Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies.
BACKGROUND
An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified.


OBJECTIVE
To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes.


METHODS
Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. STUDY ELIGIBILITY CRITERIA (PICOS):


METHODS
diabetes patients.


METHODS
Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs.


RESULTS
Any incident cancer.


METHODS
Cohort and case-control studies.


RESULTS
42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer.


CONCLUSIONS
Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders.


CONCLUSIONS
Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.
Oystein
O
Karlstad
Jacob
J
Starup-Linde
Peter
P
Vestergaard
Vidar
V
Hjellvik
Marloes T
MT
Bazelier
Marjanka K
MK
Schmidt
Morten
M
Andersen
Anssi
A
Auvinen
Jari
J
Haukka
Kari
K
Furu
Frank
F
de Vries
Norwegian Institute of Public Health, P.O.Box 4404 Nydalen, N-0403 Oslo, Norway. oystein.karlstad@fhi.no.
Marie L
ML
De Bruin
D001943:Breast Neoplasms / Q000139:chemically induced; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000139:chemically induced; D003920:Diabetes Mellitus / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000009:adverse effects; D009369:Neoplasms / Q000453:epidemiology*; D064887:Observational Studies as Topic; D017594:Publication Bias; D012042:Registries; D012107:Research Design
D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine