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ACCEPTED: COLON

Serum Levels of Zonulin and Risk of Colorectal Tumor: A Pilot Case Control Study

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Gurwara, Shawn MD; Chen, Liang MD, MS; Plew, Sarah BS; Kourkoumpetis, Themis MD; Rosen, Daniel MD; White, Donna PhD, MPH; Graham, David Y. MD, MACG; El-Serag, Hashem MD, MPH; Jiao, Li MD, MS, PhD

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American Journal of Gastroenterology: October 2018 - Volume 113 - Issue - p S69
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Introduction: Increased intestinal permeability has been associated with colorectal carcinogenesis. Zonulin is one of the hormones in humans known to regulate intestinal permeability. We examined the association between serum levels of zonulin and risk of colorectal polyps, adenomas or advanced adenomas. We also examined the association between zonulin and obesity.

Methods: In a case-control study, we enrolled patients who underwent colonoscopies. We included 87 controls who were found to have normal mucosa. Our three case groups included 27 with small polyps, 78 with adenomas, and 47 with advanced adenomas. Cases and controls were individually matched by age, sex, race/ethnicity, and time of blood draw (± 3 months). Information on age, ethnicity, sex, BMI, smoking, and comorbidities was collected from all participants during the enrollment interview. We collected fasting blood from the patients before they underwent colonoscopies. We used the ALPCO ELISA kit to measure serum levels of zonulin (ng/ml). We used paired student t-test to compare zonulin levels across groups. Conditional logistic regression was used to estimate multivariable odds ratio and its 95% confidence interval for risk of colorectal tumors using low or high zonulin levels (median among controls as the cut-off point).

Results: The study participants were 50-75 years old, 75% were White and 8 were women. The distribution of age, sex, ethnicity, smoking status, and BMI were equivalent between controls and each case group. The levels of zonulin (mean: 3.00 ng/ml, standard deviation (SD): 1.22) were higher among controls compared with the cases (polyps (mean: 2.79 ng/ml, SD: 0.93, P = 0.17)), non-advanced adenomas (mean: 2.93 ng/ml, SD: 1.16, P = 0.98), and advanced adenomas (mean: 2.66 ng/ml, SD: 1.06, P = 0.11)).. The multivariate logistics regression analysis also showed a higher levels of zonulin was associated with non-significantly reduced risk of polyps (OR = 0.24, 95% CI: 0.02-2.51), non-advanced adenomas (OR = 0.57, 95% CI: 0.22-1.48), and advanced adenomas (OR = 1.01, 95% 0.36-2.88). Among 87 polyp-free controls, the levels of zonulin was higher among non-obese individuals than obese individuals (mean: 3.14 ng/ml; SD: 1.37 versus 2.88 ng/ml (SD: 1.07), P = 0.32).

Conclusion: We found no association between zonulin levels and risk of colorectal tumors or obesity. A larger scale study is worth confirming the trend of inverse association between circulating zonulin levels and risk of colorectal adenoma and obesity.

© The American College of Gastroenterology 2018. All Rights Reserved.