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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: https://doi.org/10.1002/ijc.32324 |
It is part of: | International Journal of Cancer, 2019, vol. 146, num. 3, p. 759-768 |
URI: | http://hdl.handle.net/2445/174350 |
Related resource: | https://doi.org/10.1002/ijc.32324 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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assi_alc_bc_2019.pdf | 144.15 kB | Adobe PDF | View/Open |
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