Obesity and Colorectal Cancer

Abstract

Obesity is a risk factor for colorectal cancer based on its molecular and metabolic effects on insulin and IGF-1, leptin, adipocytokines, and sex hormones. Obese men have a higher risk of colorectal cancer compared with normal weight men, but the association between obesity and rectal cancer is weaker than with colon cancer. There is a weaker association between obesity and colon cancer in women than in men, and no appreciable association between obesity and rectal cancer in women. Although obesity does not seem to have an effect on the number of lymph nodes harvested with resection, obesity does seem to be associated with more-aggressive colorectal cancers in a handful of studies. Survival and local recurrence studies are contradictory with no conclusive evidence that obesity predisposes to worse overall survival or increased recurrence in colon and rectal cancers. The literature is not definitive as far as overall morbidity and mortality rates in the obese are concerned, though obese rectal cancer patients seem to incur proportionally more morbidity and mortality. Preexisting steatosis or steatohepatitis in obese colorectal cancer patients or chemotherapy-induced liver dysfunction may lead to an increased mortality in obese patients with colorectal liver metastases. Diabetes may cause poorer response to neoadjuvant therapy in rectal cancer and contribute to higher mortality and recurrence in colon cancer.KEYWORDS: Obesity, colon cancer, rectal cancer, diabetes, men, women Objectives: After reading this review, the reader should be able to summarize how and why obesity is a risk factor for colorectal cancer, and have an appreciation for how definitions of obesity vary and impact study results. In addition, the reader should also understand the impact of obesity on colorectal cancer short-term outcomes, long-term oncologic outcomes, and how obesity can impact the chemotherapeutic treatment of metastatic disease.Colorectal cancer (CRC) is a major cause of cancer death in Western societies and it is well known that this elevated risk is related to an imbalance between neoplasia promoting and protective dietary and lifestyle factors. Among the factors that tend to elevate risk are a high intake of animal fat, high calorie intake, high intake of processed foods with low fiber content, limited physical activity, excess alcohol intake, and finally obesity.What follows is a discussion on how and why obesity is a risk factor for colorectal cancer and how obesity influences short-and long-term oncologic outcomes from a surgical, pathologic, radiotherapy, and chemotherapeutic perspective. The data leads one to conclude that obesity has implications in all aspects of the care of colorectal cancer patients, from screening to surgical treatment to adjuvant or neoadjuvant treatments.

Circulating Resistin Levels and Risk of Colorectal Cancer: A Meta-Analysis

“…CRC is recognized as a complex multipathway disease circled with chronic inflammation, metabolic syndrome, insulin resistance (IR), and obesity. The results from epidemiological evidence indicate that obesity is associated with increased incidence of CRC [3, 4]. Recent studies suggest that adipocyte-derived secretory factors including adiponectin, leptin, resistin, visfatin, and numerous cytokines including TNF-alpha, IL-6, and IL-10 may be the key to link obesity with CRC, although underlying mechanisms remain unexplained [5–8].…”

BMI and the risk of colorectal adenoma in African‐Americans

“…Although BMI cannot discriminate excess in body fat from increment in lean mass or fat distribution but it is the most common measurement used in studies worldwide . Because fat distribution location seems to be important in determining the risk of disease , complementary anthropometric methods such as waist circumference or waist‐to‐hip ratio or even waist‐to‐height ratio have now been used to depict adipose tissue distribution , however none of them except visceral fat measurement (abdominal obesity) are precise in measuring fat distribution accurately . Visceral fat is associated with insulin resistance and higher levels of circulating IGF‐1 .…”

Progastrin Peptides Increase the Risk of Developing Colonic Tumors: Impact on Colonic Stem Cells

“…Inflammation (due to IBD/obesity) (67,68) and infectious agents such as citrobacter-rodentium ( CR ), increase the risk for developing colonic-tumors (69). Significant synergistic effects of PG and CR infection were measured on hyperproliferation of colonic-crypts in mice, in relation to up-regulation of ERKs/NFκB/β-catenin (70).…”