Abstract
Excessive alcohol consumption is a risk factor associated with colorectal cancer; however, some epidemiological studies have reported that moderate alcohol consumption may not contribute additional risk or may provide a protective effect reducing colorectal cancer risk. Prior research highlights the importance of proliferation, differentiation, and apoptosis as parameters to consider when evaluating colonic cell growth and tumorigenesis. The present study investigated whether chronic low-to-moderate ethanol consumption altered these parameters of colonic cell growth and expression of related genes. Twenty-four nondeprived young adult (109 days old) and 24 nondeprived middle-aged (420 days old) Wistar rats were randomly assigned to an ethanol-exposed or a water control group (n = 12/group). The ethanol group was provided voluntary access to a 20% v/v ethanol solution on alternate days for 13 weeks. Colon tissues were collected for quantitative immunohistochemical analyses of cell proliferation, differentiation and apoptosis using Ki-67, goblet cell and TUNEL, respectively. Gene expression of cyclin D1 (Ccnd1), Cdk2, Cdk4, p21waf1/cip1 (Cdkn1a), E-cadherin (Cdh1) and p53 were determined by quantitative real-time polymerase chain reaction in colonic scraped mucosa. Ethanol treatment resulted in a lower cell proliferation index and proliferative zone, and lower Cdk2 expression in both age groups, as well as trends toward lower Ccnd1 and higher Cdkn1a expression. Cell differentiation was modestly but significantly reduced by ethanol treatment only in older animals. Overall, older rats showed decreases in apoptosis and gene expression of Cdk4, Cdh1, and p53 compared to younger rats, but there was no observed effect of ethanol exposure on these measures. These findings suggest that low-to-moderate ethanol consumption improves at least one notable parameter in colonic tumorigenesis (cell proliferation) and associated gene expression regardless of age, however, selectively decreased cell differentiation among older subjects.
Highlights
According to the American Cancer Society, colorectal cancer (CRC) is ranked third in diagnosis and mortality for both men and women, and ranked second in mortality when men and women are combined, with an estimated 147,950 new cases and 53,200 deaths in 2020 [1]
The present study examined the effects of chronic voluntary low-to-moderate ethanol consumption on several measures of colonic cell growth, including cell proliferation, differentiation, and apoptosis, and whether effects of ethanol on these parameters vary as a function of age
The results of this study contribute to a currently limited literature on the effects of low-tomoderate ethanol intake on several parameters of colonic cell growth and associated gene expression. These findings indicate that low-to-moderate ethanol treatment improved at least one parameter of colonic tumorigenesis, producing a decrease in cell proliferation
Summary
According to the American Cancer Society, colorectal cancer (CRC) is ranked third in diagnosis and mortality for both men and women, and ranked second in mortality when men and women are combined, with an estimated 147,950 new cases and 53,200 deaths in 2020 [1]. Excessive alcohol consumption is a known risk factor for CRC development, existing data indicate that lower doses may not have the same impact on risk level. Other reports have indicated a nonlinear relationship between ethanol dose and development of CRC, with either no association [5] or protective effects [6,7] at lower doses, while excessive consumption increased risk [7]. These effects may importantly interact with diet, additional risk factors (e.g., obesity), and genetic susceptibility [8]. Data addressing the impact of low-to-moderate ethanol consumption on CRC risk in controlled experimental models is currently very limited
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