Abstract
PurposeThe impact of weight loss on obesity-related colorectal cancer (CRC) risk is not well defined. Previous studies have suggested that Roux-en-Y gastric bypass (RYGB) surgery may have an unexpected adverse impact on CRC risk. This study aimed to investigate the impact of RYGB on biomarkers of CRC risk.Materials and methodsRectal mucosal biopsies and blood were obtained from patients undergoing RYGB (n = 22) and non-obese control participants (n = 20) at baseline and at a median of 6.5 months after surgery. Markers of systemic inflammation and glucose homeostasis were measured. Expression of pro-inflammatory genes and proto-oncogenes in the rectal mucosa was quantified using qPCR. Crypt cell proliferation state of the rectal mucosa was assessed by counting mitotic figures in whole micro-dissected crypts.ResultsAt 6.5 months post-surgery, participants had lost 29 kg body mass and showed improvements in markers of glucose homeostasis and in systemic inflammation. Expression of pro-inflammatory genes in the rectal mucosa did not increase and COX-1 expression fell significantly (P = 0.019). The mean number of mitoses per crypt decreased from 6.5 to 4.3 (P = 0.028) after RYGB.ConclusionRYGB in obese adults led to lower rectal crypt cell proliferation, reduced systemic and mucosal markers of inflammation and improvements in glucose regulation. These consistent findings of reduced markers of tumourigenic potential suggest that surgically induced weight loss may lower CRC risk.
Highlights
Obesity is a well-established risk factor for colorectal cancer (CRC) [1]
The obese and non-obese groups were well matched with no differences in age, sex, NSAID use and previous cholecystectomy rates
Our main findings were a 34% decrease in the mean number of mitoses per crypt and a contraction of the crypt proliferative compartment at 6.5 months after Roux-en-Y gastric bypass (RYGB). These changes were associated with dramatic improvements in systemic markers of glucose homeostasis and inflammation
Summary
Obesity is a well-established risk factor for colorectal cancer (CRC) [1]. Obese individuals are estimated to have a 33% higher risk of CRC compared with those with a normal body mass index (BMI) [2]. Excess adiposity is a significant risk factor for colorectal adenoma (CRA) [3], suggesting that it plays a role in the early stages of CRC development. There are several plausible mechanisms through which body fatness could increase CRC risk, which have been reviewed in detail elsewhere [4]. Obese individuals exhibit a state of chronic low-grade systemic inflammation [5]. Chronic inflammation of the colorectal mucosa in individuals with
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