Afshar Sorena, Malcomson Fiona, Kelly Seamus B, Seymour Keith, Woodcock Sean, Mathers John C
Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle on Tyne, NE4 5PL, UK.
Northumbria Healthcare NHS Foundation Trust, North Tyneside General Hospital, Rake Lane, North Shields, NE29 8NH, UK.
Obes Surg. 2018 Apr;28(4):945-954. doi: 10.1007/s11695-017-2953-6.
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.
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.
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.
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.
体重减轻对肥胖相关结直肠癌（CRC）风险的影响尚不明确。先前的研究表明，Roux-en-Y胃旁路术（RYGB）可能对CRC风险产生意外的不利影响。本研究旨在调查RYGB对CRC风险生物标志物的影响。
在基线以及术后6.5个月（中位数）时，从接受RYGB手术的患者（n = 22）和非肥胖对照参与者（n = 20）获取直肠黏膜活检组织和血液。测量全身炎症和葡萄糖稳态的标志物。使用qPCR定量直肠黏膜中促炎基因和原癌基因的表达。通过计数全微分离隐窝中的有丝分裂图像评估直肠黏膜的隐窝细胞增殖状态。
术后6.5个月，参与者体重减轻了29 kg，葡萄糖稳态标志物和全身炎症均有所改善。直肠黏膜中促炎基因的表达未增加，COX-1表达显著下降（P = 0.019）。RYGB术后每个隐窝的平均有丝分裂数从6.5降至4.3（P = 0.028）。
肥胖成年人接受RYGB手术可导致直肠隐窝细胞增殖降低、全身和黏膜炎症标志物减少以及葡萄糖调节改善。这些一致的肿瘤发生潜能标志物降低的结果表明，手术诱导的体重减轻可能会降低CRC风险。
