Serum zonulin and colorectal cancer risk

Abstract

Intestinal permeability has been related to colorectal cancer (CRC) development. Zonulin, a protein able to regulate tight junction function and intestinal permeability, emerges as a promising marker to elucidate the contribution of bacterial translocation in CRC. An Italian case-control study included 77 CRC cases, 72 intestinal adenoma and 76 healthy controls (for a total of 148 tumor-free subjects), aged 20-85. Serum zonulin levels were quantified by ELISA kit and blood 16S rRNA gene copies by DNA extraction and polymerase chain reaction. We applied logistic regression models adjusted for center, sex, age and education. There was a positive association between zonulin and CRC risk. The odds ratio (OR) of CRC for the highest versus lowest tertile of zonulin as compared to tumor-free subjects was 2.36 (95% confidence interval, 1.14-4.86). The ORs were similar in colon and rectal cancers. The OR of colon cancer for the highest versus lowest levels of both zonulin and 16S rRNA gene copies was 4.55.Circulating levels of zonulin were higher in CRC patients compared to tumor-free controls supporting the hypothesis of an interplay of gut barrier dysfunction and bacterial translocation in colorectal carcinogenesis. Zonulin may interact with 16S rRNA gene copies and serve as a further biomarker in the evaluation of CRC diagnosis.

Fig. 1

Plot^a of serum zonulin distribution among colorectal cancer (CRC) cases (n = 77), intestinal adenoma (IA) (n = 72) and healthy controls (n = 76). ^aLines indicate first, second and third quartiles.

Fig. 2

Odds ratios^a (ORs) of colorectal cancer (CRC) and 95% confidence intervals (CIs) for the highest versus the lowest zonulin tertile by strata of sex, age and education among 77 CRC and 148 tumor-free subjects. Italy 2017–2019. ^a Estimated from logistic regression model adjusted for study center, sex, age, education.