RT Journal Article
T1 Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort.
A1 Assi, Nada
A1 Rinaldi, Sabina
A1 Viallon, Vivian
A1 Dashti, S Ghazaleh
A1 Dossus, Laure
A1 Fournier, Agnes
A1 Cervenka, Iris
A1 Kvaskoff, Marina
A1 Turzanski-Fortner, Renee
A1 Bergmann, Manuela
A1 Boeing, Heiner
A1 Panico, Salvatore
A1 Ricceri, Fulvio
A1 Palli, Domenico
A1 Tumino, Rosario
A1 Grioni, Sara
A1 Sanchez-Perez, Maria-Jose
A1 Chirlaque, María-Dolores
A1 Bonet, Catalina
A1 Barricarte Gurrea, Aurelio
A1 Amiano Etxezarreta, Pilar
A1 Merino, Susana
A1 Bueno de Mesquita, H Bas
A1 van Gils, Carla H
A1 Onland-Moret, Charlotte
A1 Tjønneland, Anne
A1 Overvad, Kim
A1 Trichopoulou, Antonia
A1 Martimianaki, Georgia
A1 Karakatsani, Anna
A1 Key, Tim
A1 Christakoudi, Sofia
A1 Ellingjord-Dale, Merete
A1 Tsilidis, Kostas
A1 Riboli, Elio
A1 Kaaks, Rudolf
A1 Gunter, Marc J
A1 Ferrari, Pietro
K1 EPIC
K1 alcohol
K1 breast cancer
K1 hormonal signature
K1 mediation analysis
K1 sex steroids
AB 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.
PB John Wiley & Sons, Inc.
YR 2019
FD 2019-004-19
LK http://hdl.handle.net/10668/13807
UL http://hdl.handle.net/10668/13807
LA en
NO Assi N, Rinaldi S, Viallon V, Dashti SG, Dossus L, Fournier A,  et al. Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort. Int J Cancer. 2020 Feb 1;146(3):759-768
NO N. Assi was financially supported by a grant from the Fondation deFrance (FdF) supporting her postdoctoral research (grant number:00069254). T. Key was funded through a grant from Cancer Research UK(grant number: CRUK C8221/A19170). The steroids measurements usedin our study were (partly) funded by a grant from the German ResearchFoundation, Graduiertenkolleg 793: Epidemiology of communicable andchronic noncommunicable diseases and their interrelationships andthrough financial support from the National Cancer Institute (USA)(grant no. 1U01CA98216-01). The coordination of EPIC is financiallysupported by the European Commission (DG-SANCO) and the Interna-tional Agency for Research on Cancer. The national cohorts are supportedby Danish Cancer Society (Denmark); Ligue Contre le Cancer, InstitutGustave Roussy, Mutuelle Générale de l’Education Nationale, InstitutNational de la Santé et de la Recherche Médicale (INSERM) (France);Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and FederalMinistry of Education and Research (Germany); the Hellenic HealthFoundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry ofPublic Health, Welfare and Sports (VWS), Netherlands Cancer Registry(NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON(Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF),Statistics Netherlands (The Netherlands); Nordic Center of ExcellenceProgram on Food, Nutrition and Health. (Norway); Health ResearchFund (FIS), PI13/00061 to Granada), Regional Governments of Andalucía,Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC(RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Counciland County Councils of Skåne and Västerbotten (Sweden); CancerResearch UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolkand MR/M012190/1 to EPIC-Oxford) (United Kingdom). Our study wasdone independently and with no input from the funders. The funderswere not involved in the design, implementation, analysis or interpretationof the data.
DS RISalud
RD Apr 8, 2025