The Effect of Low Doses of Acetylsalicylic Acid on the Occurrence of Rectal Aberrant Crypt Foci.

Background and Objectives: Aberrant crypt foci (ACF) are one of the earliest putative preneoplastic and, in some cases, neoplastic lesions in human colons. Many studies have confirmed the reduction of ACFs and colorectal adenomas after treatment with acetylsalicylic acid (ASA) commonly referred to as ASA; however, the minimum effective dose of ASA and the duration of use has not been fully elucidated. The objective of our study was to assess the significance of low dose ASA (75-mg internally once daily) to study the chemopreventive effect of ASA in ACF and adenomas development in patients taking this drug for a minimum period of 10 years. Materials and Methods: Colonoscopy, combined with rectal mucosa staining with 0.25% methylene blue, was performed on 131 patients. The number of rectal ACF in the colon was divided into three groups: ACF < 5; ACF 5−10; and ACF > 10. Patients were divided into two groups: the "With ASA" group (the study group subjects taking ASA 75-mg daily for 10 years); and "Without ASA" group (control group subjects not taking ASA chronically). The incidence of different types of rectal ACF and colorectal polyps in both groups of subjects was analysed and ascertained. Results: Normal ACF was found in 12.3% in the study group vs. 87.7% control group, hyperplastic 22.4% vs. 77.6%, dysplastic 25% vs. 75%, mixed 0% vs. 100%. Treatment with ASA affects the occurrence of colorectal adenomas. The amount of dysplastic ACFs was lower in the study group than in the control group. The increase in dysplastic ACFs decreases with age in both groups, with the increase greater in those not taking ASA. Conclusions: Patients who take persistent, chronic (>10 years) low doses of ASA have a lower total number of all types of rectal ACFs and adenomas compared to the control group.

Occurrence of colorectal aberrant crypt foci depending on age and dietary patterns of patients.

BACKGROUND: Aberrant crypt foci (ACF) are commonly considered the early pre-cancerous lesions that can progress to colorectal cancer (CRC). The available literature data reveal that age, dietary factors and lifestyle can affect the development of several dozen percentages of malignant tumours, including CRC. In the present study, an attempt was made to assess the incidence and growth dynamics of ACF and to determine whether the type of diet affected the development and number of AFC. METHODS: Colonoscopy combined with rectal mucosa staining with 0.25% methylene blue was performed in 131 patients. On the day of examination, each patient completed a questionnaire regarding epidemiological data. According to their numbers, colorectal ACF were divided into three groups. The findings were analysed statistically. The Student's t test and the U test were applied in order to determine the significance of differences of means and frequency of events in both groups. Statistica 7.1 and Excel 2010 were used. RESULTS: The single ACF occur in the youngest individuals (ACF < 5). Since the age of 38 years, the number of ACF gradually increases to show a decreasing tendency since the age of 60 years. The number of 5 < ACF < 10 occurs slightly later, since the age of 50 years, and dynamically increases reaching the maximum at the age of 62 years, subsequently the increase is proportional. ACF > 10 occur at a more advanced age (55 years) and their number gradually increases with age. The maximum number is observed at the age of 77 years. In individuals not using high-fibre diets and with high intake of red meat, the probability of higher numbers of ACF increases. The probability of higher numbers of ACF (5 < ACF10) was observed in patients with colon diverticula. In patients with higher BMI, the number of ACF is higher. CONCLUSION: Age significantly affects the number of colorectal ACF. The types of foods consumed can considerably increase the risk of colorectal ACF, which is particularly visible in individuals who do not regularly use high-fibre diets, those obese and with colon diverticula.

The influence of chronic L-carnitine supplementation on the formation of preneoplastic and atherosclerotic lesions in the colon and aorta of male F344 rats.

L-Carnitine, a key component of fatty acid oxidation, is nowadays being extensively used as a nutritional supplement with allegedly "fat burning" and performance-enhancing properties, although to date there are no conclusive data supporting these claims. Furthermore, there is an inverse relationship between exogenous supplementation and bioavailability, i.e., fairly high oral doses are not fully absorbed and thus a significant amount of carnitine remains in the gut. Human and rat enterobacteria can degrade unabsorbed L-carnitine to trimethylamine or trimethylamine-N-oxide, which, under certain conditions, may be transformed to the known carcinogen N-nitrosodimethylamine. Recent findings indicate that trimethylamine-N-oxide might also be involved in the development of atherosclerotic lesions. We therefore investigated whether a 1-year administration of different L-carnitine concentrations (0, 1, 2 and 5 g/l) via drinking water leads to an increased incidence of preneoplastic lesions (so-called aberrant crypt foci) in the colon of Fischer 344 rats as well as to the appearance of atherosclerotic lesions in the aorta of these animals. No significant difference between the test groups regarding the formation of lesions in the colon and aorta of the rats was observed, suggesting that, under the given experimental conditions, L-carnitine up to a concentration of 5 g/l in the drinking water does not have adverse effects on the gastrointestinal and vascular system of Fischer 344 rats.

Predictive value of rectal aberrant crypt foci for intraepithelial neoplasia in ulcerative colitis - a cross-sectional study.

BACKGROUND: Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). Aberrant crypt foci (ACF) are important biomarkers of sporadic CRC risk. Their correlation with the risk of intraepithelial neoplasia (IN) in UC remains unclear. AIMS: To assess whether ACF are a risk factor for IN in long-standing UC and to investigate any correlation between the clinico-epidemiological characteristics and prevalence/number of ACF in these patients. METHODS: Seventy-six patients with long-standing UC were prospectively screened by colonoscopy with chromoendoscopy-guided endomicroscopy. ACF were sought in the lower rectum. RESULTS: Eight INs were detected in seven (9.2%) patients. The ACF prevalence and mean number were 60.5% and 2.4 ± 2.8, respectively. The number of ACF was independently associated with the risk of having IN (odds ratio = 1.338; 95% confidence interval 1.030-1.738). ACF number revealed a good calibration (area under the receiver operating characteristic curve = 0.829) and discriminative ability (p = 0.205, Hosmer-Lemeshow test) for the prediction of synchronous IN. Patients with ≥3 ACF have a significantly higher prevalence of IN than patients with <3 ACF (22.6% vs. 0%, p = 0.001). Using this cut-off value, the performance of ACF in predicting the presence of IN was as follows: sensitivity = 100%, specificity = 65.2%, positive predictive value = 22.6%, and negative predictive value = 100%. Age >40 years, family history of CRC, and increased body mass index (BMI) were associated with a significantly higher number of ACF. CONCLUSION: Long-standing UC patients with ≥3 ACF have a significantly higher likelihood of having IN. Age >40 years, family history of CRC, and increased BMI have significant positive associations with the number of ACF.

Effect of prebiotics on biomarkers of colorectal cancer in humans: a systematic review.

Prebiotics may prevent colorectal cancer (CRC) development in humans by modifying the composition or activity of the colorectal microflora. Epidemiologic and animal studies have shown a reduction in CRC or CRC biomarkers after the administration of prebiotics. Studies using indirect chemical biomarkers of CRC in humans, however, gave mixed results. Recently, human studies measuring direct physical indices of CRC risk after prebiotic consumption have been published. The purpose of this review is to summarize those studies to provide recommendations for the use of prebiotics in CRC risk reduction. A PubMed search was conducted, revealing nine studies. One tested lactulose, two evaluated a blend of oligofructose and inulin, and six measured resistant starch. Lactulose reduced adenoma recurrence, while resistant starch had no effect on adenoma or CRC development. Crypt mitotic location, gene expression, and DNA methylation were somewhat improved after resistant starch consumption. No changes in cell proliferation and apoptosis, crypt morphology, or aberrant crypt foci were found. More human studies measuring physical changes to the gut are needed.

High-fat diet alters gene expression in the liver and colon: links to increased development of aberrant crypt foci.

BACKGROUND: Obesity is associated with an increased risk of colon cancer. High-fat diets that lead to obesity may be a contributing factor, but the mechanisms are unknown. AIMS: This study examines susceptibility to azoxymethane (AOM)-induced precancerous lesions in mice in response to consumption of either a low or a high-fat diet and associated molecular changes in the liver and colon. METHODS: Gene markers of xenobiotic metabolism, leptin-regulated inflammatory cytokines and proliferation were assessed in liver and colon in response to high-fat feeding to determine links with increased sensitivity to AOM. RESULTS: High-fat feeding increased development of AOM-induced precancerous lesions and was associated with increased CYP2E1 gene expression in the liver, but not the colon. Leptin receptors and the colon stem cell marker (Lgr5) were down-regulated in the proximal colon, with a corresponding up-regulation of the inflammatory cytokine (IL6) in response to high-fat feeding. Notably in the distal colon, where aberrant crypt foci develop in response to AOM, the proliferative stem cell marker, Lgr5, was significantly up-regulated with high-fat feeding. CONCLUSIONS: The current study provides evidence that high-fat diets can alter regulation of molecular markers of xenobiotic metabolism that may expose the colon to carcinogens, in parallel with activation of ß-catenin-regulated targets regulating colon epithelial cells. High-fat diets associated with obesity may alter multiple molecular factors that act synergistically to increase the risk of colon cancer associated with obesity.

Investigation of the prevalence and number of aberrant crypt foci associated with human colorectal neoplasm.

BACKGROUND: Aberrant crypt foci (ACF) are considered to be useful as surrogate biomarker for colorectal cancer (CRC), but the biological significance of ACF remains controversial. We attempted to investigate the relationship between the presence of ACF and human colorectal carcinogenesis using a relatively large sample size. METHODS: We carried out high-magnification chromoscopic colonoscopy to identify ACFs in 861 subjects undergoing a diagnostic endoscopy at the Yokohama City University Hospital. The present study compared the prevalence and number of ACFs in three subject groups (normal subjects, adenoma cases, and CRC cases). The correlations between the demographic and behavioral characteristics of the subjects and the prevalence of ACFs were also assessed. RESULTS: The prevalence of ACF was 64%, 88%, and 95%, and the mean number of ACF was 3.6, 6.2, and 10.1, in normal subjects, adenoma cases, and CRC cases, respectively. When differences in the prevalence and number of ACFs among age- and sex-stratified subject groups were examined, significant stepwise increments from normal subjects to adenoma cases to CRC cases were apparent (P < 0.001). Moreover, an age- and sex-adjusted multiple logistic regression analysis revealed that smoking and alcohol habits had a synergistic effect, increasing the prevalence of ACFs as well as the risk of CRC (P < 0.001). CONCLUSIONS: These results suggested that ACF may serve as a reliable surrogate biomarker for human colorectal carcinogenesis. IMPACT: The use of ACF as an endpoint may enable the size, duration, and cost of CRC chemoprevention studies to be reduced.

Sex differences in associations between psychosocial factors and aberrant crypt foci among patients at risk for colon cancer.

BACKGROUND: Psychosocial factors may impact cancer risk but sex differences in this domain are understudied. Examining psychosocial factors, such as depression and social support, among colon cancer patients allows for a unique opportunity to study sex differences in the association between psychosocial factors and colon cancer risk in this population. OBJECTIVE: The primary aim of this study was to evaluate sex differences in the association between key psychosocial factors and aberrant crypt foci (ACF), a putative biomarker of colon cancer risk. We hypothesized that higher levels of depression in women and lower levels of social support in men were associated with greater numbers of ACF among individuals at heightened risk for colon cancer. METHODS: Participants were self-referred or referred by physicians for routine colonoscopy. Within 2 weeks before colonoscopy, participants completed standardized measures assessing psychosocial factors. At colonoscopy, individuals were examined for ACF frequency in the distal 20 cm of the colorectum. Regression ß weights were used to examine the association between the psychosocial factors and ACF. RESULTS: A total of 93 individuals (51% women, 49% men) consented to the study. Among women, higher levels of depressive symptoms were associated with greater numbers of ACF; among men, lower levels of social support were associated with greater numbers of ACF. CONCLUSIONS: These results suggest that although colon cancer affects men and women equally with regard to morbidity and mortality rates, there were important sex differences in how psychosocial variables were related to colon cancer risk. Psychosocial interventions aimed at targeting these types of factors are warranted but need to consider the role of sex.