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Title: Mediation analysis of the alcohol‐postmenopausal breast cancer relationship by sex hormones in the EPIC Cohort
Author: Assi, Nada
Rinaldi, Sabina
Viallon, Vivian
Dashti, S. Ghazaleh
Dossus, Laure
Fournier, Agnès
Cervenka, Iris
Kvaskoff, Marina
Fortner, Renée T.
Bergmann, Manuela M.
Boeing, Heiner
Panico, Salvatore
Ricceri, Fulvio
Palli, Domenico
Tumino, Rosario
Grioni, Sara
Sánchez Pérez, María José
Chirlaque, María Dolores
Bonet Bonet, Catalina
Barricarte, Aurelio
Amiano, Pilar
Merino, Susana
Bueno de Mesquita, H. Bas
Gils, Carla H.
Onland-Moret, N. Charlotte
Tjønneland, Anne
Overvad, Kim
Trichopoulou, Antonia
Martimianaki, Georgia
Karakatsani, Anna
Key, Tim
Christakoudi, Sofia
Ellingjord-Dale, Merete
Tsilidis, Kostas
Riboli, Elio
Kaaks, Rudolf
Gunter, Marc J.
Ferrari, Pietro
Keywords: Càncer de mama
Consum d'alcohol
Hormones sexuals
Breast cancer
Drinking of alcoholic beverages
Sex hormones
Issue Date: 30-Apr-2019
Publisher: Wiley
Abstract: Alcohol 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.
Note: Versió postprint del document publicat a:
It is part of: International Journal of Cancer, 2019, vol. 146, num. 3, p. 759-768
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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