Abstract

BackgroundAnorexia nervosa is characterized by a severe restriction of caloric intake, low body weight, fear of gaining weight or of becoming fat, and disturbance of body image. Pathogenesis of the disorder may include genetic predisposition, hormonal changes and a combination of environmental, psychosocial, and cultural factors. Cancer is the second leading cause of death worldwide. At present, no systematic reviews and meta-analyses have evaluated the risk of cancer in people with anorexia nervosa. The objective of this study will be to evaluate the association between anorexia nervosa and the risk of developing or dying from cancer.Methods/designThis study protocol is part of a systematic collection and assessment of multiple systematic reviews and meta-analyses (umbrella review) evaluating the association of cancer and multiple central nervous system disorders. We designed a specific protocol for a new systematic review and meta-analysis of observational studies of anorexia nervosa with risk of developing or dying from any cancer. Data sources will be PubMed, Embase, Scopus, Web of Science, and manual screening of references. Observational studies (case–control and cohort) in humans that examined the association between anorexia nervosa and risk of developing or dying from cancer will be sought. The primary outcomes will be cancer incidence and cancer mortality in association with anorexia nervosa. Secondary outcomes will be site-specific cancer incidence and mortality, respectively. Screening of abstracts and full texts, and data abstraction will be performed by two team members independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. The quality of studies will be assessed by using the Ottawa-Newcastle scale by two team members independently. Random effects models will be conducted where appropriate. Subgroup and additional analyses will be conducted to explore the potential sources of heterogeneity. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for cancer outcomes.DiscussionFindings from this systematic review will inform an ongoing umbrella review on cancer and central nervous system disorders. Our systematic review and meta-analysis of observational studies will establish the extent of the epidemiological evidence underlying the association between anorexia nervosa and cancer.Systematic review registrationPROSPERO CRD42017067462.

Highlights

  • DiscussionFindings from this systematic review will inform an ongoing umbrella review on cancer and central nervous system disorders

  • Anorexia nervosa is characterized by a severe restriction of caloric intake, low body weight, fear of gaining weight or of becoming fat, and disturbance of body image

  • Our systematic review and meta-analysis of observational studies will establish the extent of the epidemiological evidence underlying the association between anorexia nervosa and cancer

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Summary

Discussion

The systematic review presented in this protocol will inform an ongoing umbrella review and meta-analysis of observational studies on cancer and central nervous system disorders [28]. Direct and inverse cancer comorbidity could be a relevant model to investigate common or related pathways or processes and test new therapies and prevention programs, but, most importantly, to understand why certain people might potentially be protected from the malignancy [25, 53, 54] In this context, understanding the complex connections between anorexia nervosa and cancer might be important for clinical research and practice. A key challenge is that based on knowledge from previous reviews on cancer and central nervous system disorders [54,55,56,57], we Abbreviations AICR: American Institute for Cancer Research; AMSTAR: Assessment of Multiple Systematic Reviews; DSM: Diagnostic and Statistical Manual of Mental Disorders; GRADE: Grading of Recommendations Assessment, Development, and Evaluation; ICD: International Classification of Diseases; MOOSE: Meta-analysis Of Observational Studies in Epidemiology; NOS: Newcastle-Ottawa scale; PRISMA-P: Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Protocols; WCRF: World Cancer Research Fund

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