Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2020 Feb 1;146(3):759-768.
doi: 10.1002/ijc.32324. Epub 2019 Apr 30.

Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort

Nada Assi  1 , Sabina Rinaldi  2 , Vivian Viallon  1 , S Ghazaleh Dashti  1   3 , Laure Dossus  1 , Agnès Fournier  4   5   6 , Iris Cervenka  4   5 , Marina Kvaskoff  4   5 , Renée Turzanski-Fortner  7 , Manuela Bergmann  8 , Heiner Boeing  8 , Salvatore Panico  9 , Fulvio Ricceri  10   11 , Domenico Palli  12 , Rosario Tumino  13 , Sara Grioni  14 , María José Sánchez Pérez  15   16 , María-Dolores Chirlaque  15   17   18 , Catalina Bonet  19 , Aurelio Barricarte Gurrea  15   20   21 , Pilar Amiano Etxezarreta  15   22 , Susana Merino  23 , H Bas Bueno de Mesquita  24   25   26   27 , Carla H van Gils  28 , Charlotte Onland-Moret  28 , Anne Tjønneland  29   30 , Kim Overvad  31 , Antonia Trichopoulou  32 , Georgia Martimianaki  32 , Anna Karakatsani  32   33 , Tim Key  34 , Sofia Christakoudi  26   35 , Merete Ellingjord-Dale  26 , Kostas Tsilidis  26   36 , Elio Riboli  26 , Rudolf Kaaks  7 , Marc J Gunter  6 , Pietro Ferrari  1
Affiliations
Multicenter Study

Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort

Nada Assi et al. Int J Cancer. .

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.

Keywords: EPIC; alcohol; breast cancer; hormonal signature; mediation analysis; sex steroids.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interests Statement

The authors declare no potential conflicts of interest.

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA Cancer J Clin [Internet]. American Cancer Society; 2018. [cited 2018 Oct 4]; Available from: http://doi.wiley.com/10.3322/caac.21492 - DOI - PubMed
    1. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F. Global Cancer Observatory: Cancer Tomorrow Lyon, France: International Agency for Research on Cancer; 2018.
    1. Anothaisintawee T, Wiratkapun C, Lerdsitthichai P, Kasamesup V, Wongwaisayawan S, Srinakarin J, Hirunpat S, Woodtichartpreecha P, Boonlikit S, Teerawattananon Y, et al. Risk factors of breast cancer: a systematic review and meta-analysis. Asia Pac J Public Health. 2013;25:368–87. - PubMed
    1. Baan R, Straif K, Grosse Y, El Ghissassi F, Bouvard V, Altieri A, Cogliano VJ, WHO International Agency for Research on Cancer Monograph Working Group. Carcinogenicity of alcoholic beverages. Lancet Oncol. 2007;8:292–3. - PubMed
    1. Collaborative Group on Hormonal Factors in Breast Cancer. Alcohol , tobacco and breast cancer – collaborative reanalysis of individual data from 53 epidemiological studies , including 58 , 515 women with breast cancer and 95 , 067 women without the disease . Collaborative Group On Hormonal Factors In Breast Canc. Br J Cancer. 2002;87:1234–1245. - PMC - PubMed

Publication types