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@article{Assi:2020:10.1002/ijc.32324,
author = {Assi, N and Rinaldi, S and Viallon, V and Dashti, SG and Dossus, L and Fournier, A and Cervenka, I and Kvaskoff, M and Turzanski-Fortner, R and Bergmann, M and Boeing, H and Panico, S and Ricceri, F and Palli, D and Tumino, R and Grioni, S and Sánchez, Pérez MJ and Chirlaque, M-D and Bonet, C and Gurrea, AB and Amiano, Etxezarreta P and Merino, S and Bueno, de Mesquita HB and van, Gils CH and Onland-Moret, C and Tjønneland, A and Overvad, K and Trichopoulou, A and Martimianaki, G and Karakatsani, A and Key, T and Christakoudi, S and Ellingjord-Dale, M and Tsilidis, K and Riboli, E and Kaaks, R and Gunter, MJ and Ferrari, P},
doi = {10.1002/ijc.32324},
journal = {International Journal of Cancer},
pages = {759--768},
title = {Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort},
url = {http://dx.doi.org/10.1002/ijc.32324},
volume = {146},
year = {2020}
}

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TY  - JOUR
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.
AU  - Assi,N
AU  - Rinaldi,S
AU  - Viallon,V
AU  - Dashti,SG
AU  - Dossus,L
AU  - Fournier,A
AU  - Cervenka,I
AU  - Kvaskoff,M
AU  - Turzanski-Fortner,R
AU  - Bergmann,M
AU  - Boeing,H
AU  - Panico,S
AU  - Ricceri,F
AU  - Palli,D
AU  - Tumino,R
AU  - Grioni,S
AU  - Sánchez,Pérez MJ
AU  - Chirlaque,M-D
AU  - Bonet,C
AU  - Gurrea,AB
AU  - Amiano,Etxezarreta P
AU  - Merino,S
AU  - Bueno,de Mesquita HB
AU  - van,Gils CH
AU  - Onland-Moret,C
AU  - Tjønneland,A
AU  - Overvad,K
AU  - Trichopoulou,A
AU  - Martimianaki,G
AU  - Karakatsani,A
AU  - Key,T
AU  - Christakoudi,S
AU  - Ellingjord-Dale,M
AU  - Tsilidis,K
AU  - Riboli,E
AU  - Kaaks,R
AU  - Gunter,MJ
AU  - Ferrari,P
DO  - 10.1002/ijc.32324
EP  - 768
PY  - 2020///
SN  - 0020-7136
SP  - 759
TI  - Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort
T2  - International Journal of Cancer
UR  - http://dx.doi.org/10.1002/ijc.32324
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30968961
UR  - http://hdl.handle.net/10044/1/69999
VL  - 146
ER  -

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