Development Of Colonic Polyps Research Articles

Causal Relationships between Polyunsaturated Fatty Acids and Colon Polyps: A Two-Sample Mendelian Randomization Study.

Epidemiological studies have shown that fatty acids, especially polyunsaturated fatty acids (PUFAs), influence colorectal carcinogenesis. Colon polyps, particularly those identified as precancerous, are a frequently encountered phenomenon associated with PUFAs. However, the results are inconsistent. Therefore, we investigated the effect of PUFAs on colon polyps in individuals of European ancestry. Single nucleotide polymorphisms correlating with PUFAs and colon polyps were derived from extensive genome-wide association studies, encompassing a discovery cohort of 135,006 samples and a corresponding validation set with 114,999 samples. Causality was assessed by employing a range of techniques, such as inverse variance weighted (IVW), weighted median, MR-Egger, and simple and weighted modes. The analysis was complemented with sensitivity checks using leave-one-out and heterogeneity evaluation through MR-IVW and Cochran's Q. A thorough analysis was performed to examine the causal effects of PUFAs on the development of colon polyps. The findings indicated that levels of Omega-3 fatty acids (OR = 1.0014, 95% CI 1.0004-1.0024, p = 0.004), the ratio of Docosahexaenoic acid (DHA)/total fatty acids (FAs) (DHA/totalFA; OR = 1.0015, 95% CI 1.0002-1.0028, p = 0.023), and the ratio of Omega-3/totalFA (Omega-3/totalFA; OR = 1.0013, 95% CI 1.0003-1.0022, p = 0.010) were identified as biomarkers associated with an increased risk of colon polyps. Conversely, the ratio of Omega-6/Omega-3 (OR = 0.9986, 95% CI 0.9976-0.9995, p = 0.003) and the ratio of Linoleic acid (LA)/totalFA (LA/totalFA; OR = 0.9981, 95% CI 0.9962-0.9999, p = 0.044) were negatively associated with susceptibility to colon polyps. The MR-Egger and MR-IVW analysis revealed that pleiotropy and heterogeneity did not significantly impact the outcomes. This study has uncovered a possible adverse effect of PUFAs, notably Omega-3, on the formation of colon polyps. Elevated Omega-3 levels were correlated with a heightened risk of colon polyps.

Oxidative imbalance increases the risk for colonic polyp and colorectal cancer development.

The role of oxidative stress in the pathogenesis of colorectal carcinoma (CRC) has garnered considerable interest recently. Specific oxidative factors have been implicated in the pathogenesis of adenomatous polyps and ultimately adenocarcinoma. To evaluate the effect of oxidative imbalance as quantified by specific serological markers in the development of sporadic colon adenocarcinoma. A total of 170 patients that underwent endoscopy of the lower gastrointestinal tract in a tertiary center within 3 years were included in the study. They were allocated in three groups; those with sporadic colon adenocarcinoma (n = 56, 32.9%), those with colonic polyps (n = 33, 19.4%) and healthy controls (n = 81, 47.7%). All patients were evaluated for oxidant activity and antioxidant capacity with serum measurements of specific markers such as vitamins A, 25(OH) D3, E, C, B12, folic acid, glutathione, selenium (Se), zinc (Zn), free iron (Fe2+), and malondialdehyde and results were compared between groups. Serum levels of vitamins C, E, D, Se, Zn, vitamin B12 and total antioxidant capacity were significantly lower in the combined neoplasia/polyp group than in the control group (P = 0.002, P = 0.009, P < 0.001, P < 0.001, P < 0.001, P = 0.020 and P < 0.001, correspondingly). Increased levels of vitamin E (P = 0.004), vitamin D (P < 0.001), Se (P < 0.001) and Zn (P < 0.001) seem to bestow a protective effect on the development of CRC. For vitamin D (P < 0.001) and Zn (P = 0.036), this effect seems to extend to the development of colon polyps as well. On the other hand, elevated serum levels of malondialdehyde are associated with a higher risk of CRC (OR = 2.09 compared to controls, P = 0.004). Regarding colonic polyp development, increased concentrations of vitamin Α and Fe2+ are associated with a higher risk, whereas lower levels of malondialdehyde with a lower risk. Increased oxidative stress may play an important role in the pathogenesis and progression of CRC. Antioxidants' presence may exert a protective effect in the very early stages of colon carcinogenesis.

GH Is a Component of SASP in Aging Tissue

Deficient GH signaling results in lifespan extension in murine and human models, while patients with uncontrolled acromegaly and transgenic mice overexpressing GH have a shorter lifespan. Colon polyp development increases with age, and also with GH excess in acromegaly. Aging is characterized by senescent cell accumulation with p53/p21 or p16 upregulation as well as cell cycle arrest and expression of a senescence-associated secretory phenotype (SASP). Senescence is reinforced by the SASP, which comprises pro-inflammatory cytokines, chemokines, growth modulators, angiogenic factors, and matrix metalloproteinases. SASP contributes to pro-aging phenotypes, and depletion or removal of senescent cells increases lifespan by partially protecting from age-related pathologies. Senescence, triggered by genotoxic insult with DNA damage, can be reversed by p53 inactivation; senescent cells with low p53 and unrepaired DNA damage can then re-enter the cell cycle (Beausejour et al, EMBO 2003), potentially resulting in chromosomal instability. We showed GH induction in non-pituitary senescent cells leading to suppressed p53/p21 (Chesnokova PNAS 2013). We now show that, in senescent human colon cells (hNCC) and in 3-dimensional human intestinal organoids, non-pituitary GH (npGH) is a component of SASP. In response to DNA damage, npGH is expressed and secreted locally as measured by RT-PCR, WB, and ELISA. High autocrine/paracrine GH further exacerbate DNA damage and reverses senescent in colon cells, enabling them to re-enter the cell cycle, as evidenced by p53 downregulation and increased Ki67 expression. Senescent colon cells expressing high intracellular GH form colonies in soft agar, indicative of cell transformation and proliferation, while GH deletion by shRNA results in Ki67 downregulation and decreased colony formation and size. The SASP protein CXCL1, a chemo-attractant that also functions to eliminate senescent cells, dose-dependently activates GH in hNCC and in intestinal organoids. GH, in turn, suppresses CXCL1 expression. Consistent with these findings, colon CXCL1 was induced in GHRKO mice, and also in hNCC with abrogated GH signaling by shRNA. Taken together with our finding that GH accumulates in aging normal human colon tissue and co-localizes in cells expressing senescence-associated β-galactosidase, these results suggest that GH, as a SASP component, initiates senescent cell proliferation and transformation. By inhibiting CXCL1, GH also functions to attenuate immune-mediated senescent cell elimination that protects aging tissue from deleterious effects of SASP. These mechanisms may underly an initial step in age-associated epithelial polyp development.

Possible protective role of metformin therapy on colonic polyps in acromegaly: an exploratory cross-sectional study.

Colonic polyps occur in 30-40% of acromegalic patients, increasing the risk of colon carcinoma. Although debated, there is emerging evidence that metformin may play a protective role in diabetic and non-diabetic patients with colonic polyps and its use in chemoprevention is currently explored. Evaluate the prevalence of colonic polyps in acromegalic patients treated or not with metformin and explore its possible protective role. Exploratory cross-sectional study in two tertiary Italian referral centres. hods: Out of 153 acromegalic patients, we selected 58 patients (36-82 years; f: 33) who had at least one colonoscopy performed within the first 2 years of diagnosis. Presence of colonic polyps/cancer and related risk factors, current metformin and acetylsalicylic acid intake, disease duration, therapies for acromegaly, hormonal and metabolic parameters were assessed. An overall prevalence of 36% polyps was found. Based on the presence of polyps, we identified two groups, comparable for age, BMI, disease duration, glucose, insulin, HOMA-IR, HbA1c, GH and IGF-I levels. Of the patients with polyps (including three adenocarcinomas) only 24% were treated with metformin vs 57% of patients without polyps. Multivariate analysis confirmed a significant negative association between colonic polyps and metformin intake (OR: 0.22, 95% CI: 0.06-0.77, P = 0.01), whereas no significant association was found between polyps and age (P = 0.10), overweight/obesity (P = 0.54), smoking (P = 0.15), acetylsalicylic acid intake (P = 0.99), disease duration (P = 0.96), somatostatin analogues treatment (P = 0.70). These findings, though deriving from an exploratory study, could suggest a protective role of metformin on the development of colonic polyps in acromegaly, and need to be confirmed in an extended study population.

716. A Case of Symptomatic Intestinal Spirochetosis

BackgroundIntestinal spirochetosis (IS) is a condition caused by Brachyspira aalborgi and Brachyspira Pilosicoli. Its clinical significance has long been a point of contention with some debating that these spirochetes are simply colonic commensals. It is a condition that is more prevalent in developing nations as well as patients with HIV and the homosexual population. The epidemiology and prevalence of IS has not been studied in the local context.MethodsWe reviewed a case of a 37-year-old man who presented with a two month history of persistent lower abdominal pain, hematochezia, and increase in mucous discharge per rectum. He is sexually active with multiple male partners, and was previously treated for gonorrhea, chlamydia, and syphilis. His basic laboratory investigations were unremarkable, Venereal Disease Research Laboratory (VDRL) antibody and human immunodeficiency virus (HIV) screen were both non-reactive. Computed tomography of the abdomen was unremarkable. Endoscopic evaluation revealed multiple discrete ulcers measuring 1-2mm seen only in the rectum. Random biopsies of the cecum, ascending colon, transverse colon and descending colon showed mild acute colitis with IS. There was also mild to moderate acute proctitis in the rectum with spirochetes seen. 16s RNA gene sequencing of the biopsy specimen were confirmatory for Brachyspira aalborgi.Investigation findings. A: Discrete Ulcers found in rectum, B: Hemotoxylin and Eosin stained specimen showing proctitis, C: False brush Border appearance D: Spirochetes on Warthin Starry stain ResultsThe patient received a 10 day course of metronidazole with complete resolution of his symptoms.ConclusionThis case demonstrates the existence of a treatable condition that can be diagnosed with current available investigations for patients with similar symptoms. Recognising at risk populations can also raise clinical suspicion for this condition. Some studies have found associations between IS with development of colonic polyps and also certain colorectal cancers. Further studies on this treatable condition and its disease burden in the local context should be further explored.Disclosures All Authors: No reported disclosures

Plasma adiponectin, visfatin, leptin, and resistin levels and the onset of colonic polyps in patients with prediabetes

BackgroundPrediabetes is associated with a high risk of colon cancer, and abdominal obesity, which can result in the secretion of several obesity-related adipocytokines, is an independent influencing factor for colonic polyps in prediabetes subjects. However, the correlation between adipocytokine levels and colonic polyps in prediabetes subjects is unclear. This research explores the relationship between plasma adiponectin, visfatin, leptin, and resistin levels and the development of colonic polyps in prediabetes subjects.MethodsA total of 468 prediabetes subjects who underwent electronic colonoscopy examinations were enrolled in this study; there were 248 cases of colonic polyps and 220 cases without colonic mucosal lesions. Then, colonic polyps patients with prediabetes were subdivided into a single-polyp group, multiple-polyps group, low-risk polyps group, or high-risk polyps group. In addition, 108 subjects with normal glucose tolerance who were frequency matched with prediabetes subjects by sex and age were selected as the control group; 46 control subjects had polyps, and 62 control subjects were polyp-free. Plasma adiponectin, visfatin, leptin, and resistin levels were measured in all the subjects, and the related risk factors of colonic polyps in prediabetes subjects were analysed.ResultsPlasma adiponectin levels were significantly lower in the polyps group than in the polyp-free group [normal glucose tolerance (9.8 ± 4.8 vs 13.3 ± 3.9) mg/L, P = 0.013; prediabetes (5.6 ± 3.7 vs 9.2 ± 4.4) mg/L, P = 0.007]. In prediabetes subjects, plasma adiponectin levels were decreased significantly in the multiple polyps group [(4.3 ± 2.6 vs 6.7 ± 3.9) mg/L, P = 0.031] and the high-risk polyps group [(3.7 ± 2.9 vs 7.4 ± 3.5) mg/L, P < 0.001] compared to their control groups. Plasma visfatin levels were higher in the polyps group and the multiple-polyps group than those in their control groups (P = 0.041 and 0.042, respectively), and no significant difference in plasma leptin and resistin levels was observed between these three pairs of groups (all P > 0.05). The multivariate logistic regression analysis showed that lower levels of plasma adiponectin was a risk factor for colonic polyps, multiple colonic polyps, and high-risk colonic polyps in prediabetes subjects.ConclusionsPlasma adiponectin levels are inversely associated with colonic polyps, multiple colonic polyps, and high-risk colonic polyps in prediabetes subjects. And adiponectin may be involved in the development of colon tumours in prediabetes subjects.

Experience of general surgical procedures in patients after heart transplantation

To study the frequency of general surgical diseases development snd their features in patients after heart transplantation (HTx). From January 2010 to December 2018 it was performed 112 HTx (mean age - 46.7±14.0 years old; 82 - male, 30 - female). During 30 days after HTx 9 patients died. After discharge all recipients (n=98) were included in dispensary observation list. We retrospectively analyzed patients (n=35) who underwent general surgery manipulations in more than 30 days after HTx. All surgical interventions have been done under the reduction of immunosuppression therapy. During 9 years of post-heart transplant follow-up 45 surgical interventions were performed, 7% (n=3) of them due to infectious complications, 31% (n=14) - oncology and others (62%, n=28). Most of manipulations were planned (39 from 45, 87%), the following general surgery interven- tions prevailed: laparoscopic cholecystectomy (n=13) and those to remove inguinal and umbilical hernia (n=12). During the 1st year the frequency of diseases required surgical treatment was 26% (n=11), infectious causes took place in 5 patients, non-infectious - in 6. Subsequently the incidence of infectious complications decreased that could be associated with the minimization of immunosuppressive therapy. Oncology was more frequent long-term after HTx - more than 3 years: among them the development of colon polyps prevailed and all recipients underwent polypectomy. There was no impact of age, gender, causes of chronic heart failure, obesity, immunosuppressive regimen (including the induction) on the frequency of general surgery diseases development (p&gt;0.05). Based on our experience, we proposed an algorithm of examination, the features of surgical tactics and preparation for it in heart transplanted recipients are described. The important role of post-heart transplant follow-up in the timely detection of diseases requiring general surgical care is given.

Cholera Vaccine Use Is Associated With a Reduced Risk of Death in Patients With Colorectal Cancer: A Population-Based Study

Cholera toxin can act as a modulator of the immune response with anti-inflammatory effects; it reduces development of colon polyps in mouse models of colorectal cancer (CRC). We performed a population-based study to determine whether, in patients with a diagnosis of CRC, subsequent administration of the cholera vaccine (killed Vibrio cholerae O1 whole cells and recombinant cholera toxin B subunit) affects mortality. We identified patients from the Swedish Cancer Register who were diagnosed with CRC from July 2005 through December 2012. These patients were linked to the Swedish Prescribed Drug Register toretrieve cholera vaccine use. We used Cox regression analysis to calculate the hazard ratio (HR) of death from CRC and overall mortality in patients with post-diagnostic use of cholera vaccine compared with matched controls. A total of 175 patients were diagnosed with CRC and given a prescription for the cholera vaccine after their cancer diagnosis. Compared with propensity score-matched controls and adjusted for confounding factors, patients with CRC whoreceived the cholera vaccine had a decreased risk of death from CRC (HR, 0.53; 95% CI, 0.29-0.99) and a decreased risk of death overall (HR, 0.59; 95% CI, 0.37-0.94). The decrease in mortality with cholera vaccination was largely observed, irrespective of patient age or tumor stage at diagnosis or sex. In a population-based study, we associated administration of the cholera vaccine after CRC diagnosis withdecreased risk of death from CRC and overall mortality.

Serum MicroRNA profile in patients with colon adenomas or cancer

BackgroundColon cancer, one of the most common causes of cancer-related deaths, arises from adenomatous polyps. In these years, circulating microRNAs (miRNAs) have attracted increasing attention as novel biomarkers for colon cancers. The dysregulated circulating miRNAs in patients with colon adenomas has not been well-understood.MethodsHere, we aimed to identify miRNA profile in the serum of patients with colon adenomas or colon cancer by using microarray. Then we validated eight differentially expressed miRNAs (DEMs) by qRT-PCR and predicted their targets.ResultsWe identified 26 DEMs from Adenomas versus Normal comparison (11 up-regulations and 15 down-regulations), 72 DEMs from Cancer versus Normal comparison (19 up-regulations and 53 down-regulations) and 17 DEMs from Cancer versus Adenomas comparison (4 up-regulations and 13 down-regulations). Moreover, three DEMs identified from Cancer versus Normal comparison were included in the list of DEMs identified from Cancer versus Adenomas comparison, and may be specific diagnostic biomarkers for colon cancer. Five down-regulated miRNAs identified from Cancer versus Normal comparison were included in the list of DEMs identified from Adenomas versus Normal comparison, and may be important for the development of colon polyps and cancer.ConclusionsWe discovered 8 circulating miRNAs associated with colon adenomas and colon cancer, and these miRNAs may potentially serve as noninvasive screening biomarkers for colon cancer. Our study is useful for expanding our understanding in the development of colon adenomas and colon cancer, and thus provide novel insights into colon cancer pathogenesis and prevention.

P7009 Precancerous molecular features committing development of colonic polyps revealed by studies on the porcine model of human familial adenomatous polyposis

P7009 Precancerous molecular features committing development of colonic polyps revealed by studies on the porcine model of human familial adenomatous polyposis

Abstract A05: Immunity, the colonic environment, and colon cancer

Abstract Background: Colorectal cancer (CRC) is the second leading cause of cancer-associated deaths in the US. Evidence from several studies suggests that the colonic immune environment can influence the risk of CRC. Bacterial minicells (MC) are spherical, non-viable nano-sized particles derived from genetically-engineered E. coli (Vaxiion Therapeutics, Inc). MC contain all of the components of parental bacteria they are derived from with the exception of the chromosome, making them non-infectious. MC used here have been engineered to display antitumor activity via integrin-specific cytotoxic effects but evidence suggests they also require a working immune system to be optimally effective in mouse models of cancer. For our colon cancer studies, we are using an immune-competent mouse model, FABP-CreXApcfl/+, which has a conditional deletion of exons 11-12 in one Adenomatous Polyposis Coli (Apc) allele in the epithelium of colon and distal ileum, due to the targeted expression of CRE, leading to colonic polyposis. Hypothesis: Since MC have been shown to have anti-cancer activity in multiple mouse models, but even more importantly because evidence suggests they are more effective in animals with a functional immune system, we hypothesize that MC can change the immune environment of the colon and delay/decrease the onset of colon cancer in our mouse model. Methods: We treated 14 week old FABP-CreXApcfl/+ mice with PBS or 1.5 x 109 MC in PBS intra-rectally once a week until 19 weeks of age (6 treatments total). Mice were then left untreated until 26 weeks of age, euthanized, and colons were collected to measure tumor number and size. Colonic tumor load was also compared to 24 week old untreated FABP-CreXApcfl/+ controls. RNA was isolated from tumor adjacent (TA), small tumor (≤4mm) and large tumor (&amp;gt;4 mm) tissue, converted to cDNA, and qPCR studies were performed. Hprt was used as a housekeeping gene control and fold-change target gene expression was reported in comparison to Hprt expression. Results: The mean number of colonic polyps in 26 week old mice that received MC-treatment during the 14th-19th week of age was significantly lower (2.4±1.5) in comparison with mice that received PBS only (9.3±1.4, p=0.03) or 24 week-old untreated controls (8.0±1.9, p=0.02). Moreover, MC-treatment significantly restricted the development of colonic polyps &amp;gt;4mm in size (0.6±0.2/mouse, i.e. 60% of mice had one large tumor each) in comparison to PBS-treated (3.7±0.8/mouse, p=0.03) and 24 week-old untreated (2.0±0.2/mouse, p=0.01) controls. Furthermore, as per qPCR studies, preliminary work suggests that MC promote the expression of TH1 and cytotoxic T cell-associated immune responses (CD8a, Tbet, Ifng, perforin) as well as the TH17 (Il17a) immune gene marker in the TA areas of the colon. We also found a decline in the expression of pro-inflammatory (il23, Il6), immunosuppressive (Il10, Foxp3) and immune cell recruitment (Cx3cl1) immune markers in the large tumors of MC-treated mice. Furthermore, our preliminary data suggest the presence of ‘low’ and ‘high’ responders in MC-treated mice. ‘Low responders’ have at least one large tumor at 26 weeks of age and lower correlation of TH1 and cytotoxic T cell-associated immune responses in comparison to ‘high responders’ which have an absence of large tumors and display multi-fold higher levels of TH1 and cytotoxic T cell-associated immune responses in comparison to PBS-treated controls. Conclusion: MC significantly delay the development of colonic polyps and our preliminary data suggest that the delay/decrease in tumorigenesis could be because of attenuation of pro-tumor inflammation as well as promotion of anti-tumor immunity in the colon. These studies also suggest our mouse model will be appropriate for the study of low and high responder anti-tumor immune phenotypes in mice, shedding light on what may be occurring in human CRC patients. Citation Format: Mohammad W. Khan, Shingo Tsuji, MengXi Tian, Nairika Meshgin, Shea Grenier, Matthew J. Giacalone, Kathleen L. McGuire. Immunity, the colonic environment, and colon cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A05.

Synthesis and in vivo evaluation of N-ethylamino-2-oxo-1,2-dihydro-quinoline-3-carboxamide for inhibition of intestinal tumorigenesis in APCMin/+ mice

A selective KGFR tyrosine kinase inhibitor, N-ethylamino-2-oxo-1,2-dihydro-quinoline-3-carboxamide, was synthesized and its possible inhibitory effects on the development of colon polyps and colorectal tumors was examined in APCMin/+ mice, a mouse model of human intestinal familial adenomatous polyposis. The present study shows for the first time that a dietary administration of a selective KGFR tyrosine kinase inhibitor lacks the overt-toxicities and significantly reduced the growth of small intestinal polyps in both male and female APCMin/+ mice. This inhibition of polyp growth appears to occur at a greater extent in female mice.

대장내시경 수검자에서 관찰된 대장용종의 유병률 및 위험인자

본 연구는 검진센터에서 대장내시경을 실시한 무증상 성인들을 중심으로 대장암의 전구병변인 대장용종의 유병률 및 위험인자를 알아보고 무증상의 건강한 성인들에게 대장암 관리를 위한 기초자료를 제공하고자 시행하였다. 2010년 1월부터 12월까지 일개 대학병원 검진센터에서 대장내시경검사를 받은 995명을 대상으로 자기기입식 설문지, 의료기록지, 임상검사 결과지들을 이용하여 후향적으로 시행하였으며, 자료의 분석은 SPSS18.0을 이용하였다. 무증상 성인들의 대장용종 유병률은 남성에서 높았고, 연령대가 높을수록 증가하였다. 남성, 고령, 운동을 하지 않은 경우 독립적인 위험인자로서 대장용종과 밀접한 관련이 있는 것으로 나타났다. 따라서 40대 이상 성인에서는 대장내시경 검사를 통한 대장용종의 조기 발견이 중요하며, 대장암 전구병변인 대장용종의 일차 예방을 위한 지속적인 생활습관 교정 및 운동프로그램 개발이 필요하다. This study was performed to evaluate the prevalence and risk factors of colonic polyps which is an established premalignant lesion and to provide basic data for the management of colon cancer in asymptomatic adults. The subjects of this study were 995 persons who underwent screening colonoscopy between January to December 2010 in health promotion center of an University Hospital located in Busan, and structured questionnaire, medical questionnaire, medical records were reviewed retrospectively. The data were analyzed by SPSS 18.0 program. Colonic polyps were found in 63.2% of the subjects. The prevalence rate of colonic polyps was significantly higher in males and it increased with age. Age, sex and exercise were found to be related independently to colonic polyps. Early detection of colonic polyps by colonoscopy is important for adults over 40 years, and it is necessary to advise such subjects to correct a wrong life-style in order to primarily prevent the development of colonic polyps.

Women who eat fish have fewer colon polyps

Women who eat at least 3 servings of fish per week are less likely to develop some types of colon polyps, according to researchers from the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, in a study published in the American Journal of Clinical Nutrition.1 Lead author Harvey Murff, MD, MPH, and colleagues say that omega-3 fats in fish may reduce inflammation and protect against the development of colon polyps, which can develop into cancer. Although previous animal studies have demonstrated this link, human studies have been inconclusive. More than 5300 individuals were enrolled in the Tennessee Colorectal Polyp Study and underwent colonoscopies. They completed questionnaires to say how often they ate fish, and some participants provided urine samples to be measured for a hormone related to inflammation. Women who ate 3 servings of fish per week had an approximately 33% reduction in the risk of colon polyps. At the same time, they also had a lower level of the hormone prostaglandin E2, which is linked to inflammation and also is known to be associated with adenomas of polyps in colorectal cancers, Dr. Murff notes. Fish oil appears to have effects similar to aspirin in reducing inflammation and thus possibly preventing the formation of polyps, he adds. Men who ate more fish in the study, however, did not have a reduction in the development of colon polyps. Dr. Murff speculated that men may be eating more omega-6 fatty acids, which are found in meats, grains, and in corn, safflower, and sunflower oils, and may counteract the protective effect of omega-3 fatty acids. At the same time, not all fish are high in omega-3 fatty acids. Tuna, salmon, and sardines are, whereas tilapia and catfish are not. Researchers are conducting a clinical trial to determine the effect of fish oil supplementation and prostaglandin E2 production to validate their results. Reference

Metabolic Basis of Obesity

Obesity is a chronic condition that impacts every field of medicine. For the practicing gastroenterologist, the risk for colon cancer as well as colon polyp development and the treatment of gastroesophageal disease are improved by weight reduction. Therefore, understanding the metabolic basis of obesity as well as the management of obesity is a priority for the practicing clinician. The authors of Metabolic Basis of Obesity provide a desktop tool that reviews the pathophysiology of obesity and its associated diseases.

Serum ALT is an Independent Predictor for Polypectomy During Screening Colonoscopy

Background: Diabetes and its antecedent condition, metabolic syndrome, have been associated with an increased risk of development of colon polyps and colorectal carcinoma. Nonalcoholic fatty liver disease (NAFLD) frequently coexists with these conditions and is associated with elevation in serum alanine aminotransferase (ALT). Our aim was to test our apriori hypothesis that after adjusting for currently established predictors of colon polyps, elevated serum ALT will be associated with increased rate of polypectomy. Methods: We conducted retrospective analysis on ten Veterans affairs (VA) VISN representing half of all VA medical centers, obtained from Veterans Affairs Medical SAS Data sets and Decision Support System from 2002 to 2009. We included adult patients without diabetes mellitus between the ages of 45 and 65 receiving first VA documented outpatient screening colonoscopy using validated methods. We excluded patients with human immunodeficiency virus infection, and those with liver disease from hepatitis C or alcohol abuse as well as those with missing values for ALT. Baseline ALT was defined as the ALT level closest to date of colonoscopy and within 12 months of colonoscopy. We categorized ALT levels to 0 to <30 IU/L (referent), 30 to <40, 40 to <50, 50 to <60 and ≥ 60. Based on literature review, we identified the following as established predictors of polyp occurrence: age, male gender, tobacco use, obesity, and use of nonsteroidal anti-inflammatory drugs and conducted logistic regression analysis with these variables in addition to ALT. Results: A total of 43,533 patients met our study criteria, of this 18591 (42.7%) had polypectomy. On adjusted analysis, ALT remained a significant additional predictor of polypectomy (Table). When compared to patients with ALT < 30, we found a linear increase in the rates of polypectomy with adjusted Odds Ratio (OR) of 1.03, 1.13, 1.19 and 1.26 among patient with ALT of 30 to <40, 40 to <50, 50 to <60 and≥ 60 respectively. Conclusions: In this well powered national Veteran cohort, ALT was found to be an independent additional predictor of polypectomy. More importantly, we found a linear relationship between ALT levels and polypectomy. Utilizing ALT as a surrogate for NAFLD, our data provides further support for NAFLD being an independent risk factor for polyp occurrence.

* Substantial chemopreventative effect of piroxicam in min mice independent of peroxisome proliferator activated receptor alpha

IntroductionNon-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have chemopreventative properties against the development of colon polyps and cancer. We have previously shown that peroxisome proliferator activated receptor (PPAR) –...

Frequency of the common germline MUTYH mutations p.G396D and p.Y179C in patients diagnosed with colorectal cancer in Southern Brazil

MUTYH-associated polyposis (MAP) is an autosomal recessive cancer predisposition syndrome associated with the development of colorectal tumors and colonic polyps at an early age. MAP syndrome is associated to germline biallelic mutations in the MUTYH gene which lead to deficient DNA repair through the base-excision repair system and accumulation of G:C→T:A transversions. Occurrence of such mutations in oncogenes and tumor suppressor genes drives colorectal carcinogenesis and is associated with the development of colonic polyps. Two common mutations, p.Y179C and p.G396D, are present in approximately 70-80% of MAP in European families with identified MUTYH germline mutations. The aim of this study was to assess the frequency of the germline MUTYH mutations p.Y179C and p.G396D in Brazilian patients with MAP and other hereditary colorectal cancer (CRC) phenotypes, as well as in sporadic CRC cases. A total of 75 patients were included. Samples were screened for the MUTYH germline mutations p.Y179C and p.G396D by allelic discrimination assays using allele-specific TaqMan® probes. In all mutation-positive cases, results were confirmed by sequencing. Biallelic germline MUTYH mutations were identified in 4 of 60 (6.6%) patients with a phenotype of hereditary colorectal cancer. Germline MUTYH mutation screening should be considered in the differential diagnosis of hereditary colorectal syndromes, and not only in MAP, but also in familial adenomatous polyposis and Bethesda criteria-positive families. Additional mutation screening studies of the MUTYH gene in a larger number of Brazilian patients will be necessary to confirm these results and determine the validity and applicability of MUTYH mutation screening in our population.

Oligodeoxyribozymes That Cleave β-Catenin Messenger RNA Inhibit Growth of Colon Cancer Cells via Reduction of β-Catenin Response Transcription

Abnormal regulation of Wnt/beta-catenin signaling followed by increased levels of the beta-catenin protein have been identified in enhanced cellular proliferation and development of colon polyps and cancers. To inhibit beta-catenin gene expression in colon cancer cells, RNA-cleaving oligodeoxyribozyme (DNAzyme) was employed to destroy the beta-catenin mRNA. We designed a strategy to identify the cleavage sites in beta-catenin RNA with a pool of random sequences from a DNAzyme library and identified four potential DNAzyme-working sites. DNAzymes were constructed for the selected target sites and were tested for the ability to cleave beta-catenin RNA. When introduced into the cells, the selected DNAzymes decreased the expression of beta-catenin significantly as well as its downstream gene, cyclin D1. Additionally, we designed short hairpin RNA that targets the same cleavage site for the selected DNAzyme. The designed short hairpin RNA also inhibited beta-catenin gene expression in colon cancer cells. Our studies show that RNA-cleaving DNAzymes and RNA interference targeted to beta-catenin significantly reduced beta-catenin-dependent gene expression, resulting in inhibition of colon cancer cell growth. These results indicate that the functional antisense oligonucleotides directed against beta-catenin might have potential as a therapeutic intervention to treat colon cancer.

Do Patients Need More Frequent Colonoscopic Surveillance After Liver Transplantation?

Background Solid-organ transplant recipients are at higher risk for developing malignancies believed to be due to the use of immunosuppression. The aim of our study was to determine the risk of development of colon polyps with advanced features and colon carcinoma in liver transplant (LT) recipients when compared to individuals with chronic liver disease (CLD) and individuals without liver disease. Methods Case-control analyses of 82 LT recipients who underwent posttransplant colonoscopy, matched for age, gender, and year of colonoscopy, were compared to 82 patients with chronic liver disease and 82 patients without liver disease undergoing screening colonoscopy. Incidence of advanced adenomas (polyps >1 cm, high-grade dysplasia, villous histology) and colon carcinoma was documented. Results The groups were similar in age and gender, but there were more Hispanic patients in the LT group. Six patients (7.3%) of the LT group, 3 patients (3.6%) of the chronic liver disease group, and 1 patient (1.2%) of the no-liver-disease group had the outcome of interest, but the P value was not significant. Immunosuppression used was tacrolimus and mycophenolate in 2 patients, tacrolimus-only in 2 patients, and cyclosporine in 2 patients. Conclusions There is a trend toward increased incidence of advanced colon polyps and colon carcinoma in immunosuppressed patients after liver transplantation. Larger studies are needed to determine whether posttransplant colon cancer surveillance should be more frequent than currently recommended for nontransplant patients.