Biomarkers of Colorectal Cancer Risk Decrease 6 months After Roux-en-Y Gastric Bypass Surgery

Abstract

Purpose: The 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 methods: Rectal 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.

Results: At 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.

Conclusion: RYGB 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.

Keywords: Bariatric surgery; Colorectal cancer; Gastric bypass; Obesity; Proliferation.

Fig. 1

Flow of participants through the study

Fig. 2

Rectal mucosal crypt cell proliferation status in non-obese control participants and in obese participants pre- and post-RYGB surgery. a Mean total number of mitoses per crypt. b Percentage of mitoses in the upper half of the crypt. c Mean crypt area. Dark circles represent mean for the group and error bars represent standard error. Independent sample t test used to compare non-obese control and obese pre-surgery participants. Paired sample t test used to compare obese participants pre- and post-surgery (*p < 0.05)