Reduced Risk Of Colon Cancer Research Articles

Chemopreventive potential of in vitro fermented nuts in LT97 colon adenoma and primary epithelial colon cells.

Due to their beneficial nutritional profile the consumption of nuts contributes to a healthy diet and might reduce colon cancer risk. To get closer insights into potential mechanisms, the chemopreventive potential of different in vitro fermented nut varieties regarding the modulation of genes involved in detoxification (CAT, SOD2, GSTP1, GPx1) and cell cycle (p21, cyclin D2) as well as proliferation and apoptosis was examined in LT97 colon adenoma and primary epithelial colon cells. Fermentation supernatants (FS) of nuts significantly induced mRNA expression of CAT (up to 4.0-fold), SOD2 (up to 2.5-fold), and GSTP1 (up to 2.3-fold), while GPx1 expression was significantly reduced by all nut FS (0.8 fold on average). Levels of p21 mRNA were significantly enhanced (up to 2.6-fold), whereas all nut FS significantly decreased cyclin D2 expression (0.4-fold on average). In primary epithelial cells, expression of CAT (up to 3.5-fold), GSTP1 (up to 3.0-fold), and GPx1 (up to 3.9-fold) was increased, whereas p21 and cyclin D2 levels were not influenced. Nut FS significantly inhibited growth of LT97 cells and increased levels of early apoptotic cells (8.4% on average) and caspase 3 activity (4.6-fold on average), whereas caspase 3 activity was not modulated in primary colon cells. The differential modulation of genes involved in detoxification and cell cycle together with an inhibition of proliferation and induction of apoptosis in adenoma cells might contribute to chemopreventive effects of nuts regarding colon cancer.

Reduction in promotor methylation utilizing EGCG (epigallocatechin-3-gallate) restores RXRα expression in human colon cancer cells

Silencing of regulatory genes through hypermethylation of CpG islands is an important mechanism in tumorigenesis. In colon cancer, RXRα, an important dimerization partner with other nuclear transcription factors, is silenced through this mechanism. We previously found that colon tumors in ApcMin/+ mice had diminished levels of RXRα protein and expression levels of this gene were restored by treatment with a green tea intervention, due to reduced promoter methylation of RXRα. We hypothesized that CIMP+ cell lines, which epigenetically silence key regulatory genes would also evidence silencing of RXRα and EGCG treatment would restore its expression. We indeed found EGCG to restore RXRα activity levels in the human cell lines, in a dose dependent manner and reduced RXRα promoter methylation. EGCG induced methylation changes in several other colon cancer related genes but did not cause a decrease in global methylation. Numerous epidemiological reports have shown the benefits of green tea consumption in reducing colon cancer risk but to date no studies have shown that the risk reduction may be related to the epigenetic restoration by tea polyphenols. Our results show that EGCG modulates the reversal of gene silencing involved in colon carcinogenesis providing a possible avenue for colon cancer prevention and treatment.

High‐Calorie Diet Induced Chronic Colonic inflammation: A Human‐Relevant Porcine Model to Assess Whole Food Approach to Reduce Colon Cancer Risk

Recent studies have shown a critical link between high‐calorie diet (HCD)‐induced chronic inflammation and colon cancer. A recent prospective study revealed a positive association between interleukin‐6 (IL‐6), a pro‐inflammatory cytokine, and colon cancer risk. Recently, we developed a human‐relevant pig model for diet‐induced chronic inflammation where clinical markers of inflammation, calprotectin and LCN‐2, were elevated in colonic digesta and mucosa. In the current study, we hypothesized that HCD will elevate the IL‐6 signaling pathway proteins and these proteins levels will correlate with colon cancer risk (Ki‐67 proliferative index and zone) markers. We further hypothesized that anthocyanin rich purple‐fleshed potatoes suppress IL‐6 pathway proteins and colon cancer risk factors. We observed elevated colonic mucosal IL‐6 expression in HCD‐consuming pigs (3 weeks post‐weaning consumed diets for 13 weeks, n = 8 / group) compared to standard diet (SD, qPCR, P = 0.04) and IL‐6 expression levels strongly correlated with Ki‐67 proliferative index and zone (r = 0.604, 0.743; P = 0.017, 0.002; respectively). LC/MS‐MS‐based proteomic analysis and Ingenuity Pathway Analysis showed that HCD consumption alters IL‐6 signaling pathway proteins (PI3KR4, IL‐1α, Mapk10, Akt3, PIK3CG, PIK3R5, Map2k2). Furthermore, these proteins strongly correlated (r = 0.811, P = 0.001) with Ki‐67 proliferative index/zone. We observed that supplementation of HCD with anthocyanin containing purple‐fleshed potatoes (10% w/w), even after baking, tended to suppress HCD‐elevated IL‐6 expression (P ≤ 0.1) and IL‐6 linked proteins, IL‐1α and Map2k1 (P ≤ 0.1). Our results highlight the importance of IL‐6 signaling in diet‐linked induction/prevention of chronic colonic inflammation/cancer and demonstrate the potential of whole foods as a dietary intervention to counteract chronic inflammation and carcinogenesis using a human‐relevant pig model.Support or Funding InformationNational Research Initiative Grant 2009‐55200‐05197 from the USDA National Institute for Food and Agriculture (2009–2012)

Wheat Type (Class) Influences Development and Regression of Colon Cancer Risk Markers in Rats

We previously found red wheat more effective than white wheat in reducing colon cancer risk in rats when fed during initiation and postinitiation stages. Here we examine the effect of wheat on colon cancer risk in early and late postinitiation stages in carcinogen-treated rats. Four groups were fed a basal diet, 1 group a red wheat diet, and 1 group a white wheat diet. After 6 wk, 1 basal, the red and white groups were killed (early postinitiation stage). Of the remaining basal groups, 1 continued on the basal diet, 1 was switched to red and another to white wheat for 8 more wk (late postinitiation stage). Red and white wheat significantly reduced morphological [aberrant crypt foci (ACF)] and biochemical (β-catenin accumulated crypts) markers in both early and late postinitiation stages. Both wheat diets reduced dysplasia markers (sialomucin-expressing ACF and mucin depleted foci), compared to the basal diet, during the late postinitiation stage, but red wheat more so. Only red wheat significantly reduced the number of metallothionein-positive crypts, a stem cell mutation marker, in both stages. Overall, red wheat flour reduced risk markers more than white wheat flour, and this was more pronounced in the late post-initiation stage.

Impact of palm date consumption on microbiota growth and large intestinal health: a randomised, controlled, cross-over, human intervention study.

The reported inverse association between the intake of plant-based foods and a reduction in the prevalence of colorectal cancer may be partly mediated by interactions between insoluble fibre and (poly)phenols and the intestinal microbiota. In the present study, we assessed the impact of palm date consumption, rich in both polyphenols and fibre, on the growth of colonic microbiota and markers of colon cancer risk in a randomised, controlled, cross-over human intervention study. A total of twenty-two healthy human volunteers were randomly assigned to either a control group (maltodextrin-dextrose, 37·1 g) or an intervention group (seven dates, approximately 50 g). Each arm was of 21 d duration and was separated by a 14-d washout period in a cross-over manner. Changes in the growth of microbiota were assessed by fluorescence in situ hybridisation analysis, whereas SCFA levels were assessed using HPLC. Further, ammonia concentrations, faecal water genotoxicity and anti-proliferation ability were also assessed using different assays, which included cell work and the Comet assay. Accordingly, dietary intakes, anthropometric measurements and bowel movement assessment were also carried out. Although the consumption of dates did not induce significant changes in the growth of select bacterial groups or SCFA, there were significant increases in bowel movements and stool frequency (P<0·01; n 21) and significant reductions in stool ammonia concentration (P<0·05; n 21) after consumption of dates, relative to baseline. Furthermore, date fruit intake significantly reduced genotoxicity in human faecal water relative to control (P<0·01; n 21). Our data indicate that consumption of date fruit may reduce colon cancer risk without inducing changes in the microbiota.

PWE-019 Polyp detection rate. does length matter?

<h3>Introduction</h3> Polyp detection is a vital for any colonoscopist to reduce colon cancer risk. The USA National Polyp Study reported that endoscopic removal of all adenomas was associated with a 76–90% decrease in cancer incidence compared to 3 separate historic reference groups. Polyp detection rate (PDR) depends on factors such as withdrawal time and quality of bowel prep. Our study assessed whether the physical distance of the endoscopist to the live screen had a significant relationship to the PDR, the latter being a surrogate marker for adenoma detection rate. <h3>Method</h3> Using endoscopy reports we retrospectively compared the PDR at colonoscopy and flexible sigmoidoscopy in 2 separate hospitals each with 2 endoscopy rooms over a 12 month period. Endoscopists work cross site and across all rooms. The distances between the endoscopist and the screen were measured. In hospital A there is a marked difference in distance between the endoscopist to screen when comparing the two endoscopy rooms. In hospital B the endoscopist to screen distances are identical in the 2 rooms and we used this as a control group. A paired t test was used for statistical analysis Significance was set at p &lt; 0.01 <h3>Results</h3> In hospital A, 1,086 lower GI examinations were done in room 1 with a PDR of 35.3% with endoscopist to screen measurement at 219 cm. In room 2, 1,040 lower GI exams were done with a PDR of 45.4% and an endoscopist to screen measurement of 147 cm. The PDR was significantly higher in the room where the monitor was 72 cm closer to the endoscopist (p &lt; 0.00001). In hospital B, there were no significant differences in PDR detected at colonoscopy between the two endoscopy rooms (40% v 34.2%, monitor distance 190 cm). <h3>Conclusion</h3> Both JAG and the World Endoscopy Organisation have issued guidelines on the construction of an endoscopy unit. There is limited information on the significances of distances between an endoscopist and the screen. Our study highlights that this may be a factor to consider when designing an endoscopy room. The room with the closest screen had the highest PDR at colonoscopy. Our work suggests that the closer the endoscopist is to the screen the higher the polyp detection rate. More work may determine the optimum endoscopist to screen distance for PDR. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Winawer SJ, Zauber AG, Ho MN, <i>et al</i><i>. Prevention of colorectal cancer by colonoscopic polypectomy</i>. The National Polyp Study Workgroup. N Engl J Med 1993;329:1977 Mulder CJ, Jacobs, MAJM, <i>et al</i>. Guidelines for designing a digestive disease endoscopy.unit: report of the world endoscopy organization. Dig Endosc.2013;25:365–375 http://www.thejag.org.uk/downloads%5CUnit%20Resources%5CUsers%20guide%20to%20achieving%20a%20JAG%20compliant%20endoscopy%20environment.pdf

Regulation of VDR Expression in Apc-Mutant Mice, Human Colon Cancers and Adenomas.

One variable that may affect the ability of vitamin D to reduce colon cancer risk is the expression of its high-affinity receptor, VDR. Here, we show that vitamin D does not reduce tumor formation in Apc(Δ14/+) mice and that VDR expression is lost in the majority of the colon tumor cells. The extent of VDR loss corresponded inversely to the level of β-catenin nuclear localization and could be observed in early lesions composed of just a few crypts. Analysis of reported VDR regulators showed that the repressing class I histone deacetylases (HDAC) were significantly elevated in the tumors (up to 4-fold), whereas the VDR-activating retinoid X receptors (RXR) were downregulated (∼50%). Expression of the Slug repressor was also increased, but was found primarily in stromal cells. Analysis of epigenetically active compounds on colon cell lines and intestinal organoids showed that HDAC inhibitors were particularly adept at stimulating VDR expression. Treatment of tumor-bearing Apc(Δ14/+) mice with the HDAC inhibitor panobinostat increased VDR expression in the tumors and normal mucosa. The RXR agonist bexarotene failed to activate VDR expression, indicating that RXR ligands were not limiting. Analysis of human microarray data indicated that VDR mRNA is frequently downregulated in colon adenomas, which correlated positively with RXRA expression and inversely with HDAC 2 and 8 expression. Human adenomas showed variable VDR protein expression levels, both between and within individual lesions. Determining the mechanisms of VDR regulation in colon neoplasms may significantly enhance our ability to use vitamin D as a cancer prevention agent.

Chemoprotective natural compounds targeting DNA damaged stem cells‐ the cells of origin of colon cancer

The majority of colon tumors are triggered by aberrant Wnt signaling in intestinal stem cells, which is an extremely efficient route towards initiating intestinal cancer. Curcumin, a component of turmeric, and n‐3 polyunsaturated fatty acids (PUFAs), mainly found in fish oil, exert chemoprotective and anti‐inflammatory properties in part by modulating apoptotic, Wnt, and/or NFkappaB related pathways. However, the chemoprotective effects of diet on colonic adult stem cells‐the cells of origin of colon cancer are unknown. Therefore, we determined whether the combination of fish oil (FO) and curcumin (C) reduce colon cancer risk by modulating targeted apoptosis, DNA damage repair and proliferation in colonic Lgr5+ stem cells at the initiation stage of cancer compared to corn oil (CO, control) by utilizing Lgr5‐EGFP‐IRES‐creERT2 knock‐in mice fed diets containing CO±C or FO±C for 3 weeks followed by carcinogen (azoxymethane) injection. Interestingly, FO+C combination synergistically increased apoptosis (TUNEL) by 5‐fold, and promoted targeted DNA repair (MGMT+) by 9‐fold in DNA damaged (gamma H2AX+) stem cells compared to control. In general, stem cells were more responsive to environmental (carcinogen &amp; diet) cues compared to non‐stem cells. These novel results demonstrate the unique ability of colonic stem cells to respond to external cues.

Cholecalciferol or 25-Hydroxycholecalciferol Neither Prevents Nor Treats Adenomas in a Rat Model of Familial Colon Cancer ,

Epidemiologic studies in humans have shown associations between greater sunlight exposure, higher serum 25-hydroxycholecalciferol [25(OH)D3] concentrations, and reduced colon cancer risk. However, results from a limited number of vitamin D supplementation trials in humans have not shown a protective effect. We sought to determine whether adding to the diet increasing amounts of either 25(OH)D3, the stable metabolite measured in serum and associated with cancer risk, or cholecalciferol (vitamin D3), the compound commonly used for supplementation in humans, could reduce emergent adenomas (chemoprevention) or decrease the growth of existing adenomas (treatment) in the colons of vitamin D-sufficient rats carrying a truncation mutation of adenomatous polyposis coli (Apc), a model of early intestinal cancer. Apc(Pirc/+) rats were supplemented with either vitamin D3 over a range of 4 doses [6-1500 μg/(kg body weight · d)] or with 25(OH)D3 over a range of 6 doses [60-4500 μg/(kg body weight · d)] beginning after weaning. Rats underwent colonoscopy every other week to assess effects on adenoma number and size. At termination (140 d of age), the number of tumors in the small intestine and colon and the size of tumors in the colon were determined, and serum calcium and 25(OH)D3 measurements were obtained. At lower doses (those that did not affect body weight), neither of the vitamin D compounds reduced the number of existing or emergent colonic tumors (P-trend > 0.24). By contrast, supplementation at higher doses (those that caused a suppression in body weight gain) with either 25(OH)D3 or vitamin D3 caused a dose-dependent increase in colonic tumor number in both males and females (P-trend < 0.003). No evidence for protection against colon tumor development was seen with lower dose supplementation with either cholecalciferol or 25-hydroxycholecalciferol. Thus, the association between sunlight exposure and the incidence of colon cancer may involve factors other than vitamin D concentrations. Alternative hypotheses warrant investigation. Furthermore, this study provides preliminary evidence for the need for caution regarding vitamin D supplementation of humans at higher doses, especially in individuals with sufficient serum 25(OH)D3 concentrations.

5,10-Methylenetetrahydrofolate reductase polymorphisms and colon cancer risk: a meta-analysis.

Previous studies investigating the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and colon cancer risk have generated conflicting results. The aim of our meta-analysis was to clarify the precise association. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CI) were used to estimate the strength of the association. In this meta-analysis, a total of 13 articles, involving 5,386 cases and 8,017 controls met the inclusion criteria. Overall, a significant association was found between colon cancer risk and the MTHFR C667 polymorphism (TT vs CC+CT: OR=0.79; 95%CI=0.65-0.96; p=0.017). Stratification by ethnicity revealed that MTHFRC667 was associated with colon cancer risk in the non-Asian group (TT vs CC+CT:OR=0.77, 95%CI=0.68-0.89, p=0.000; TT vs CC: OR=0.84, 95%CI=0.73-0.97, p=0.016). Stratification by source of control indicated that MTHFR C667 also correlated with colon cancer risk in the population-based subgroup (TT vs CC: OR=0.85, 95%CI=0.74-0.97, p=0.017; TT vs CC+CT: OR=0.78, 95%CI=0.68-0.89, p=0.000) and hospital-based subgroup (TT vs CC+CT: OR=0.65, 95%CI=0.49-0.86, p=0.003). However, risk was significantly increased for MTHFR A1298C polymorphisms and colon cancer risk in hospital-based studies (C vs A: OR=1.52, 95%CI=1.26-1.83, p=0.000; CC+AC vs AA: OR=1.93, 95%CI=1.47-2.49, p=0.000) but reduced in population-based studies (CC vs AA: OR=0.83, 95%CI=0.70-0.99, p=0.042). In conclusion, the results of our meta-analysis suggest that the MTHFR C667 polymorphism is associated with reduced colon cancer risk, especially for non-Asian populations.

Resistant starch may reduce colon cancer risk from red meat.

Resistant starch may reduce colon cancer risk from red meat.

Mechanisms by Which Pleiotropic Amphiphilic n-3 PUFA Reduce Colon Cancer Risk.

Colorectal cancer is one of the major causes of cancer-related mortality in both men and women worldwide. Genetic susceptibility and diet are primary determinants of cancer risk and tumor behavior. Experimental, epidemiological, and clinical data substantiate the beneficial role of n-3 polyunsaturated fatty acids (PUFA) in preventing chronic inflammation and colon cancer. From a mechanistic perspective, n-3 PUFA are pleiotropic and multifaceted with respect to their molecular mechanisms of action. For example, this class of dietary lipid uniquely alters membrane structure/ cytoskeletal function, impacting membrane receptor function and downstream signaling cascades, including gene expression profiles and cell phenotype. In addition, n-3 PUFA can synergize with other potential anti-tumor agents, such as fermentable fiber and curcumin. With the rising prevalence of diet-induced obesity, there is also an urgent need to elucidate the link between chronic inflammation in adipose tissue and colon cancer risk in obesity. In this review, we will summarize recent developments linking n-3 PUFA intake, membrane alterations, epigenetic modulation, and effects on obesity-associated colon cancer risk.

S1pping fire: Sphingosine-1-phosphate signaling as an emerging target in inflammatory bowel disease and colitis-associated cancer

Inflammatory bowel disease (IBD) is a complex disease that involves unpredictable and destructive inflammation in the gastrointestinal tract resulting in gastrointestinal symptoms, infection, and tissue destruction, and which can be associated with an increased risk of colon cancer. The underlying cause of IBD involves disruption of the innate and adaptive immune mechanisms that maintain homeostasis between the gut mucosa and its environment. Elucidating how the homeostatic mechanisms controlling gut mucosal immunity and inflammation are disrupted in IBD represents the first steps to identifying novel therapeutic targets. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that is enriched in the blood and lymph, and functions in innate and adaptive immunity. S1P signaling regulates inflammation via its impact on the trafficking, differentiation, and effector functions of bone marrow-derived immune cells. S1P also activates nuclear factor kappa B and signal transducer and activator of transcription 3 inflammatory pathways. S1P is generated by the ubiquitously expressed lipid kinase, sphingosine kinase (SphK)1 and its tissue-restricted homolog, SphK2. S1P is irreversibly degraded by S1P lyase, which is highly expressed in enterocytes. Recent studies targeting S1P metabolism and signaling have shown promise in preclinical models of IBD and have shed light on the mechanisms by which S1P signaling impacts IBD. The evidence suggests that targeting S1P signaling and metabolism may represent a novel strategy in treating IBD and it may reduce colon cancer risk by interrupting the progression from inflammation to carcinogenesis.

Wheat Color (Class), Not Refining, Influences Colon Cancer Risk in Rats

Epidemiological studies suggest whole grain consumption is associated with decreased colon cancer risk. However, wheat classes differ in their usage, making the influence of wheat class (red vs. white) and state of refinement (whole vs. refined) difficult to separate, leading to potential confounding. Consequently, we examined the effect of wheat class and refining on colonic precancerous lesions (aberrant crypt foci; ACF) in carcinogen-treated rats. Diets contained wheat flour as whole soft white, refined soft white, whole hard red, or refined hard red. Feeding was begun 10 days prior to carcinogen treatment and continued for 9 wk. Hard red-fed groups had significantly fewer ACF than soft white-fed groups (25–32% reduction, P = 0.013). However, state of refinement had no significant effect on ACF number. Cecal contents supernatant oxygen radical absorbance capacity and fecal bile acid concentration were significantly greater in whole wheat-fed groups than refined wheat-fed groups and did not correlate with ACF number (increase of 21–22%, P < 0.001 and 55–56%, P < 0.001, respectively). Consequently, wheat class, not state of refinement, appears to influence colon cancer risk, with hard red wheat protective relative to soft white wheat. Thus, epidemiological associations of reduced colon cancer risk with whole grain consumption may actually reflect different wheat classes.

Sa1958 Serrated Polyposis Syndrome: Pushing Through Prevalence and Clinicopathological Features

G A A b st ra ct s diet alone group (p<0.05). INCB3619 significantly inhibited pEGFR and pErbB2 signals in intestinal adenomas. Colon tumor incidence was 0.33 in the INCB3619-treated group, compared to 0.83 in Western diet alone group (p=0.10). Summary INCB3619 significantly reduced intestinal tumor multiplicity and tumor size in Apc Min mice. INCB3619 also concomitantly suppressed intestinal mucosal ADAM17 enzyme activity as well as EGFR signals in intestinal adenomas. Conclusions Our results show that targeting ADAM17 inhibits intestinal tumor promotion byWestern diet.We postulate thatWestern diet promotes tumorigenesis by activating ADAM17 and up-regulating EGFR signals. Our studies suggest that ADAM17 inhibitors might provide a novel strategy to reduce colon cancer risk in individuals consuming Western diets.

Effects of chemoprotective diets on crypt adult stem cells û the cells of origin of colon cancer (819.1)

The majority of colon tumors are triggered by aberrant Wnt signaling in intestinal stem cells, which is an extremely efficient route towards initiating intestinal cancer. Curcumin, a component of turmeric, and n‐3 polyunsaturated fatty acids (PUFAs), mainly found in fish oil, exert chemoprotective and anti‐inflammatory properties in part by modulating apoptotic, Wnt, and/or NFκB related pathways. However, the effects of diet on colonic stem cells are unknown. Therefore, we determined whether the combination of fish oil and curcumin reduced colon cancer risk by promoting targeted apoptosis of damaged colonic stem cells at the initiation stage of cancer. Lgr5‐EGFP‐IRES‐creERT2 knock in mice (n=10 per treatment) were fed diets containing corn oil ± curcumin (CO±C) or fish oil ± curcumin (FO±C) for 3 weeks. Apoptosis, cell proliferation and DNA damage in Lgr5+ stem cells were quantified 12 h post carcinogen (azoxymethane) injection. Interestingly, mice fed FO diets exhibited 15% fewer stem cells per crypt and an enhanced resistance to DNA damage, with 52% fewer damaged stem cells. For those stem cells exhibiting DNA damage, FO feeding enhanced targeted apoptosis by 24% compared to CO diets. In contrast, curcumin had no significant effects on stem cell responses. These novel results demonstrate the chemoprotective ability of external dietary cues to impact intestinal stem cell responses following carcinogen exposure.

Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study

Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; ptrend = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; ptrend = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.

Relationships between Serum and Colon Concentrations of Carotenoids and Fatty Acids in Randomized Dietary Intervention Trial

Little is known about the effect of preventive diets on colonic nutrient concentrations. This study randomized 120 persons at increased risk of colon cancer to a Mediterranean versus a Healthy Eating diet for six months. The former targeted increases in whole grains, fruits, vegetables, monounsaturated, and n3 fats. The Healthy Eating diet was based on Healthy People 2010 recommendations. At baseline, dietary fat and carotenoid intakes were poorly associated (Spearman ρ < 0.4) with serum and colon concentrations. Strong associations were observed between serum and colon measurements of β-cryptoxanthin (ρ = 0.58; P < 0.001), α-carotene (ρ = 0.48; P < 0.001), and β-carotene (ρ = 0.45; P < 0.001). After six months, the Healthy Eating intervention increased serum lutein, β-, and α-carotene significantly (P < 0.05). In the Mediterranean arm, the significant increases were in serum lutein, β-cryptoxanthin, β-carotene, monounsaturated, and n3 fats. A significant group-by-time interaction (P = 0.03) was obtained for monounsaturated fats. Colonic increases in carotenoids and n3 fats were significant only in Healthy Eating arm, whereas the group-by-time interaction was significant for β-carotene (P = 0.02) and α-carotene (P = 0.03). Changes in colon concentrations were not significantly associated with reported dietary changes. Changes in colon and serum concentrations were strongly associated for β-cryptoxanthin (ρ = 0.56; P < 0.001) and α-carotene (ρ = 0.40; P < 0.001). The associations between colonic and serum concentrations suggest the potential use of using serum concentration as a target in dietary interventions aimed at reducing colon cancer risk.

Diabetes, metformin use, and colon cancer: a population-based cohort study in Taiwan

A retrospective cohort study, using a population-based reimbursement database, was conducted for investigating the relationship between diabetes and colon cancer and assessing whether metformin had a protective effect. Overall, 493,704 men and 502,139 women, covered by the National Health Insurance, without colon cancer were followed from 2003 to 2005. Cox regression evaluated the adjusted relative risk (RR), considering confounders and detection examinations. Even though diabetes patients had a significantly higher probability of receiving examinations that could lead to the detection of colon cancer, they had a significantly higher risk (24%) of this cancer after adjustment. Metformin users had a significantly lower risk (27%) of colon cancer. While comparing patients with diabetes for <1, 1-3, and ≥ 3 years to nondiabetes individuals, the adjusted RR (95% confidence interval) was 1.308 (1.020-1.679), 1.087 (0.900-1.313), and 1.185 (1.055-1.330) respectively. The higher risk among those with diabetes for <1 year suggested a possible reverse causality or a link with prediabetes. However, diabetes still might play some role in the development of colon cancer in those with diabetes for ≥ 3 years. The duration of metformin use showed an inverse trend, with a significant RR of 0.643 (0.490-0.845) in users for ≥ 3 years, when compared with nonusers. In addition, metformin may reduce colon cancer risk associated with chronic obstructive pulmonary disease (a surrogate for smoking). Following adjustment for potential detection bias and other covariates, diabetes remains a significant risk factor for colon cancer. Metformin may protect against colon cancer.

Reduction in Colon Cancer Risk by Consumption of Kava or Kava Fractions in Carcinogen-Treated Rats

Epidemiological studies suggest that kava reduces colon cancer risk. However, no experimental studies of the chemopreventive properties of kava toward colon cancer have been reported. Further, there are concerns regarding hepatotoxicity of kava. The goal of this study was to determine whether kava consumption reduces markers of colon cancer in an animal model and to study the safety of kava. An ethanolic extract and polar and nonpolar fractions of the kava extract were fed to rats for 12 days prior to, during, and after administration of dimethylhydrazine, a colon-specific carcinogen. After 14 wk, rats fed the nonpolar extract had a significant reduction in precancerous lesions [aberrant crypt (AC) foci (ACF)] as well as large (≥4 AC/ACF) sialomucin-only expressing foci, an indicator of greater tumorigenic potential, compared to the control group. Groups fed the ethanolic extract and polar kava fraction trended toward reductions in ACF and large sialomucin-only expressing foci. The combined kava groups had significantly fewer total AC, ACF, large ACF, and large sialomucin-only expressing foci compared to the control group. Histological examination found no hepatic lesions in animals consuming the kava diets, suggesting that kava is safe to consume. Our results support that kava may reduce colon cancer risk.