A Colorectal Cancer Obesity Paradox

Despite substantial success in the laboratory in recent decades, cancer remains a major cause of morbidity and mortality. Colorectal cancer is the third most common cancer in the world, contributing to 8% of cancer deaths every year ¹. This disease is classically more prevalent in more developed nations, so its burden is substantial in countries like the United Kingdom.

In years gone by, both the causes of colorectal cancer and the factors that determined survival after diagnosis were poorly understood. Now both its causative agents and disease progression are far better understood. One key risk factor that has been identified for a number of decades is a poor diet
and the obesity that often follows and now so plagues particularly the Western world ².

It would be natural to suggest that something so clearly linked to colorectal cancer onset would also contribute to a worse prognosis once the disease has been diagnosed. However, in results presented at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer at the beginning of this month, by a group from Duke School of Medicine suggests the opposite may in fact be true.

This group suggested that obese Dukes’ Stage IV colorectal cancer patients, who represent the worst prognosis of all colorectal cancer patients due to the fact that their cancers have metastasised and spread to other tissues, survived longer than their ‘thinner’ counterparts. Patients the study received bevacizumab, marketed as Avastin, a drug that prevents new blood vessel growth and hence cancer spread whose manufacturers partly funded the study, in combination with traditional chemotherapy. The results, shown below, show that obese patients, defined by a Body Mass Index (BMI) of 30-35, survived on average 3 months longer than other groups. The difference is most striking between ‘normal’ BMIs and the overweight and obese groups. There does appear to be a cut-off point, above which increasing weight does not confer any more survival benefit.

Interestingly, there was no difference between the groups in terms of when their tumours stopped growing, termed progression-free survival. Therefore, obese patients derived some survival benefit other than stopping the growth of tumours.

The lead author of the study, Yousuf Zafer M.D, warned against reading too far into the results. The reasons behind this finding remain to be seen; it may be the case that overweight patients may be able to cope with more intensive chemotherapy. So, will burgers and ice cream form part of cancer care in years to come? Dr Zafer doesn’t think so, warning that obesity carries increased risks of numerous diseases, such as diabetes, that impact your quality of life. Indeed, if this study had in some way measured the health of the patients in each group, obesity may not have been seen as such a benefit.

This ‘obesity complex’, in which overweight or obese patients survive for longer with chronic diseases is not a new concept in medicine, though it certainly is controversial. It has been reported that both type 2 diabetes patients ³ and those with established cardiovascular disease survive significantly longer if they are overweight ⁴. Numerous explanations have been put forward, such as differences in blood vessel width, stronger heart and lung action and a better metabolic reserve, that is, how much much energy is available in times of energy deprivation, in obese patients. However, with some researchers casting doubt on whether the phenomenon exists, far more work is required in this area to clarify the benefits obesity might convey. Indeed, with statistical analyses such as these only telling us about a correlation and not cause-and-effect, creating animal models and designing controlled clinical studies will be of critical importance.

Bibliography

1. WHO World Cancer Report 2014
2. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update
   Project Report. Food, Nutrition, Physical Activity, and the Prevention of Colorectal Cancer. 2011
3. Costanzo P, Cleland JG, Pellicori P, Clark AL, Hepburn D, Kilpatrick ES, et al. The Obesity Paradox in Type 2 Diabetes Mellitus: Relationship of Body Mass Index to Prognosis: A Cohort Study. Ann Intern Med. 2015;162:610-618. doi:10.7326/M14-1551
4. Carl J. Lavie, Richard V. Milani, Hector O. Ventura, Obesity and Cardiovascular Disease: Risk Factor, Paradox, and Impact of Weight Loss, Journal of the American College of Cardiology, Volume 53, Issue 21, 26 May 2009, Pages 1925-1932, ISSN 0735-1097, http://dx.doi.org/10.1016/j.jacc.2008.12.068.