Depression, anxiety, and the risk of cancer: An individual participant data meta-analysis

Lonneke van Tuijl*, Maartje Basten, Kuan-Yu Pan, Roel Vermeulen, Andrew W Boyd, Alison Teyhan

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

5 Citations (Scopus)
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Abstract

Background
Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium.

Methods
The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2).

Results
No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios [HRs], 1.06–1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04–1.23).

Conclusions
Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers.
Original languageEnglish
Pages (from-to)3287-3299
Number of pages13
JournalCancer
Volume129
Issue number20
Early online date7 Aug 2023
DOIs
Publication statusPublished - 15 Oct 2023

Bibliographical note

Funding Information:
The Healthy Life in an Urban Setting (HELIUS) study is conducted by the Amsterdam University medical centers, location AMC, and the Public Health Service of Amsterdam. Both organizations provide core support for HELIUS. The HELIUS study is also funded by the Dutch Heart Foundation, the Netherlands Organisation for Health Research and Development (ZonMw), the European Union (FP‐7), and the European Fund for the Integration of non‐EU immigrants (EIF).

Funding Information:
The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organisation for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. We are grateful to the study participants, the staff from the Rotterdam Study, and the participating general practitioners and pharmacists.

Funding Information:
We thank the Dutch Cancer Society (grant VU2017-8288). The UK Medical Research Council and Wellcome (reference 217065/Z/19/Z) and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children (ALSPAC). The linkage of ALSPAC to the cancer registry was funded by Wellcome (reference 086118). The infrastructure of the Netherlands Study of Depression and Anxiety study (http://www.nesda.nl) is funded via the Geestkracht program of the Netherlands Organisation for Health Research and Development (grant 10-000-1002) and financial contributions by the 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, and Rob Giel Onderzoekscentrum). The English Longitudinal Study of Ageing is funded by the National Institute on Aging (R01AG017644) and the National Institute for Health and Care Research (198/1074-02). The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The Trøndelag Health Study (HUNT) is a collaboration between the HUNT Research Centre (Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology), Trøndelag County Council, Central Norway Regional Health Authority, and Norwegian Institute of Public Health. This research has been conducted using Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) data under application 2019-103. The data used in this research were made available by the 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 Healthy Life in an Urban Setting (HELIUS) study is conducted by the Amsterdam University medical centers, location AMC, and the Public Health Service of Amsterdam. Both organizations provide core support for HELIUS. The HELIUS study is also funded by the Dutch Heart Foundation, the Netherlands Organisation 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 Organisation for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. We 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 the authors N.N. and Y.P., for their contribution. Lifelines is a multidisciplinary 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, sociodemographic, behavioral, physical, and psychological factors that contribute to the health and disease of the general population, with a special focus on multimorbidity and complex genetics. The Lifelines initiative has been made possible by a subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, University Medical Center Groningen, 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 the ALSPAC 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 research nurses: R. van Petersen (data manager); A. Vandersteen (study manager); and the members of the Utrecht Cardiovascular Cohort–Second Manifestations of Arterial Disease study group (UCC-SMART): 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 and Hypertension; M. C. Verhaar, Department of Nephrology and Hypertension; and F. L. J. Visseren (chair), Department of Vascular Medicine, University Medical Center Utrecht and Utrecht University. This study has used data from the Cancer Registry of Norway. The interpretation and reporting of these data are the sole responsibility of the authors, and no endorsement by the Cancer Registry of Norway is intended nor should it be inferred.

Funding Information:
This research has been conducted using Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) data under application 2019‐103. The data used in this research were made available by the 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.

Funding Information:
Lonneke A. van Tuijl has received grants and travel support from the Dutch Cancer Society (KWF). Maartje Basten has received grants from the KWF. Kuan‐Yu Pan has received grants from the Dutch Cancer Foundation. Joost Dekker has received grants from the KWF. Femke Lamers has received grants from the KWF. Ottar Bjerkeset has been a consultant for Nord University. Andy Boyd has received grants from the Medical Research Council. Philipp Frank has received grants from the Economic and Social Research Council. Trynke R. de Jong has been a consultant for Medische Biobank Noord–Nederland. Ina Rissanen has received grants from Orionin Tutkimussäätiö. Annelieke M. Roest has received grants and travel support from the KWF. Mandy Spaan has received grants from the Netherlands Cancer Institute. Kimberly D. van der Willik has been a consultant for Erasmus Medisch Centrum. Adelita V. Ranchor has received grants from the KWF. The other authors declare no conflicts of interest.

Funding Information:
We thank the Dutch Cancer Society (grant VU2017‐8288). The UK Medical Research Council and Wellcome (reference 217065/Z/19/Z) and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children (ALSPAC). The linkage of ALSPAC to the cancer registry was funded by Wellcome (reference 086118). The infrastructure of the Netherlands Study of Depression and Anxiety study ( http://www.nesda.nl ) is funded via the Geestkracht program of the Netherlands Organisation for Health Research and Development (grant 10‐000‐1002) and financial contributions by the 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, and Rob Giel Onderzoekscentrum). The English Longitudinal Study of Ageing is funded by the National Institute on Aging (R01AG017644) and the National Institute for Health and Care Research (198/1074‐02). The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Publisher Copyright:
© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

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