Colon cancer modulation by a diabetic environment: A single institutional experience

Abstract

BackgroundMultiple observational studies suggest an increased risk of colon cancer in patients with diabetes mellitus (DM). This can theoretically be the result of an influence of the diabetic environment on carcinogenesis or the tumor biologic behavior.AimTo gain insight into the influence of a diabetic environment on colon cancer characteristics and outcomes.Material and methodsRetrospective analysis of clinical records in an academic tertiary care hospital with detailed analysis of 81 diabetic patients diagnosed of colon cancer matched with 79 non-diabetic colon cancer patients. The impact of streptozotocin-induced diabetes on the growth of colon cancer xenografts was studied in mice.ResultsThe incidence of DM in 1,137 patients with colorectal cancer was 16%. The diabetic colon cancer cases and non-diabetic colon cancer controls were well matched for demographic and clinical variables. The ECOG Scale Performance Status was higher (worse) in diabetics (ECOG ≥1, 29.1% of controls vs 46.9% of diabetics, p = 0.02), but no significant differences were observed in tumor grade, adjuvant therapy, tumor site, lymphovascular invasion, stage, recurrence, death or cancer-related death. Moreover, no differences in tumor variables were observed between patients treated or not with metformin. In the xenograft model, tumor growth and histopathological characteristics did not differ between diabetic and nondiabetic animals.ConclusionOur findings point towards a mild or negligible effect of the diabetes environment on colon cancer behavior, once cancer has already developed.

Molecular evidence of field cancerization initiated by diabetes in colon cancer patients

“…A). These results are consistent with our previous clinical and epidemiological study using the same cohort (Prieto et al ., ). Concurrently, a differential expression analysis of the transcriptomic data disclosed no up‐ or downregulated genes under T2DM conditions when false discovery rate (FDR)‐adjusted P ‐value <0.05 was used.…”

“…Patients were recruited from January 2009 to December 2013 at the Fundación Jiménez Díaz Hospital (Madrid, Spain). The same cohort was used in a previous epidemiological study (Prieto et al ., ). The inclusion parameters were as follows: patients with resection of primary colon cancer, colon adenocarcinoma histological type, colon location (rectal cancer patients were excluded), time from surgery up to 6 months, no neoadjuvant treatment, no other concurrent neoplasia or immunosuppressive treatment, and diabetes diagnosed as a documented registry of diabetes, or historical antidiabetic medication intake or meeting the American Diabetic Association (ADA) criteria for diabetes at time of reviewing the data.…”

“…In parallel, this observational study also included 79 nondiabetic patients with primary diagnosis of colon cancer, who underwent resection during the same period, using equal inclusion criteria except the presence of diabetes, aiming to obtain a well‐balanced series. No significant differences in body mass index (BMI) were observed between diabetics and nondiabetics (Prieto et al ., ).…”

“…Tumor xenografts in mice with streptozotocin‐induced diabetes were developed using methods extensively described in our previous report (Prieto et al ., ). Briefly, 8‐week‐old athymic mice NU‐Foxn1nu (15 mice) (Charles River Laboratories, Wilmington, MA, USA) were injected with 200 mg·kg −1 body weight streptozotocin (STZ, Sigma‐Aldrich, Darmstadt, Germany) to achieve a diabetic environment.…”

“…While several cohort studies and meta‐analyses have reported an increased risk for CC development in T2DM patients (Larsson et al ., ; Sun and Yu, ) as well as a higher short‐ and long‐term mortality (Croft et al ., ; Zhu et al ., ), others identified biases produced by the size and origin of the populations studied (de Jong et al ., ; Tsilidis et al ., ). Our own experience using a highly homogeneous Spanish cohort indicated that even if there is a higher risk of cancer development, the effect of diabetes does not entail a worse outcome once the tumor has developed (Prieto et al ., ). In any case, the controversies generated by the different observational studies have strengthened the need to study the molecular mechanisms behind a possible association between both diseases, today still unclear.…”