CARING (CAncer Risk and INsulin analoGues): The Association of Diabetes Mellitus and Cancer Risk with Focus on Possible Determinants - A Systematic Review and a Meta-Analysis
Jakob Starup-Linde, Øystein Karlstad, Stine Aistrup Eriksen, Peter Vestergaard, Heleen K. Bronsveld, Frank de Vries, Morten Andersen, Anssi Auvinen, Jari Haukka, Vidar Hjellvik, Marloes T. Bazelier, Anthonius de Boer, Kari Furu and Marie L. De Bruin
Affiliation: Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Tage Hansens Gade 2, 8000 Aarhus C, Denmark.
Keywords: Cancer risk, diabetes mellitus, meta-analysis, neoplasm, systematic review.
Background: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer;
however, it is not certain whether this effect is due to diabetes per se.
Objective: To examine the association between DM and cancers by a systematic review and meta-analysis according to
the PRISMA guidelines.
Data Sources: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane
library, Web of Science and SveMed+ with the search terms: “Diabetes mellitus”, “Neoplasms”, and “Risk of cancer”.
Study Eligibility Criteria: The included studies compared the risk of cancer in diabetic patients versus non-diabetic
patients. All types of observational study designs were included.
Results: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer.
Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial
(RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar
for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body
mass index, and possible effect modification of age, gender, with some influence of study characteristics (population
source, cancer- and diabetes ascertainment).
Limitations: Publication bias seemed to be present. Only published data were used in the analyses.
Conclusions: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes
and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes
patients are at an increased risk of cancer.
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