kamila$$b35
000132915 7001_ $$aBrand, Judith S$$b36
000132915 7001_ $$aGabrielson, Marike$$b37
000132915 7001_ $$aHumphreys, Keith$$b38
000132915 7001_ $$aCox, Angela$$b39
000132915 7001_ $$aCross, Simon S$$b40
000132915 7001_ $$aDunning, Alison M$$b41
000132915 7001_ $$aOrr, Nick$$b42
000132915 7001_ $$aSwerdlow, Anthony$$b43
000132915 7001_ $$aHall, Per$$b44
000132915 7001_ $$aPharoah, Paul D P$$b45
000132915 7001_ $$aSchmidt, Marjanka K$$b46
000132915 7001_ $$aEaston, Douglas F$$b47
000132915 7001_ $$aChatterjee, Nilanjan$$b48
000132915 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b49$$eLast author
000132915 7001_ $$aGarcía-Closas, Montserrat$$b50
000132915 773__ $$0PERI:(DE-600)1494592-7$$a10.1093/ije/dyx242$$gVol. 47, no. 2, p. 526 - 536$$n2$$p526 - 536$$tInternational journal of epidemiology$$v47$$x1464-3685$$y2018
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