Obesity and colon cancer: does leptin provide a link?
Obesity, a risk factor for colorectal cancer, is associated with elevated serum levels of leptin, the adipocyte-derived hormone, and insulin. Experimental and epidemiologic studies have indicated a role for insulin in the pathogenesis of colon cancer, and recent experimental studies have suggested a similar role for leptin. In a case-control study nested in the Janus Biobank, Norway, we measured serum levels of leptin and C-peptide (a marker of pancreatic insulin secretion) in cryopreserved prediagnostic sera from men (median age, 45 years) who were diagnosed with cancer of the colon (n = 235) or rectum (n = 143) after blood collection (median time, 17 years), and among 378 controls matched for age and date of blood collection. Conditional logistic regression analyses showed an approximately 3-fold increase in colon cancer risk with increasing concentrations of leptin up to an odds ratio (OR) of 2.72 (95% CI = 1.44-5.12) for top vs. bottom quartile (p(trend) = 0.008). The corresponding OR for C-peptide was 1.81 (95% CI = 0.67-4.86; p(trend) = 0.19). The risk estimates remained unchanged after mutual adjustment. No association of hormone levels with rectal cancer risk was found. Reproducibility of hormone measurements assessed by intraclass coefficients (ICCs) for paired samples taken 1 year apart was high for leptin (ICC = 0.82) but lower for C-peptide (ICC = 0.30). Our results suggest that leptin is a risk factor for colon cancer, and that leptin may provide a link between obesity and colon cancer. Leptin may be directly involved in colon tumorigenesis or it may serve as a sensitive and robust marker of an obesity-induced adverse endocrine environment. Only weak support for an association of insulin with colon cancer was found.
Stattin
Pär
P
Department of Urology and Andrology, Umeå University Hospital, Umeå, Sweden. par.stattin@urologi.umu.se
Lukanova
Annekatrin
A
Biessy
Carine
C
Söderberg
Stefan
S
Palmqvist
Richard
R
Kaaks
Rudolf
R
Olsson
Tommy
T
Jellum
Egil
E
D000328:Adult; D002096:C-Peptide / Q000737:chemistry; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000209:etiology*; D015179:Colorectal Neoplasms / Q000097:blood; D015925:Cryopreservation; D006801:Humans; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism / Q000502:physiology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000209:etiology*; D016017:Odds Ratio; D012042:Registries; D013997:Time Factors
D002096:C-Peptide; D007328:Insulin; D020738:Leptin