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Evidence accumulated over the past decade has clearly established excess body fatness as a risk factor for colorectal cancer. Specifically, using body mass index (BMI) as an approximation of body fatness, risk increases with increasing BMI in a sex- (men>women) and site- (colon>rectum) specific manner.1 A number of plausible biological mechanisms may underpin these associations,2 including increased insulin resistance, increased availability of insulin-like growth factor (IGF)-I (mitogenic, pro-apoptotic, pro-angiogenic, increases cell motility), and altered adipokine metabolism; for example, increased leptin (mitogenic, anti-apoptotic, pro-angiogenic) and/or decreased adiponectin (anti-angiogenic, anti-inflammatory). Population-based cohort data report that increased BMI is also associated with an increased risk of colon cancer-related mortality suggesting that excess body weight impacts unfavourably on outcome in patients with established disease.3 However, the above study design is limited by lack of details on staging and treatment (key determinants of outcome), and hence, it remains unclear whether the increased mortality observed among obese individuals represents increased incidence, delayed diagnosis, differential primary treatment, differential selection for adjuvant therapies, increased risk from treatment-related complications and/or a differential response to treatment, compared with leaner counterparts. Addressing one possible mechanism of adverse treatment outcome, secondary analyses from at least two randomised trials of adjuvant 5-fluorouracil (5-FU)-based chemotherapies in patients with colon cancer demonstrate increased …
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