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

Abstract

Background: Multiple 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.

Aim: To gain insight into the influence of a diabetic environment on colon cancer characteristics and outcomes.

Material and methods: Retrospective 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.

Results: The 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.

Conclusion: Our findings point towards a mild or negligible effect of the diabetes environment on colon cancer behavior, once cancer has already developed.

Fig 1. Schematic representation of the cancer xenograft model in mice.

Fig 2. Overview of the stratified data, provided by the medical records of patients at Fundacion Jimenez Diaz.

Fig 3. A diabetic environment does not modify tumor xenograft growth in mice.

A) Blood glucose levels in diabetic and control mice during the experiment. The cutoff point to define development of diabetes was established at 200 mg/dl; B) Representative images of tumors from diabetic and control mice; C) Tumor growth curves for xenografts in diabetic and control mice.

Fig 4. Representative histological images and corresponding quantification of vascular structures in the tumor xenograft model in mice.

A) and B) show hematoxylin-eosin staining and CD31 immunohistochemistry images in tumor samples from control and diabetic xenografts. Original magnification x200. Arrows indicate vascular structures. C) Graphical representation of the number of vascular structures/10 microscopic x200 fields in control and diabetic mice. Scale, bar, 100 μm.