Does obesity reduce a bowel cancer patient’s chance of being cured by chemotherapy?

Cancer Research Bruce Blue Award

Bowel cancer is (generally) a disease of the elderly, and our population is aging. It is known that excess body weight raises the risk of getting bowel cancer, and the rate of obesity is increasing worldwide. However, the effect of obesity on cancer survival is unclear. Some studies have reported a decrease in survival in obese patients with bowel cancer, but other studies have not.

Several of the molecular factors which control the link between obesity and cancer have been identified, and insulin and insulin-like growth factor (IGF-1) appear to be the main candidates. Insulin and IGF-1 are often raised in obese people. We set out to investigate the effect of these obesity-related factors on bowel cancer cells grown in culture. We hypothesized that these factors would increase the tumour cells’ ability to resist chemotherapy.

We found that the cancer cells grew faster when grown with insulin or IGF-1. In addition, IGF-1 slightly increased resistance to the main chemotherapy agents used to treat bowel cancer patients. Insulin, on the other hand, could both increase or decrease resistance to the drugs, depending on the conditions.

Our most intriguing result was that one of the bowel cancer cell lines grew faster when grown with IGF-1 and very low dose chemotherapy. This finding might be clinically important, since it has been shown that these low drug doses can circulate for many days after the initial drug administration in cancer patients. In obese patients this is even more likely, as they are sometimes under-dosed when their chemotherapy dose is capped.

In summary, our findings in cell culture suggest that under-dosing in an obese setting could lead to increased tumour growth. It is vital to point out that our results are from a simple cell culture model, and that we have no proof, yet, that this happens in cancer patients. We have just started an animal study to address these questions. Future work in bowel cancer patients is needed to establish if chemotherapy-induced cell growth could be the reason for the poorer survival in some obese cancer patients.