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000143787 1001_ $$00000-0002-0629-3989$$aAssi, Nada$$b0
000143787 245__ $$aMediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort.
000143787 260__ $$aBognor Regis$$bWiley-Liss$$c2020
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000143787 500__ $$a2020 Feb 1;146(3):759-768
000143787 520__ $$aAlcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.
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000143787 7001_ $$00000-0002-6846-1204$$aRinaldi, Sabina$$b1
000143787 7001_ $$aViallon, Vivian$$b2
000143787 7001_ $$00000-0002-1399-7220$$aDashti, S Ghazaleh$$b3
000143787 7001_ $$aDossus, Laure$$b4
000143787 7001_ $$aFournier, Agnès$$b5
000143787 7001_ $$aCervenka, Iris$$b6
000143787 7001_ $$00000-0002-4557-3772$$aKvaskoff, Marina$$b7
000143787 7001_ $$0P:(DE-He78)74a6af8347ec5cbd4b77e562e10ca1f2$$aTurzanski-Fortner, Renée$$b8$$udkfz
000143787 7001_ $$aBergmann, Manuela$$b9
000143787 7001_ $$aBoeing, Heiner$$b10
000143787 7001_ $$aPanico, Salvatore$$b11
000143787 7001_ $$00000-0001-8749-9737$$aRicceri, Fulvio$$b12
000143787 7001_ $$aPalli, Domenico$$b13
000143787 7001_ $$aTumino, Rosario$$b14
000143787 7001_ $$aGrioni, Sara$$b15
000143787 7001_ $$aSánchez Pérez, María José$$b16
000143787 7001_ $$aChirlaque, María-Dolores$$b17
000143787 7001_ $$aBonet, Catalina$$b18
000143787 7001_ $$aGurrea, Aurelio Barricarte$$b19
000143787 7001_ $$aAmiano Etxezarreta, Pilar$$b20
000143787 7001_ $$aMerino, Susana$$b21
000143787 7001_ $$aBueno de Mesquita, H Bas$$b22
000143787 7001_ $$avan Gils, Carla H$$b23
000143787 7001_ $$aOnland-Moret, Charlotte$$b24
000143787 7001_ $$aTjønneland, Anne$$b25
000143787 7001_ $$aOvervad, Kim$$b26
000143787 7001_ $$aTrichopoulou, Antonia$$b27
000143787 7001_ $$aMartimianaki, Georgia$$b28
000143787 7001_ $$aKarakatsani, Anna$$b29
000143787 7001_ $$aKey, Tim$$b30
000143787 7001_ $$aChristakoudi, Sofia$$b31
000143787 7001_ $$aEllingjord-Dale, Merete$$b32
000143787 7001_ $$00000-0002-8452-8472$$aTsilidis, Kostas$$b33
000143787 7001_ $$aRiboli, Elio$$b34
000143787 7001_ $$0P:(DE-He78)4b2dc91c9d1ac33a1c0e0777d0c1697a$$aKaaks, Rudolf$$b35$$udkfz
000143787 7001_ $$aGunter, Marc J$$b36
000143787 7001_ $$aFerrari, Pietro$$b37
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