The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: An individual participant data meta-analysis

Kuan Yu Pan; Lonneke Van Tuijl; Maartje Basten; Judith J.M. Rijnhart; Alexander De Graeff; Joost Dekker; Mirjam I. Geerlings; Adriaan Hoogendoorn; Adelita V. Ranchor; Roel Vermeulen; Lützen Portengen; Adri C. Voogd; Jessica Abell; Philip Awadalla; Aartjan T.F. Beekman; Ottar Bjerkeset; Andy Boyd; Yunsong Cui; Philipp Frank; Henrike Galenkamp; Bert Garssen; Sean Hellingman; Monika Hollander; Martijn Huisman; Anke Huss; Melanie R. Keats; Almar A.L. Kok; Steinar Krokstad; Flora E. Van Leeuwen; Annemarie I. Luik; Nolwenn Noisel; Yves Payette; Brenda W.J.H. Penninx; Susan Picavet; Ina Rissanen; Annelieke M. Roest; Judith G.M. Rosmalen; Rikje Ruiter; Robert A. Schoevers; David Soave; Mandy Spaan; Andrew Steptoe; Karien Stronks; Erik R. Sund; Ellen Sweeney; Alison Teyhan; Emma L. Twait; Kimberly D. Van Der Willik; Femke Lamers

doi:10.1017/S0033291724000850

The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: An individual participant data meta-analysis

Kuan Yu Pan^*
, Lonneke Van Tuijl
, Maartje Basten
, Judith J.M. Rijnhart
, Alexander De Graeff
, Joost Dekker
, Mirjam I. Geerlings
, Adriaan Hoogendoorn
, Adelita V. Ranchor
, Roel Vermeulen
, Lützen Portengen
, Adri C. Voogd
, Jessica Abell
, Philip Awadalla
, Aartjan T.F. Beekman
, Ottar Bjerkeset
, Andy Boyd
, Yunsong Cui
, Philipp Frank
, Henrike Galenkamp

Bert Garssen, Sean Hellingman, Monika Hollander, Martijn Huisman, Anke Huss, Melanie R. Keats, Almar A.L. Kok, Steinar Krokstad, Flora E. Van Leeuwen, Annemarie I. Luik, Nolwenn Noisel, Yves Payette, Brenda W.J.H. Penninx, Susan Picavet, Ina Rissanen, Annelieke M. Roest, Judith G.M. Rosmalen, Rikje Ruiter, Robert A. Schoevers, David Soave, Mandy Spaan, Andrew Steptoe, Karien Stronks, Erik R. Sund, Ellen Sweeney, Alison Teyhan, Emma L. Twait, Kimberly D. Van Der Willik, Femke Lamers

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Background Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). Methods Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). Results Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). Conclusions Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Original language	English
Pages (from-to)	2744–2757
Number of pages	14
Journal	Psychological Medicine
Volume	54
Issue number	10
Early online date	29 Apr 2024
DOIs	https://doi.org/10.1017/S0033291724000850
Publication status	Published - Jul 2024

Bibliographical note

Publisher Copyright:
Copyright © The Author(s), 2024. Published by Cambridge University Press.

Funding

KWF Dutch Cancer Society, Grant Number: VU2017-8288. The UK Medical Research Council and Wellcome Trust (ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. The linkage of ALSPAC to the cancer register was funded by Wellcome (ref:086118). The infrastructure of the NESDA study ( www.nesda.nl ) is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (Grant No. 10-000-1002) and financial contributions by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Rob Giel Onderzoekscentrum). ELSA is funded by the National Institute on Aging (R01AG017644) and the National Institute for Health and Care Research (198/1074-02). The Trøndelag Health Study (HUNT) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology NTNU), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. This research has been conducted using Atlantic PATH data under application 2019-103. The data used in this research were made available by the Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) study, which is the Atlantic Canada regional component of the Canadian Partnership for Tomorrow’s Health funded by the Canadian Partnership Against Cancer and Health Canada. The views expressed herein represent the views of the authors and do not necessarily represent the views of Health Canada. The HELIUS study is conducted by the Amsterdam University Medical Centers, location AMC and the Public Health Service of Amsterdam. Both organizations provided core support for HELIUS. The HELIUS study is also funded by the Dutch Heart Foundation, the Netherlands Organization for Health Research and Development (ZonMw), the European Union (FP-7), and the European Fund for the Integration of non-EU immigrants (EIF). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. We thank the whole CARTaGENE team (https://cartagene. qc.ca/en/about), represented by authors NN and YP, for their contribution. Lifelines is a multi-disciplinary prospective population-based cohort study examining in a unique three-generation design the health and health-related behaviors of 167 729 persons living in the North of the Netherlands. It employs a broad range of investigative procedures in assessing the biomedical, socio-demographic, behavioral, physical, and psychological factors that contribute to the health and disease of the general population, with a special focus on multi-morbidity and complex genetics. The Lifelines initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG), Groningen University and the Provinces in the North of the Netherlands (Drenthe, Friesland, Groningen). We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. We gratefully acknowledge the contribution of the UCC-SMART research nurses; R. van Petersen (data-manager); A. Vandersteen (study manager) and the members of the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease-Studygroup (UCC-SMART-Study group): F.W. Asselbergs and H.M. Nathoe, Department of Cardiology; G.J. de Borst, Department of Vascular Surgery; M.L. Bots and M.I. Geerlings, Julius Center for Health Sciences and Primary Care; M.H. Emmelot-Vonk, Department of Geriatrics; P.A. de Jong and T. Leiner, Department of Radiology; A.T. Lely, Department of Gynecology and Obstetrics; N.P. van der Kaaij, Department of Cardiothoracic Surgery; L.J. Kappelle and Y.M. Ruigrok, Department of Neurology & Hypertension; M.C. Verhaar, Department of Nephrology & Hypertension, F.L.J. Visseren (chair), Department of Vascular Medicine, University Medical Center Utrecht and Utrecht University. The authors thank the participants of the OMEGA study, without whom this study would not have been possible. The authors thank the medical registries of the participating clinics for making patient selection possible, and all participating physicians for providing access to their patients’ medical records. KWF Dutch Cancer Society, Grant Number: VU2017-8288. The UK Medical Research Council and Wellcome Trust (ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. The linkage of ALSPAC to the cancer register was funded by Wellcome (ref:086118). The infrastructure of the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (Grant No. 10-000-1002) and financial contributions by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Rob Giel Onderzoekscentrum). ELSA is funded by the National Institute on Aging (R01AG017644) and the National Institute for Health and Care Research (198/1074-02). The Trøndelag Health Study (HUNT) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology NTNU), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. This research has been conducted using Atlantic PATH data under application 2019-103. The data used in this research were made available by the Atlantic Partnership for Tomorrow's Health (Atlantic PATH) study, which is the Atlantic Canada regional component of the Canadian Partnership for Tomorrow's Health funded by the Canadian Partnership Against Cancer and Health Canada. The views expressed herein represent the views of the authors and do not necessarily represent the views of Health Canada. The HELIUS study is conducted by the Amsterdam University Medical Centers, location AMC and the Public Health Service of Amsterdam. Both organizations provided core support for HELIUS. The HELIUS study is also funded by the Dutch Heart Foundation, the Netherlands Organization for Health Research and Development (ZonMw), the European Union (FP-7), and the European Fund for the Integration of non-EU immigrants (EIF). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. We thank the whole CARTaGENE team ( https://cartagene.qc.ca/en/about ), represented by authors NN and YP, for their contribution. Lifelines is a multi-disciplinary prospective population-based cohort study examining in a unique three-generation design the health and health-related behaviors of 167 729 persons living in the North of the Netherlands. It employs a broad range of investigative procedures in assessing the biomedical, socio-demographic, behavioral, physical, and psychological factors that contribute to the health and disease of the general population, with a special focus on multi-morbidity and complex genetics. The Lifelines initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG), Groningen University and the Provinces in the North of the Netherlands (Drenthe, Friesland, Groningen). We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. We gratefully acknowledge the contribution of the UCC-SMART research nurses; R. van Petersen (data-manager); A. Vandersteen (study manager) and the members of the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease-Studygroup (UCC-SMART-Study group): F.W. Asselbergs and H.M. Nathoe, Department of Cardiology; G.J. de Borst, Department of Vascular Surgery; M.L. Bots and M.I. Geerlings, Julius Center for Health Sciences and Primary Care; M.H. Emmelot-Vonk, Department of Geriatrics; P.A. de Jong and T. Leiner, Department of Radiology; A.T. Lely, Department of Gynecology and Obstetrics; N.P. van der Kaaij, Department of Cardiothoracic Surgery; L.J. Kappelle and Y.M. Ruigrok, Department of Neurology & Hypertension; M.C. Verhaar, Department of Nephrology & Hypertension, F.L.J. Visseren (chair), Department of Vascular Medicine, University Medical Center Utrecht and Utrecht University. The authors thank the participants of the OMEGA study, without whom this study would not have been possible. The authors thank the medical registries of the participating clinics for making patient selection possible, and all participating physicians for providing access to their patients' medical records.

Funders	Funder number
National Institute for Health and Care Research	198/1074-02
UCC-SMART
Helse Midt-Norge
HUNT Research Centre
Leids Universitair Medisch Centrum
Erasmus Universiteit Rotterdam
Department of Radiology
Rotterdam Study
Wellcome
UCC-SMART-Study
Ministerie van Economische Zaken
Norges Teknisk-Naturvitenskapelige Universitet
Department of Geriatrics
Research Institute for Diseases in the Elderly
Leiden University
Erasmus Medisch Centrum
Rijksuniversiteit Groningen
Partenariat Canadien Contre Le Cancer
Leiden University Medical Center
Department of Cardiothoracic Surgery
University of Groningen
Ministerie van Volksgezondheid, Welzijn en Sport
Public Health Service of Amsterdam
Fakultet for medisin og helsevitenskap, Norges Teknisk-Naturvitenskapelige Universitet
Trøndelag County Council
Hartstichting
KWF Kankerbestrijding
ARTerial disease-Studygroup
European Refugee Fund
Universiteit Leiden
Health Canada
Department of Obstetrics and Gynecology, Baylor College of Medicine
University of Bristol
Ministerie van Onderwijs, Cultuur en Wetenschap
ZonMw	10-000-1002
European Commission	FP-7
Norwegian Institute of Public Health	2019-103
Wellcome Trust	217065/Z/19/Z, 086118
Economic and Social Research Council	ES/X000567/1
Dutch Cancer Society	VU2017-8288
Medical Research Council	MR/X021556/1
National Institute on Aging	R01AG017644

Keywords

anxiety
cancer risk
depression
health behavior
IPD meta-analysis
mediation analysis

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Pan, K. Y., Van Tuijl, L., Basten, M., Rijnhart, J. J. M., De Graeff, A., Dekker, J., Geerlings, M. I., Hoogendoorn, A., Ranchor, A. V., Vermeulen, R., Portengen, L., Voogd, A. C., Abell, J., Awadalla, P., Beekman, A. T. F., Bjerkeset, O., Boyd, A., Cui, Y., Frank, P., ... Lamers, F. (2024). The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: An individual participant data meta-analysis. Psychological Medicine, 54(10), 2744–2757. https://doi.org/10.1017/S0033291724000850

@article{c2e9d28c510441708f641ab520af942e,

title = "The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: An individual participant data meta-analysis",

abstract = "Background Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). Methods Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). Results Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). Conclusions Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.",

keywords = "anxiety, cancer risk, depression, health behavior, IPD meta-analysis, mediation analysis",

author = "Pan, \{Kuan Yu\} and \{Van Tuijl\}, Lonneke and Maartje Basten and Rijnhart, \{Judith J.M.\} and \{De Graeff\}, Alexander and Joost Dekker and Geerlings, \{Mirjam I.\} and Adriaan Hoogendoorn and Ranchor, \{Adelita V.\} and Roel Vermeulen and L{\"u}tzen Portengen and Voogd, \{Adri C.\} and Jessica Abell and Philip Awadalla and Beekman, \{Aartjan T.F.\} and Ottar Bjerkeset and Andy Boyd and Yunsong Cui and Philipp Frank and Henrike Galenkamp and Bert Garssen and Sean Hellingman and Monika Hollander and Martijn Huisman and Anke Huss and Keats, \{Melanie R.\} and Kok, \{Almar A.L.\} and Steinar Krokstad and \{Van Leeuwen\}, \{Flora E.\} and Luik, \{Annemarie I.\} and Nolwenn Noisel and Yves Payette and Penninx, \{Brenda W.J.H.\} and Susan Picavet and Ina Rissanen and Roest, \{Annelieke M.\} and Rosmalen, \{Judith G.M.\} and Rikje Ruiter and Schoevers, \{Robert A.\} and David Soave and Mandy Spaan and Andrew Steptoe and Karien Stronks and Sund, \{Erik R.\} and Ellen Sweeney and Alison Teyhan and Twait, \{Emma L.\} and \{Van Der Willik\}, \{Kimberly D.\} and Femke Lamers",

note = "Publisher Copyright: Copyright {\textcopyright} The Author(s), 2024. Published by Cambridge University Press.",

year = "2024",

month = jul,

doi = "10.1017/S0033291724000850",

language = "English",

volume = "54",

pages = "2744–2757",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

number = "10",

}

Pan, KY, Van Tuijl, L, Basten, M, Rijnhart, JJM, De Graeff, A, Dekker, J, Geerlings, MI, Hoogendoorn, A, Ranchor, AV, Vermeulen, R, Portengen, L, Voogd, AC, Abell, J, Awadalla, P, Beekman, ATF, Bjerkeset, O, Boyd, A, Cui, Y, Frank, P, Galenkamp, H, Garssen, B, Hellingman, S, Hollander, M, Huisman, M, Huss, A, Keats, MR, Kok, AAL, Krokstad, S, Van Leeuwen, FE, Luik, AI, Noisel, N, Payette, Y, Penninx, BWJH, Picavet, S, Rissanen, I, Roest, AM, Rosmalen, JGM, Ruiter, R, Schoevers, RA, Soave, D, Spaan, M, Steptoe, A, Stronks, K, Sund, ER, Sweeney, E, Teyhan, A, Twait, EL, Van Der Willik, KD & Lamers, F 2024, 'The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: An individual participant data meta-analysis', Psychological Medicine, vol. 54, no. 10, pp. 2744–2757. https://doi.org/10.1017/S0033291724000850

TY - JOUR

T1 - The mediating role of health behaviors in the association between depression, anxiety and cancer incidence

T2 - An individual participant data meta-analysis

AU - Pan, Kuan Yu

AU - Van Tuijl, Lonneke

AU - Basten, Maartje

AU - Rijnhart, Judith J.M.

AU - De Graeff, Alexander

AU - Dekker, Joost

AU - Geerlings, Mirjam I.

AU - Hoogendoorn, Adriaan

AU - Ranchor, Adelita V.

AU - Vermeulen, Roel

AU - Portengen, Lützen

AU - Voogd, Adri C.

AU - Abell, Jessica

AU - Awadalla, Philip

AU - Beekman, Aartjan T.F.

AU - Bjerkeset, Ottar

AU - Boyd, Andy

AU - Cui, Yunsong

AU - Frank, Philipp

AU - Galenkamp, Henrike

AU - Garssen, Bert

AU - Hellingman, Sean

AU - Hollander, Monika

AU - Huisman, Martijn

AU - Huss, Anke

AU - Keats, Melanie R.

AU - Kok, Almar A.L.

AU - Krokstad, Steinar

AU - Van Leeuwen, Flora E.

AU - Luik, Annemarie I.

AU - Noisel, Nolwenn

AU - Payette, Yves

AU - Penninx, Brenda W.J.H.

AU - Picavet, Susan

AU - Rissanen, Ina

AU - Roest, Annelieke M.

AU - Rosmalen, Judith G.M.

AU - Ruiter, Rikje

AU - Schoevers, Robert A.

AU - Soave, David

AU - Spaan, Mandy

AU - Steptoe, Andrew

AU - Stronks, Karien

AU - Sund, Erik R.

AU - Sweeney, Ellen

AU - Teyhan, Alison

AU - Twait, Emma L.

AU - Van Der Willik, Kimberly D.

AU - Lamers, Femke

PY - 2024/7

Y1 - 2024/7

N2 - Background Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). Methods Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). Results Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). Conclusions Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

AB - Background Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). Methods Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). Results Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). Conclusions Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

KW - anxiety

KW - cancer risk

KW - depression

KW - health behavior

KW - IPD meta-analysis

KW - mediation analysis

UR - https://www.scopus.com/pages/publications/85192083845

UR - https://www.scopus.com/pages/publications/85192083845#tab=citedBy

U2 - 10.1017/S0033291724000850

DO - 10.1017/S0033291724000850

M3 - Article

AN - SCOPUS:85192083845

SN - 0033-2917

VL - 54

SP - 2744

EP - 2757

JO - Psychological Medicine

JF - Psychological Medicine

IS - 10

ER -

The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: An individual participant data meta-analysis

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