The Effects of Obesity and Obesity-related Conditions on Colorectal Cancer Prognosis

From Cancer Control: Journal of the Moffitt Cancer Center
Erin M. Siegel, PhD, MPH; Cornelia M. Ulrich, PhD; Elizabeth M. Poole, PhD; Rebecca S. Holmes, MD, MPH; Paul B. Jacobsen, PhD; David Shibata, MD

Abstract
Background: Colorectal cancer is the second-leading cause of cancer death in the United States among men and women combined.
Refinements in screening, staging, and treatment strategies have improved survival from this disease, with over 65% of patients diagnosed with colorectal cancer surviving over 5 years after diagnosis.
In the prognosis of colorectal cancer, clinicopathological factors are important. However, modifiable prognostic factors are emerging as significant contributors to cancer outcomes, including obesity and obesity-related inflammation and metabolic conditions.

Methods: This report reviews the literature on obesity and obesity-related inflammation and metabolic disturbances and colorectal cancer outcomes (recurrence, disease-free survival, and/or mortality).
A PubMed search was conducted of all English-language papers published between August 2003 and 2009 and cited in MEDLINE.

Results: Primary research papers were reviewed for colorectal cancer outcomes related to obesity, inflammation, or metabolic conditions. An association between body size and colorectal cancer recurrence and possibly survival was found; however, reports have been inconsistent. These inconsistent findings may be due to the complex interaction between adiposity, physical inactivity, and dietary intake. Circulating prognostic markers such as C-reactive protein, insulin-like growth factor, and insulin, alone or in combination, have been associated with prognosis in observational studies and should be evaluated in randomized trials and considered for incorporation into surveillance.

Conclusions: The literature suggests that obesity and obesity-related inflammation and metabolic conditions contribute to the prognosis of colorectal cancer; however, comprehensive large scale trials are needed. Interventions to reduce weight and control inflammation and metabolic conditions, such as diabetes, need to be evaluated and rapidly translated to behavior guidelines for patients.

Introduction
In 2009, approximately 146,000 individuals were diagnosed with colorectal cancer in the United States, and more than 49,000 individuals died of this disease.[1]
This makes colorectal cancer the second leading cause of cancer death in the United States among men and women combined.[1] Despite refinements in screening, staging, and treatment strategies, over 35% of patients diagnosed with colorectal cancer die within 5 years of diagnosis. Only 40% of patients with colorectal cancer are diagnosed at a localized stage, for which 5-year survival rates are greater than 90%. The majority of patients are diagnosed with either regional or distant spread, and the 5-year survival rates at these stages are approximately 68% and 11%, respectively.[2]

At the same time, the number of colorectal cancer survivors in the population continues to increase. This trend is accelerated by the increasing compliance to screening and the availability of more effective colorectal cancer treatment regimens. In 2002, the National Cancer Institute and the Centers for Disease Control and Prevention estimated that there were 10.1 million survivors of all cancers in the United States, a number that has tripled since 1971.[3] Among these are more than 1 million colorectal cancer survivors. Unfortunately, most survivors remain at risk for colorectal cancer recurrence (about 30% for all stages) and continue to endure posttreatment effects during survivorship.

At the time of cancer diagnosis and during surveillance, prognostic factors are utilized by clinicians to predict the probable course of disease in each patient and the likely outcome of the disease. The current gold standard for cancer prognosis is clinicopathological staging. However, outcome is independently influenced by other factors: histological characteristics of the tumor, patient age, presentation of disease, and performance status. Recently, molecular testing for mutations has proven effective in predicting tumor response to chemo therapy.[4] However, while clinicopathological factors are important, modifiable factors are emerging as key predictors of patient prognosis.

One such factor is obesity, which is modifiable. Cancer patients are increasingly interested in what lifestyle-related measures can be taken to optimize their recovery, to prevent recurrent or secondary tumors, and to assist in their return to an active, healthy life.[5] Therefore, a review of modifiable prognostic factors for co lo rectal cancer is needed.
Obesity and obesity-related inflammation and metabolic conditions have been proposed as modifiable prognostic factors in colorectal cancer. This report reviews the evidence regarding the effects of obesity and the resulting chronic inflammation and metabolic disturbances on colorectal cancer outcomes (recurrence, disease-free survival, and/or mortality).