One theory of increased colon cancer risk in Type 2 diabetes

Lack of association of colonic epithelium telomere length and oxidative DNA damage in Type 2 diabetes under good metabolic control
Original source: BMC Endocrine Disorders 2008, 8:12
Authors: Deepak Kejariwal (corresponding author), Karolina M Stepien, Tracy Smith, Hugh Kennedy, David A Hughes, and Mike J Sampson
Publication date: 10 October 2008
DOI (digital document ID): 10.1186/1472-6823-8-12
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
People with Type 2 diabetes are at greatly increased risk for developing colon cancer, but the reasons for this are not clear. One possible reason may be DNA damage and oxidative stress, which may or may not be related to high blood glucose levels. Telomeres are DNA repeat sequences at the ends of chomosomes that get shorter each time a cell divides. After a certain point, they become non-functional. This causes a chemical signal to go out to kill the cell, preventing the growth of tumors. If the chemical signal is missing, the cells will continue to divide and the chromosomes will become unstable. Eventually this instability and continued cell division can result in tumors. The loss of this signal is found in many cancers, including about half of all colorectal cancers.

Under oxidative stress, telomeres may shorten more quickly, and less accurately, than they might otherwise. The authors believed that the telomeres of people with Type 2 diabetes are more prone to the effects of oxidative stress than those without diabetes, and that the cells from their colons would show evidence of shorter telomeres, which would kick off a series of events leading to colorectal cancer.

People with lower-intestinal and colon disease were excluded from this study, as were those who took vitamins or fish oil. The patients controlled their diabetes by taking metformin, a sulfonylurea drug, both of those, or insulin. A total of 32 people were examined between the people with diabetes and the non-diabetic controls. None of the subjects were smokers. The diabetic subjects had A1c under 6.9% but were dealing with known complications of diabetes. Tissue samples were taken from the lower colon and examined for oxidative damage and telomere shortening.

There were no appreciable differences in telomere length between the two groups. However, the groups were small, and the greater number of people with diabetes taking aspirin, ACE inhibitors (anti-hypertension medication), and/or statins (to reduce high cholesterol levels) may have provided some level of protection. Other reasons a difference was not seen could be that the diabetic subjects were in good control of their blood glucose levels, and that 6.5 years may not be a long enough time with diabetes for the effects of oxidative stress and increased colon cancer risk to be measurable.

Reliability:
Two of the investigators associated with a University hospital. The research was published in a peer-reviewed journal. The sample size was extremely small, and though steps were taken to minimize its effects, this small a sample could cause a skewed set of results. The authors do suggest that further research is necessary to confirm or rule out their theory.

Practical Applications:
More research is needed to find out exactly why people with Type 2 diabetes are at higher risk of developing colon cancer, and ways of minimizing that additional risk.

This synopsis was based on the entire article.