Distal Colon Adenoma Research Articles

Colocalization with MMP-7 in the Distal Colon is Crucial for Syndecan-2 Shedding in Dextran Sulfate Sodium-Induced Colitis Mice.

IntroductionSyndecan-2 expression is elevated during chronic inflammation and cancer development, and its shedding is observed in cancer patients. However, it remained unknown whether inflammation triggers syndecan-2 shedding.MethodsThe colitis model was produced in C57BL/6 mice by oral administration of 2–3% dextran sulfate sodium (DSS) in the drinking water. Syndecan-2 and MMP-7 expression levels in tissues and cells were detected by real-time PCR, Western blotting, and immunohistochemistry. Shed syndecan-2 levels were detected by slot blotting. For tissue culture, colon tissues were divided into proximal, transverse, and distal parts, and incubated in culture media.ResultsIn C57BL/6 mice with DSS-induced colitis, syndecan-2 shedding began to increase after week 12 of chronic inflammation and continued to increase at week 15. The level of shed syndecan-2 correlated with the colocalization of syndecan-2 and MMP-7 in distal colon tissues. The mRNA expression of IL-6 was increased specifically in trans-distal colon tissues from weeks 9 to 15. IL-6 induced syndecan-2 expression and shedding and MMP-7 expression in ex vivo-cultured distal colon tissues and adenoma cell lines derived from the distal colon. IL-6 treatment induced STAT3 phosphorylation and MMP-7 expression in DLD-1 cells. The application of MMP-7 to ex vivo-cultured colon tissues increased the shedding of syndecan-2 to the culture medium.ConclusionOur findings suggest that chronic inflammation induces syndecan-2 shedding via the site-specific colocalization of syndecan-2 with MMP-7 in the distal colon.

Bacterial-Driven Inflammation and Mutant BRAF Expression Combine to Promote Murine Colon Tumorigenesis That Is Sensitive to Immune Checkpoint Therapy.

Colorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced by inflammation, mutagens, and/or microbiota. Colorectal cancers with activating mutations in BRAF are associated with distinct clinical characteristics, although the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (MinApcΔ716/+) enterotoxigenic Bacteroides fragilis (ETBF) murine model is characterized by IL17-dependent, distal colon adenomas. Herein, we report that the addition of the BRAF V600E mutation to this model results in the emergence of a distinct locus of midcolon tumors. In ETBF-colonized BRAF V600E Lgr5 CreMin (BLM) mice, tumors have similarities to human BRAF V600E tumors, including histology, CpG island DNA hypermethylation, and immune signatures. In comparison to Min ETBF tumors, BLM ETBF tumors are infiltrated by CD8+ T cells, express IFNγ signatures, and are sensitive to anti-PD-L1 treatment. These results provide direct evidence for critical roles of host genetic and microbiota interactions in colorectal cancer pathogenesis and sensitivity to immunotherapy. SIGNIFICANCE: Colorectal cancers with BRAF mutations have distinct characteristics. We present evidence of specific colorectal cancer gene-microbial interactions in which colonization with toxigenic bacteria drives tumorigenesis in BRAF V600E Lgr5 CreMin mice, wherein tumors phenocopy aspects of human BRAF-mutated tumors and have a distinct IFNγ-dominant immune microenvironment uniquely responsive to immune checkpoint blockade.This article is highlighted in the In This Issue feature, p. 1601.

Dairy intake during adolescence and risk of colorectal adenoma later in life

BackgroundHigher dairy intake during adulthood has been associated with lower colorectal cancer risk. As colorectal carcinogenesis spans several decades, we hypothesised that higher dairy intake during adolescence is associated with lower risk of colorectal adenoma, a colorectal cancer precursor.MethodsIn 27,196 females from the Nurses’ Health Study 2, aged 25–42 years at recruitment (1989), who had completed a validated high school diet questionnaire in 1998 and undergone at least one lower bowel endoscopy between 1998 and 2011, logistic regression for clustered data was used to calculate odds ratios (ORs) and 95% confidence intervals (CI).ResultsColorectal adenomas were diagnosed in 2239 women. Dairy consumption during adolescence was not associated with colorectal adenoma risk (OR highest vs. lowest [≥4 vs. ≤1.42 servings/day] quintile [95% CI] 0.94 [0.80, 1.11]). By anatomical site, higher adolescent dairy intake was associated with lower rectal (0.63 [0.42, 0.95]), but not proximal (1.01 [0.80, 1.28]) or distal (0.97 [0.76, 1.24]) colon adenoma risk. An inverse association was observed with histologically advanced (0.72 [0.51, 1.00]) but not non-advanced (1.07 [0.86, 1.33]) adenoma.ConclusionsIn this large cohort of younger women, higher adolescent dairy intake was associated with lower rectal and advanced adenoma risk later in life.

Analysis of proliferation and apoptosis, MUC-1 and Cdx-2 expression in distal colonic polyps

Background. The universal molecular characteristics of malignancy are activation of cell proliferation and inactivation of apoptotic cell death. Besides genes-regulators of the processes other molecules are involved, including mucins and Cdx-2. Aim . To conduct comparative and correlation analysis of indexes of immunohistochemical expression of Ki-67, p53, caspase-3, as well as MUC-1 and Cdx-2 in distal colonic polyps. Methods. Pathohistological and immunohistochemical studies of biopsies of adenomas and hyperplastic polyps from 40 patients were carried out. Results. Distal colonic polyps are characterized by medium proliferation level: the median of Ki-67 expression for hyperplastic polyps is 42,20 (35,27; 52,38) %, while the median for adenomas is 65,39 (52,28; 76,23) % (р˂0,05). The polyps are characterized by low p53 expression levels: the median of the marker expression for hyperplastic polyps is 1,53 (1,17; 3,16) %, for adenomas – 9,15 (8,26; 12,39) % (р˂0,05). The studied polyps are characterized by low apoptosis levels: the median of caspase-3 expression for hyperplastic polyps is 33,78 (30,28; 42,34) CUOD, for adenomas – 22,19 (16,84; 40,51) CUOD (р˂0,05). Distal colonic polyps are characterized by medium MUC-1 and Cdx-2 expression levels: the medians of the markers expression for hyperplastic polyps are 62,13 (34,20; 71,85) CUOD and 71,81 (62,36; 77,77) CUOD, for adenomas – 80,25 (52,14; 95,21) CUOD and 95,14 (81,19; 112,17) CUOD, respectively (р˂0,05). The correlation analysis revealed several correlations: reverse medium strength correlation between p53 and caspase-3 expression levels (r = -0,57, р˂0,05), direct medium strength correlation between caspase-3 and MUC-1 expression levels (r = 0,52, p˂0,05) take place in hyperplastic polyps, whereas reverse strong correlation between caspase-3 and MUC-1 expression levels 1 (r = -0,88, p˂0,05) takes place in adenomas. Conclusions. Distal colonic adenomas differ by higher proliferation and p53 expression levels, comparing to hyperplastic polyps, and by lower apoptosis level that is associated with higher MUC-1 expression level as well. Hyperplastic polyps differ by higher apoptosis level that is associated with lower MUC-1 expression level. Cdx-2 expression increases on benign adenoma stage and does not correlate with proliferation and apoptosis indexes.

Distal colonic polyps: immunohistochemical study of proliferation and apoptosis

Background. It’s well known that colonic polyps can be precursors of colorectal cancer. But exact immunohistochemical parameters, including proliferation and apoptosis levels of polyps’ cells, that may have prognostic value, still not known. Objective. To study the features of immunohistochemical expression of proliferation and apoptosis markers by distal colonic polyps’ cells. Methods. Pathomorphological and immunohistochemical studies of biopsies of distal colonic polyps from 30 patients (the age ranged from 41 to 83 years) were carried out. Results. Distal colonic polyps are characterized by the medium proliferation level of epithelial cells [Me=62.40% (48.65; 76.23) for adenomas, Me=26.23% (22.19; 48.88) for hyperplastic polyps], the low proliferation level of stromal cells [Me=2.94% (1.23; 4.35) for adenomas, Me=1.18% (1.10; 1.86) for hyperplastic polyps], the low p53 expression level of epithelial and stromal cells [Me=2.39% (1.58; 8.26) and Me=1.23% (0.72; 1.49) for adenomas’ cells, Me=0,00% (0,00; 1,47) and Me=0,00% (0,00; 0,05) for hyperplastic polyps’ cells], and also by the low apoptosis level of epithelial and stromal cells [Me=31.84CUOD (19.53; 42.34) and Me=43.87CUOD (25.47; 73.09) for adenomas, Me=16.99CUOD (11.86; 39.85) and Me=28.64CUOD (19.20; 30.71) for hyperplastic polyps]. There are direct correlations between the expression levels of proliferation and apoptosis markers and also the dysplasia grade of the distal colonic adenomas: between the Ki-67 expression levels of epithelial and stromal cells and also the dysplasia grade (γ=0.65 and γ=0.70, respectively), between the p53 expression level of epithelial cells and the dysplasia grade (γ=0.53), between the caspase-3 expression levels of epithelial and stromal cells and also the dysplasia grade (γ=0.80 and γ=0.63, respectively). Moreover, there are direct correlations between the expression levels of proliferation and apoptosis markers of distal colonic polyps’ epitheliocytes: between the Ki-67 and p53 expression levels (r=0.71 for adenomas, r=0.79 for hyperplastic polyps), between the Ki-67 and caspase-3 expression levels (r=0.61 for adenomas), between the p53 and caspase-3 expression levels (r=0.59 for adenomas, r=0.79 for hyperplastic polyps). Conclusion. These data indicate the close association between the processes of proliferation, accumulation of p53 protein, and apoptosis of the distal colonic polyps’ cells.

Prevalence and characteristics of colonic adenoma in mainland China.

Background and aimTo investigate the prevalence and characteristics of colonic adenoma and advanced colonic adenoma in a large group of patients in mainland China.Materials and methodsWe conducted a cross-sectional study on patients who had undergone colonoscopy examination in a university hospital in mainland China. Colonic adenomas and advanced adenomas were recorded.ResultsThe prevalence of polyps, adenoma, and advanced adenoma was 23.9%, 13.3%, and 3.5%, respectively. Age and sex were independent risk factors for the prevalence of adenoma and advanced adenoma. Polyp size was associated with an increased risk of both colonic adenoma (OR 1.50, 95% CI 1.44–1.56) and advanced adenoma (OR 2.78, 95% CI 2.55–3.03) after sex and age adjustment. Proximal colon polyps were a risk factor for adenoma (OR 1.41, 95% CI 1.20–1.66) and also associated with a significant reduction (44%) in risk of advanced adenoma (OR 0.56, 95% CI 0.36–0.86) compared to distal colon adenoma after sex and age adjustment. A screening indication was associated with a statistically significant decrease in the odds of prevalence of adenoma (OR 0.90, 95% CI 0.81–0.99) and advanced adenoma (OR 0.72, 95% CI 0.59–0.88) compared to a no-screening indication.ConclusionThe overall prevalence of adenoma was low in mainland China. It exhibited a varied pattern with respect to age and sex. Polyp size was a risk factor for both colonic adenoma and its transition to advanced adenoma. Proximal colon polyps were a risk factor for adenoma, but a protective factor for advanced adenoma compared to distal colon adenoma.

Coffee intake and the risk of colorectal adenoma: The colorectal adenoma study in Tokyo

Coffee is a commonly consumed beverage which contains several potential anticarcinogenic and chemopreventive compounds, and has been hypothesized to have protective effects in colorectal neoplasia. However, the limited available data on coffee consumption in relation to colorectal adenoma (CRA), a precursor lesion to most colorectal cancers, remain largely inconsistent. In this study, we evaluated the association of coffee intake with the risk of CRA in a middle-aged Japanese population. Study subjects were selected from examinees who underwent total colonoscopy as part of a cancer screening program and responded to self-administered dietary and lifestyle questionnaires. A total of 738 patients with adenoma and 697 controls were included in the study. Coffee intake was assessed with a food frequency questionnaire, and divided into quartiles based on the distribution among controls. Unconditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) of CRA, with adjustment for potential confounding factors. High coffee consumption was associated with a reduced risk of CRA, with a multivariate-adjusted OR for the highest versus lowest quartile of coffee intake of 0.67 (95% CI = 0.48-0.93; ptrend = 0.02). The inverse association of coffee intake was limited to proximal (OR = 0.64; 95%CI = 0.44-0.95; ptrend = 0.04) and distal colon adenoma (OR = 0.62; 95%CI = 0.39-0.99; ptrend = 0.06), and appeared to be more evident with small (OR = 0.68; 95%CI = 0.49-0.96; ptrend = 0.04) and single adenomas (OR = 0.65; 95%CI = 0.44-0.95; ptrend = 0.02). Green tea intake was not found to be associated with CRA risk. This study provides support for the protective effect of coffee drinking on colon adenomas, a precursor of colon cancer.

Ethnic disparities in the risk of colorectal adenomas associated with aspirin and statin use: a retrospective multiethnic study.

Although data on the inverse association between colorectal adenomas (CRA) and daily aspirin or statin therapy exists in white and black patients, scarce data exists on these associations in the Hispanic population. With a rapidly increasing Hispanic population in the United States, defining the association in Hispanics is crucial. The study sample included 1,843 consecutive patients who underwent a colonoscopy (screening or diagnostic) from 2009 to 2011 at a community hospital in East Meadow, New York. Data was then extracted from patient charts regarding aspirin and/or statin use. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were calculated to assess the association between colonoscopy findings and aspirin, statin, or aspirin/statin use. In our total population including all races, aspirin user had an increased risk for having two or more adenomas (OR =1.73, 95% CI: 1.00, 2.99, P=0.05) and presence of an adenoma in the proximal colon (OR =1.66, 95% CI: 1.07, 2.58, P=0.02). In the total study population, those who used both statin and aspirin had an increased risk for having two or more adenomas (OR =2.56, 95% CI: 1.21, 5.39, P=0.01). In the Hispanic population, users of both medications had an increased risk for having two or more adenomas (OR =19.04, 95% CI: 1.30, 280.09, P=0.03), adenoma present in the distal colon (OR =5.75, 95% CI: 1.64, 20.21, P=0.01) and largest adenoma in distal colon (OR =5.75, 95% CI: 1.64, 20.21, P=0.01). Aspirin use and aspirin/statin use was associated with abnormal colonoscopy findings, particularly in the Hispanic population. These findings may be due to environmental factors such as dietary, colonic flora, or genetic susceptibility. The findings warrant further investigational research, particularly in Hispanics.

The relationship between proximal and distal colonic adenomas

Because the relationship between distal and proximal colonic findings remains uncertain, controversy exists over whether proctosigmoidoscopy or colonoscopy is more suitable for colorectal cancer (CRC) screening. We aim to describe the distribution and characteristics of polyps removed in colonoscopy screening. A prospective registry of a colonoscopy-based CRC screening program was developed on asymptomatic individuals over 50 years. All polyps were removed and characterized. Polyp size and histology were noted. Adenomas were considered advanced if they measured greater than 10 mm or were tubulovillous, villous, or malignant. The prevalence of advanced proximal polyps was determined and patients were categorized according to their family history of CRC. A total of 696 individuals (418 women), aged 57.7 ± 10.3 years, were examined; 45.8% presented a colonic lesion, being adenomatous polyps in 32.7% individuals. Among these, 24.7% were advanced adenomas. Three patients (0.6%) presented invasive CRC. There were no significant differences with respect to sex and family history of CRC between patients with or without adenomas. Adenomas were more prevalent in individuals aged at least 65, irrespective of location (P<0.001). In 65.1% of individuals with adenomatous polyps in the right colon, there were no synchronous adenomas in the left colon (P<0.001). More adenomas were also present in the right colon of patients with no family history of CRC (P<0.001). Most patients with adenomatous polyps in the right colon showed no synchronic adenomas on the left side. Lesions on the right side would have gone undetected if the individuals undergoing CRC screening had been explored with proctosigmoidoscopy.

Physical activity and other lifestyle factors in relation to the prevalence of colorectal adenoma: a colonoscopy-based study in asymptomatic Koreans

To evaluate physical activity and other lifestyle risk factors in relation to the prevalence of colorectal adenomas in asymptomatic Koreans. A total of 1,526 asymptomatic subjects who underwent a colonoscopy were enrolled. Lifestyle factors such as physical activity and smoking data were obtained using a questionnaire. The subjects were grouped into three exposure levels by tertiles of metabolic equivalent hours per week. We evaluated the risk factors in subjects with adenomas by risk stratification (low-risk adenoma group vs. high-risk adenoma group) and by anatomic location (proximal colon, distal colon, rectum, and multiple locations). The high-risk adenoma group was defined as subjects with advanced adenomas or multiple (≥ 3) adenomas. A total of 456 participants had colorectal adenomas, and 861 had no polyps. In multivariate analyses, higher levels of physical activity were associated with a significantly decreased risk of colorectal adenomas (OR = 0.56, 95% CI 0.40-0.79). This inverse association was stronger for the risk of high-risk adenomas (OR = 0.39, 95% CI 0.21-0.73) than for low-risk adenomas (OR = 0.62, 95% CI 0.43-0.89). The negative relation of physical activity was significant for distal colon adenomas (OR = 0.54, 95% CI 0.30-0.95) and the adenomas with multiple locations (OR = 0.39, 95% CI 0.21-0.72). Increased physical activity is associated with a reduced prevalence of colorectal adenomas. The inverse association between physical activity and adenoma was stronger for the risk of advanced or multiple adenomas.

Mo1151 Increased Metabolic Score Is Associated With Synchronous Distal Colon Adenomas

Mo1151 Increased Metabolic Score Is Associated With Synchronous Distal Colon Adenomas

Helicobacter pylori infection and colorectal carcinoma: pathologic aspects.

Helicobacter pylori infection and colorectal carcinoma: pathologic aspects.

Near-infrared-labeled peptide multimer functions as phage mimic for high affinity, specific targeting of colonic adenomas in vivo (with videos)

Fluorescent-labeled peptides are being developed to improve the endoscopic detection of colonic dysplasia. To demonstrate a near-infrared peptide multimer that functions as a phage mimic for in vivo detection of colonic adenomas. A peptide multimer was synthesized by using trilysine as a dendritic wedge to mimic the presentation of peptides on phage, and all peptides, including the multimer, were fluorescent-labeled with Cy5.5. Small-animal imaging facility. ANIMAL SUBJECTS: Genetically engineered CPC;Apc mice that spontaneously develop colonic adenomas. Near-infrared-labeled AKPGYLS peptide multimer was administered topically into the distal colons of the mice, and endoscopic images of adenomas were captured. Fluorescence intensities were quantified by target-to-background (T/B) ratios, and adenoma dimensions were measured with calipers after imaging. Validation of specific peptide binding was performed on cryosectioned specimens and cells by using confocal microscopy and flow cytometry. Fluorescence T/B ratios from colonic adenomas and adjacent normal-appearing mucosa. AKP-multimer, monomer, trilysine core, and Cy5.5 resulted in mean (± SD) T/B ratios of 3.85 ± 0.25, 2.21 ± 0.13, 1.56 ± 0.12, and 1.19 ± 0.11, respectively, P < .01 on in vivo imaging. Peptide multimer showed higher contrast and greater specificity for dysplastic crypts as compared with other probes. Peptide multimer demonstrated significantly greater binding to HT29 cells on flow cytometry and fluorescence microscopy in comparison to monomer and trilysine core. A binding affinity of 6.4 nm/L and time constant of 0.1136 minutes(-1) (8.8 minutes) was measured for multimer. Only distal colonic adenomas were imaged. Peptide multimers combine strengths of multiple individual peptides to enhance binding interactions and demonstrate significantly higher specificity and affinity for tumor targets.

Meat consumption and the risk of incident distal colon and rectal adenoma

Background:Most studies of meat and colorectal adenoma have investigated prevalent events from a single screening, thus limiting our understanding of the role of meat and meat-related exposures in early colorectal carcinogenesis.Methods:Among participants in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who underwent baseline and follow-up sigmoidoscopy (n=17 072), we identified 1008 individuals with incident distal colorectal adenoma. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between meat and meat-related components and incident distal colorectal adenoma using multivariate logistic regression.Results:We observed suggestive positive associations for red meat, processed meat, haeme iron, and nitrate/nitrite with distal colorectal adenoma. Grilled meat (OR=1.56, 95% CI=1.04–2.36), well or very well-done meat (OR=1.59, 95% CI=1.05–2.43), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) (OR=1.75, 95% CI=1.17–2.64), benzo[a]pyrene (OR=1.53, 95% CI=1.06–2.20), and total mutagenic activity (OR=1.57, 95% CI=1.03–2.40) were positively associated with rectal adenoma. Total iron (diet and supplements) (OR=0.69, 95% CI=0.56–0.86) and iron from supplements (OR=0.65, 95% CI=0.44–0.97) were inversely associated with any distal colorectal adenoma.Conclusion:Our findings indicate that several meat-related components may be most relevant to early neoplasia in the rectum. In contrast, total iron and iron from supplements were inversely associated with any distal colorectal adenoma.

Metabolic syndrome, lifestyle risk factors, and distal colon adenoma: A retrospective cohort study

To investigate relationships between colorectal adenoma incidence, metabolic syndrome (MS) components and lifestyle factors. We conducted a retrospective cohort study using data from individuals who had multiple sigmoidoscopies for colon cancer at the Health Promotion Center of Ulsan University Hospital in Korea from 1998 to 2007. By multivariate analysis, the incidence of distal colon adenoma was increased by more than 1.76 times in individuals with at least one component of MS compared to those without a component of MS. After adjustment for age, gender, smoking, drinking, and physical exercise, only high body mass index (BMI) was significantly associated with the incidence of distal colon adenoma (Hazard ratio 1.66, 95% confidence interval 1.05-2.62). Our results suggest that high BMI may increase the risk of colorectal adenoma in Korean adults.

Fiber as protective factor for colon polyps

Colorectal cancer is the third leading cause of death in the United States. The change in incidence patterns observed in populations previously considered being at low risk for this disease suggests that environmental factors, including those related to diet contributes to the etiology of colorectal cancer. It has been documented that the majority of colorectal cancer arise in adenomatous polyps. Although the great majority of colon polyps are harmless, some may turn cancerous over time and as many as 30 to 40 percent of middle-age and older adults may have one or more colon polyps. It is estimated that as much as one third to one half of colon cancer risk and one fourth to one third of distal colon adenoma risk might be avoidable by modification of dietary and life-style habits. Factors that have shown the most consistent protective effect against adenomas in epidemiologic studies include, among others, dietary fiber contained in fruits, vegetables and grains. Because colonic polyps are so common in the industrialized world, prevention should play an important role. This is a cohort study to compare the association between fiber intake from fruits, vegetables and grains and the risk of physician diagnosed colon polyps among 2,818 non-Hispanic white cohort members who had undergone colonoscopy. Subjects participated in two cohort studies, the Adventist Health Study-1 (AHS-1) in 1976 and again in the Adventist Health Study-2 (AHS-2) in 2002-2005. Dietary information was obtained from the self-administered questionnaire from the AHS-1, while the outcome was assessed from the AHS-2. Logistic regression analysis was used to estimate the period risk of incident cases of polyps with adjustment for age, gender, BMI, physical activity, alcohol and meat intake. 441 incident cases of colon polyps were identified. After adjusting for age, sex, BMI, physical activity, alcohol and meat, total fiber intake was inversely associated with the risk of colon polyps (RR for highest tertile vs. lowest tertile = 0.706, 95%CI 0.506-0.986; P value= 0.04 and RR for mid tertile vs. lowest tertile = 0.808; 95%CI 0.588 - 1.112; P value= 0.19). This association showed a dose-response effect (P-value for trend= 0.0148). Analyses of various foods, showed that a protective effect of fiber contained in vegetables (RR for highest quartile vs. lowest quartile = 0.662, 95%CI 0.459 - 0.956; P value= 0.0277). Individuals with 1-<4 times/week vs. >4time/week of consumption of meat had an inverse association with colon polyps (RR= 0.592 95%CI 0.406-0.862; P value= 0.006). In this population with a high proportion of lacto-ovo-vegetarians, individuals who consume low amounts of fiber, especially fiber contained in vegetables, and high amounts of meat have higher risk of developing colon polyps. This relationship seems to have a dose-effect response.

T2040 Increased Risk of Proximal, But Not Distal Colonic Adenomas with Obesity

T2040 Increased Risk of Proximal, But Not Distal Colonic Adenomas with Obesity

Calcium and Vitamin D Intakes in Relation to Risk of Distal Colorectal Adenoma in Women

The authors examined intakes of calcium and vitamin D, and interaction with retinol, in relation to risk of adenoma of the distal colon or rectum among 48,115 US women who were free of colorectal cancer or polyps, completed a food frequency questionnaire in 1980, and underwent endoscopy by 2002. They documented 2,747 cases of adenoma (1,064 large, 1,531 small, 2,085 distal colon, and 779 rectal). Total calcium intake was weakly associated with distal colorectal adenoma risk (multivariable relative risk (RR) for extreme quintiles = 0.88, 95% confidence interval (CI): 0.74, 1.04; p(trend) = 0.06), particularly for large adenoma (RR = 0.73, 95% CI: 0.56, 0.96; p(trend) = 0.02). Total vitamin D intake was weakly associated with reduced risk of distal colorectal adenoma (RR = 0.79, 95% CI: 0.63, 0.99; p(trend) = 0.07), but more strongly with distal colon adenoma risk (RR = 0.67, 95% CI: 0.52, 0.87; p(trend) = 0.004). The combinations of high vitamin D and low retinol intake (RR = 0.55, 95% CI: 0.28, 1.10) further decreased risk of distal colorectal adenoma when compared with the opposite extreme. Higher total calcium and vitamin D intakes were associated with reduced risk, and the actions of vitamin D may be attenuated by high retinol intake.

Hypergastrinemia Is Associated with Increased Risk of Distal Colon Adenomas

Background/Aims:Helicobacter pylori infection is a recognized cause of hypergastrinemia, but the association of blood gastrin levels with colonic adenomas (CAs) is controversial. The aim of this study is to investigate if hypergastrinemia, H. pylori infection and/or cagA protein are risk factors for CAs. Methods: In this prospective case-control study, fasting serum samples from 78 consecutive patients with CAs and 78 demographically matched colonoscopy-negative controls were assayed for anti-H. pylori immunoglobulin G, cagA protein and serum gastrin levels. Multivariate analysis was performed to identify risk factors for colon adenomas. Results: Though prevalence of H. pylori antibodies was not significantly different, the prevalence of cagA protein was significantly higher in patients with adenomas (42.3%) as compared with controls (25.6%, p < 0.03). Mediangastrin levels were significantly higher in patients with CAs (55, 20–975 pg/ml) than in controls (45.2, 23–529 pg/ml) (p < 0.001). Hypergastrinemia (>110 pg/ml) was commoner in patients with CAs than in controls (29.5 vs. 11.5%, p = 0.006) and was the only independent risk factor for adenomas (odds ratio 3.2, 95% CI 1.4–7.5) by multivariate analysis, but not H. pylori infection or cagA positivity. There was a significant association of hypergastrinemia and distal distribution of adenomas (p < 0.002). Conclusions: Our study shows that hypergastrinemia is a risk factor for CAs, especially of the distal colon.

Meat Mutagens and Risk of Distal Colon Adenoma in a Cohort of U.S. Men

Cooking meats at high temperatures and for long duration produces heterocyclic amines and other mutagens. These meat-derived mutagenic compounds have been hypothesized to increase risk of colorectal neoplasia, but prospective data are unavailable. We examined the association between intakes of the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5,-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,4,8-trimethylimidazo[4,5,-f]quinoxaline (DiMeIQx), and meat-derived mutagenicity (MDM) and risk of distal colon adenoma using a cooking method questionnaire administered in 1996 in the Health Professionals Follow-up Study cohort. Between 1996 and 2002, 581 distal colon adenoma cases were identified. Higher intake of MDM was marginally associated with increased risk of distal adenoma [fourth versus lowest quintile: odds ratio (OR), 1.39; 95% confidence interval (95% CI), 1.05-1.84; highest versus lowest quintile: OR, 1.29; 95% CI, 0.97-1.72; P(trend) = 0.08]. Adjusting for total red meat or processed meat intake did not explain those associations. Our data also suggested a positive association between higher MeIQx (highest versus lowest quintile: OR, 1.28; 95% CI, 0.95-1.71; P(trend) = 0.22) and risk of adenoma, but this association was attenuated after adjusting for processed meat intake. DiMeIQx and PhIP did not seem to be associated with risk of adenoma. In conclusion, higher consumption of mutagens from meats cooked at higher temperature and longer duration may be associated with higher risk of distal colon adenoma independent of overall meat intake. Because mutagens other than heterocyclic amines also contribute to MDM, our results suggest that mutagens other than heterocyclic amines in cooked meats may also play a role in increasing the risk of distal adenoma.