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

被引：14

作者：

Assi, Nada ^{[1
]}

Rinaldi, Sabina ^{[2
]}

Viallon, Vivian ^{[1
]}

Dashti, S. Ghazaleh ^{[1
,3
]}

Dossus, Laure ^{[1
]}

Fournier, Agnes ^{[4
,5
,6
]}

Cervenka, Iris ^{[4
,5
]}

Kvaskoff, Marina ^{[4
,5
]}

Turzanski-Fortner, Renee ^{[7
]}

Bergmann, Manuela ^{[8
]}

Boeing, Heiner ^{[8
]}

Panico, Salvatore ^{[9
]}

Ricceri, Fulvio ^{[10
,11
]}

Palli, Domenico ^{[12
]}

Tumino, Rosario ^{[13
]}

Grioni, Sara ^{[14
]}

Sanchez Perez, Maria Jose ^{[15
,16
]}

Chirlaque, Maria-Dolores ^{[15
,17
,18
]}

Bonet, Catalina ^{[19
]}

Barricarte Gurrea, Aurelio ^{[15
,20
,21
,22
]}

Amiano Etxezarreta, Pilar ^{[15
,23
]}

Merino, Susana ^{[24
]}

de Mesquita, H. Bas Bueno ^{[25
,26
,27
,28
]}

van Gils, Carla H. ^{[29
]}

Onland-Moret, Charlotte ^{[29
]}

Tjonneland, Anne ^{[30
,31
]}

Overvad, Kim ^{[32
]}

Trichopoulou, Antonia ^{[33
]}

Martimianaki, Georgia ^{[33
]}

Karakatsani, Anna ^{[33
,34
]}

Key, Tim ^{[35
]}

Christakoudi, Sofia ^{[27
,36
]}

Ellingjord-Dale, Merete ^{[27
]}

Tsilidis, Kostas ^{[27
,37
]}

Riboli, Elio ^{[27
]}

Kaaks, Rudolf ^{[7
]}

Gunter, Marc J. ^{[6
]}

Ferrari, Pietro ^{[1
]}

机构：

[1] Int Agcy Res Canc IARC, Nutr Methodol & Biostat Grp, Lyon, France

[2] Int Agcy Res Canc IARC, Biomarkers Grp, Lyon, France

[3] Univ Melbourne, Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Parkville, Vic, Australia

[4] Univ Paris Saclay, Univ Paris Sud, CESP, Fac Med,UVSQ,INSERM, Villejuif, France

[5] Gustave Roussy, Villejuif, France

[6] Int Agcy Res Canc IARC, Nutr Epidemiol Grp, Lyon, France

[7] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[8] German Inst Human Nutr, Dept Epidemiol, Nuthetal, Germany

[9] Univ Naples Federico II, Dipartimento Med Clin & Chirurg, Naples, Italy

[10] Univ Turin, Dept Clin & Biol Sci, Turin, Italy

[11] Reg Hlth Serv ASL TO3, Epidemiol Unit, Grugliasco, Italy

[12] Inst Canc Res Prevent & Clin Network ISPRO, Canc Risk Factors & Life Style Epidemiol Unit, Florence, Italy

[13] Civ M P Arezzo, Canc Registry & Histopathol Dept, Ragusa, Italy

[14] Ist Nazl Tumori Milano, Fdn IRCCS, Epidemiol & Prevent Unit, Milan, Italy

[15] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain

[16] Univ Granada, IBS GRANADA, Inst Invest Biosanitaria, Escuela Andaluza Salud Publ, Granada, Spain

[17] IMIB Arrixaca, Reg Hlth Council, Dept Epidemiol, Murcia, Spain

[18] Univ Murcia, Dept Hlth & Social Sci, Murcia, Spain

[19] Inst Catala Oncol, Canc Epidemiol Res Program, Unit Nutr & Canc, Lhospitalet De Llobregat, Spain

[20] Navarra Publ Hlth Inst, Pamplona, Spain

[21] Navarra Publ Hlth Inst, Pamplona, Spain

[22] Navarra Inst Hlth Res IdiSNA, Pamplona, Spain

[23] BioDonostia Res Inst, Publ Hlth Div Gipuzkoa, San Sebastian, Spain

[24] Publ Hlth Directorate, Asturias, Spain

[25] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven, Netherlands

[26] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands

[27] Imperial Coll London, MRC HPA Ctr Environm & Hlth, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England

[28] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia

[29] Canc Epidemiol Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[30] Danish Canc Soc, Res Ctr, Copenhagen, Denmark

[31] Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark

[32] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, Aarhus, Denmark

[33] Hellen Hlth Fdn, Athens, Greece

[34] Natl & Kapodistrian Univ Athens, ATTIKON Univ Hosp, Sch Med, Dept Pulm Med, Haidari, Greece

[35] Univ Oxford, Canc Epidemiol Unit, Oxford, England

[36] Kings Coll London, MRC Ctr Transplantat, London, England

[37] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece

来源：

INTERNATIONAL JOURNAL OF CANCER | 2020年 / 146卷 / 03期

基金：

英国医学研究理事会;

关键词：

sex steroids; alcohol; breast cancer; mediation analysis; hormonal signature; EPIC; COLLABORATIVE REANALYSIS; FREE TESTOSTERONE; RISK-FACTORS; WOMEN; SERUM; CONSUMPTION; PREMENOPAUSAL; ESTROGEN; PROJECT; PATTERNS;

D O I：

10.1002/ijc.32324

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. What's new? Alcohol consumption is associated with an increased risk of breast cancer (BC). However, the mechanisms underlying this association are not yet fully understood. For example, do sex-hormone levels play a role? In this study, the authors assessed a number of alcohol-related hormonal signatures. They found that lower levels of sex-hormone binding globulin (SHBG), combined with higher levels of sex steroids, mediate a substantial proportion of the observed alcohol-BC association. It is likely that the mechanism involves the interplay of multiple hormones, rather than the action of individual hormones.

引用

页码：759 / 768

页数：10

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