Hierarchical contribution of individual lifestyle factors and their interactions on adenomatous and serrated polyp risk.

BACKGROUND: Individual colorectal polyp risk factors are well characterized; however, insights into their pathway-specific interactions are scarce. We aimed to identify the impact of individual risk factors and their joint effects on adenomatous (AP) and serrated polyp (SP) risk. METHODS: We collected information on 363 lifestyle and metabolic parameters from 1597 colonoscopy participants, resulting in over 521,000 data points. We used multivariate statistics and machine-learning approaches to assess associations of single variables and their interactions with AP and SP risk. RESULTS: Individual factors and their interactions showed common and polyp subtype-specific effects. Abdominal obesity, high body mass index (BMI), metabolic syndrome, and red meat consumption globally increased polyp risk. Age, gender, and western diet associated with AP risk, while smoking was associated with SP risk. CRC family history was associated with advanced adenomas and diabetes with sessile serrated lesions. Regarding lifestyle factor interactions, no lifestyle or dietary adjustments mitigated the adverse smoking effect on SP risk, whereas its negative effect was exacerbated by alcohol in the conventional pathway. The adverse effect of red meat on SP risk was not ameliorated by any factor, but was further exacerbated by western diet along the conventional pathway. No modification of any factor reduced the negative impact of metabolic syndrome on AP risk, whereas increased fatless fish or meat substitutes' intake mitigated its effect on SP risk. CONCLUSIONS: Individual risk factors and their interactions for polyp formation along the adenomatous and serrated pathways are strongly heterogeneous. Our findings may facilitate tailored lifestyle recommendations and contribute to a better understanding of how risk factor combinations impact colorectal carcinogenesis.

Fundic gland polyps related to diverse aetiologies show subtle morphological differences: a multicentre retrospective study.

AIMS: Fundic gland polyps (FGPs) comprise 66% of all gastric polyps. Although they are usually non-syndromic, they may be associated with various syndromes, including familial adenomatous polyposis (FAP) or gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). We aimed to evaluate how histological features relate to distinct FGP subtypes. METHODS AND RESULTS: We performed a retrospective analysis of 118 FGPs from 109 patients for the architecture of fundic glands, microcyst lining, parietal cell hyperplasia and surface foveolar epithelial changes. Age, gender and history of FAP or GAPPS were collected. Based on combinations of histological features, three distinct patterns (A, B and C) of FGPs were delineated and correlated to the aetiologies. Non-syndromic FGPs were well-formed polyps composed of disordered fundic glands with intermediate-sized microcysts typically lined by a mixture of oxyntic and mucin-secreting cells (73%). Parietal cell hyperplasia (80%) and foveolar surface hyperplasia (78%) were common. FAP-associated cases demonstrated small microcysts that were predominantly lined by fundic epithelium (77%), with limited parietal cell hyperplasia (27%); foveolar hyperplasia was uncommon. GAPPS-related polyps were the largest, with prominent, mucin-secreting epithelium-lined microcysts (73%). Hyperproliferative aberrant pits were universally present, whereas parietal cell hyperplasia was uncommon. Pattern A was identified in most non-syndromic FGPs (74%) and in a minority of FAP-related FGPs (26%). The majority (82%) of FAP-related FGPs showed pattern B, but only 18% of non-syndromic FGPs did. Pattern C consisted exclusively of GAPPS-associated polyps. CONCLUSIONS: We conclude that, although FGPs share similar histomorphology, subtle differences exist between polyps of different aetiology. In the appropriate clinical setting, the recognition of these variations may help to consider syndromic aetiologies.

Filling the gap: A thorough investigation for the genetic diagnosis of unsolved polyposis patients with monoallelic MUTYH pathogenic variants.

BACKGROUNDS: MUTYH-associated polyposis (MAP) is an autosomal recessive disease caused by biallelic pathogenic variants (PV) of the MUTYH gene. The aim of this study was to investigate the genetic causes of unexplained polyposis patients with monoallelic MUTYH PV. The analysis focused on 26 patients with suspected MAP, belonging to 23 families. Ten probands carried also one or more additional MUTYH variants of unknown significance. METHODS: Based on variant type and on the collected clinical and molecular data, these variants were reinterpreted by applying the ACMG/AMP rules. Moreover, supplementary analyses were carried out to investigate the presence of other variants and copy number variations in the coding and promoter regions of MUTYH, as well as other polyposis genes (APC, NTHL1, POLE, POLD1, MSH3, RNF43, and MCM9). RESULTS: We reclassified 4 out of 10 MUTYH variants as pathogenic or likely pathogenic, thus supporting the diagnosis of MAP in only four cases. Two other patients belonging to the same family showed a previously undetected deletion of the APC gene promoter. No PVs were found in the other investigated genes. However, 6 out of the 18 remaining families are still interesting MAP candidates, due to the co-presence of a class 3 MUTYH variant that could be reinterpreted in the next future. CONCLUSION: Several efforts are necessary to fully elucidate the genetic etiology of suspected MAP patients, especially those with the most severe polyposis/tumor phenotype. Clinical data, tumor molecular profile, family history, and polyposis inheritance mode may guide variant interpretation and address supplementary studies.

Gastritis, Gastric Polyps and Gastric Cancer.

Gastric cancer is still an important disease causing many deaths worldwide, although there has been a marked reduction in prevalence during the last few decades. The decline in gastric cancer prevalence is due to a reduction in Helicobacter pylori infection which has occurred for at least 50 years. The most probable mechanism for the carcinogenic effect of H. pylori is hypergastrinemia since H. pylori infected individuals do not have increased risk of gastric cancer before the development of oxyntic atrophy. When atrophy has developed, the carcinogenic process continues independent of H. pylori. Autoimmune gastritis also induces oxyntic atrophy leading to marked hypergastrinemia and development of ECL cell neoplasia as well as adenocarcinoma. Similarly, long-term treatment with efficient inhibitors of acid secretion like the proton pump inhibitors (PPIs) predisposes to ECL cell neoplasia of a different degree of malignancy. Contrasting the colon where most cancers develop from polyps, most polyps in the stomach have a low malignant potential. Nevertheless, gastric polyps may also give rise to cancer and have some risk factors and mechanisms in common with gastric cancer. In this overview the most common gastric polyps, i.e., hyperplastic polyps, adenomatous polyps and fundic gland polyps will be discussed with respect to etiology and particularly use of PPIs and relation to gastric carcinogenesis.

Serrated polyps: innocent or guilty?

Serrated lesions represent a group of lesions with different genetic and biological features causing important clinical repercussions. Three types of serrated lesions are identified: hyperplastic, sessile adenomas (with and without dysplasia) and traditional serrated adenomas. Such lesions are now recognized as precancerous lesions.The carcinogenic process of serrated lesions follows a pathway including: alterations concerning activation of mitogen and protein kinase regulating the extracellular signal of other intracellular kinases (MAPK-ERK), inhibition of the apoptosis and hypermethylation of DNA and instability of microsatellites. Like for adenomatous polyps, the risk factors for serrated lesions are environmental factors, related to lifestyle and diet. The cancerogenic risk is increased by excessive alcohol consumption, obesity and poor intake of folate. When a high number of colorectal polyps with architecture serrated is diagnosed, it could be considered as serrated polyposis syndrome (SPS). According the most recent ESGE guidelines, the diagnostic criteria of the SPS, are: at least 5 polyps resected proximal to the sigmoid colon, 2 of which> 10 mm, or >20 serrated lesions of any size distributed in the entire colon. This condition presents a high risk for personal and/or familiar CRC, for this reason a regular screening colonoscopy should be performed in these patients and in their first-degree relatives.

Phenotypic variations of gastric neoplasms in familial adenomatous polyposis are associated with endoscopic status of atrophic gastritis.

BACKGROUND AND AIM: Gastric neoplasms (GN), including gastric adenoma and carcinoma, are well known as extracolonic manifestations of familial adenomatous polyposis (FAP). We aimed to investigate the clinicopathological features of GN in FAP patients and to clarify their relationship with the endoscopic status of the background mucosa. METHODS: We analyzed the records of 39 patients who were diagnosed with FAP and underwent esophagogastroduodenoscopy between April 2005 and July 2016. Patients were divided into two groups according to atrophic gastritis (AG) status. Endoscopic findings of GN and background mucosa, and histopathological findings, including phenotypic expression of GN and mutation locus of adenomatous polyposis coli (APC) gene, were evaluated. RESULTS: Gastric neoplasms were more predominant in the AG-positive group than in the AG-negative group (6/9, 66.7% vs 7/30, 23.3%; P = 0.039). Of 36 GN detected in 13 patients, six GN in five patients were followed and 30 GN in eight patients were endoscopically resected and analyzed. GN in the AG-negative group frequently showed whitish color, were located in the proximal stomach, and presented the gastric immunophenotype compared to GN in the AG-positive group. All GN were intramucosal lesions and were curatively resected regardless of AG status. APC germline mutations were identified in 32 patients. In patients with GN, a significantly higher number of mutation loci were among exons 10-15 (codons 564-1465). CONCLUSION: Clinicopathological characteristics and phenotypic expressions of GN in FAP patients depend on background mucosa status with or without AG. These findings are useful for detecting GN in FAP patients.

Fundic gland polyp prevalence according to Helicobacter pylori infection status.

BACKGROUND AND AIM: The prevalence of fundic gland polyp (FGP) occurrence has not been clarified in individuals with Helicobacter pylori infection post-eradicated status. This study was performed to examine the relationship between FGP prevalence and H. pylori infection status. METHODS: We enrolled 3400 subjects (2185 male subjects and 1215 female subjects; mean age 54.7 ± 9.5 years) with known H. pylori infection status and who underwent an upper gastrointestinal endoscopy examination as part of an annual check-up. Subjects without and with H. pylori infection numbered 1617 and 239, respectively, while 1544 had a post-eradication status. The presence of FGP and degree of gastric mucosal atrophy were determined in each subject using an endoscopic method. RESULTS: Endoscopy findings showed FGPs in 1029 (30.3%) of all subjects. The prevalence ratio of FGP positivity in H. pylori-negative, H. pylori-positive, and post-eradicated subjects was 51.9%, 1.7%, and 12.0%, respectively. Multiple logistic regression analysis revealed that female gender, older age, milder gastric mucosal atrophy, and anti-secretory therapy were significant risk factors for FGP occurrence. As compared with H. pylori-positive subjects, the odds ratios for H. pylori-negative and post-eradication status were 48.3 and 6.6, respectively (P < 0.001). In the post-eradication status subjects, longer duration following bacterial eradication was a significant risk factor for occurrence of FGPs. CONCLUSION: The risk of FGP occurrence in individuals who have undergone H. pylori eradication treatment is lower as compared with those who have never been infected. However, that risk increases over time following eradication.

Cronkhite-Canada syndrome causing pouch outlet obstruction 5 years after roux-en-y gastric bypass.

OBJECTIVE: We present the case of a 57-year-old man with a history of Roux-en-Y gastric bypass (RYGB) and colonic polyps who presented with an upper gastrointestinal obstruction based on massive stomach polyposis in the pouch. METHODS: Two months prior to this acute admission, he had undergone resection of the gastric remnant due to massive refractory intraluminal bleeding from a polypoid mass. Ten years earlier, right colectomy was performed due to hypertrophic polyposis unsuitable for endoscopic polypectomy. Upper gastrointestinal endoscopy showed a polypoid mass in the pouch causing obstruction. Benign biopsies were obtained. A resection of the stomach pouch with esophagojejunostomy was performed. Macroscopic evaluation of the pouch lumen showed massive polyposis with a sharp demarcation near the Z-line and at the gastrojejunostomy. On clinical examination, the presence of atrophic nail changes, alopecia, and palmar hyperpigmentation was noticed. RESULTS: Postoperative course was uneventful and feeding was restarted successfully. Histological analysis revealed hyperplastic polypoid tissue, which resembled the polyps in the stomach remnant and colon. Together with the ectodermal changes, the diagnose of Cronkhite-Canada syndrome was established. CONCLUSION: Diffuse polyposis in Cronkhite-Canada syndrome is a rare cause for pouch obstruction after RYGB. Clinical examination should focus on dermatologic findings.

Smoking Habits are Strongly Associated With Colorectal Polyps in a Population-based Case-control Study.

GOALS: The goal of this study is to test the association between lifetime smoking habits and colorectal polyps of different classifications. BACKGROUND: Smoking is an established risk factor for several cancers, including colorectal cancer. However, the association between lifetime smoking habits including intensity, duration, and cessation, and premalignant colorectal polyps is yet to be established. STUDY: A case-control study among 828 consecutive subjects aged 40 to 70 years, undergoing screening or diagnostic colonoscopy. Exclusion criteria were: medically treated diabetes, colectomy, and belonging to colorectal cancer high risk group. Polyps were stratified according to histology (serrated or adenomatous polyp) and location. All participants underwent anthropometric measurements and a structured medical and lifestyle interview. RESULTS: Current-smoking was more strongly associated with increased odds for distal rather than proximal polyps [odds ratio (OR), 4.00; 95% confidence interval (CI), 2.40-6.68 and OR, 2.52; 95% CI, 1.46-4.36, respectively], with serrated-polyps rather than adenomas (OR, 6.36; 95% CI, 2.77-14.57 and OR, 3.01; 1.90-4.74, respectively). All levels of smoking intensity (daily cigarettes) were associated with colorectal polyps. A dose-response association was seen between smoking duration and colorectal polyps. Smoking duration of ≥20 years was strongly associated with distal polyps (OR, 4.01; 95% CI, 1.62-9.84), independently of potential confounders, smoking intensity and years since smoking cessation. All associations were stronger for distal serrated polyps. CONCLUSIONS: Smoking duration is associated with colorectal plyps, independently of other potential confounders, smoking intensity, and cessation. The association is stronger with distal rather than proximal polyps, and with serrated polyps rather than adenomas.

BMI1 and MEL18 Promote Colitis-Associated Cancer in Mice via REG3B and STAT3.

BACKGROUND & AIMS: Polycomb group proteins are epigenetic factors that silence gene expression; they are dysregulated in cancer cells and contribute to carcinogenesis by unclear mechanisms. We investigated whether BMI1 proto-oncogene, polycomb ring finger (BMI1), and polycomb group ring finger 2 (PCGF2, also called MEL18) are involved in the initiation and progression of colitis-associated cancer (CAC) in mice. METHODS: We generated mice containing floxed alleles of Bmi1 and/or Mel18 and/or Reg3b using the villin-Cre promoter (called Bmi1ΔIEC, Mel18ΔIEC, DKO, and TKO mice). We also disrupted Bmi1 and/or Mel18 specifically in intestinal epithelial cells (IECs) using the villin-CreERT2-inducible promoter. CAC was induced in cre-negative littermate mice (control) and mice with conditional disruption of Bmi1 and/or Mel18 by intraperitoneal injection of azoxymethane (AOM) followed by addition of dextran sulfate sodium (DSS) to drinking water. Colon tissues were collected from mice and analyzed by histology and immunoblots; IECs were isolated and used in cDNA microarray analyses. RESULTS: Following administration of AOM and DSS, DKO mice developed significantly fewer polyps than control, Bmi1ΔIEC, Mel18ΔIEC, Reg3bΔIEC, or TKO mice. Adenomas in the colons of DKO mice were low-grade dysplasias, whereas adenomas in control, Bmi1ΔIEC, Mel18ΔIEC, Reg3bΔIEC, or TKO mice were high-grade dysplasias with aggressive invasion of the muscularis mucosa. Disruption of Bmi1 and Mel18 (DKO mice) during late stages of carcinogenesis significantly reduced the numbers of large adenomas and the load of total adenomas, reduced proliferation, and increased apoptosis in colon tissues. IECs isolated from DKO mice after AOM and DSS administration had increased expression of Reg3b compared with control, Bmi1ΔIEC, or Mel18ΔIEC mice. Expression of REG3B was sufficient to inhibit cytokine-induced activation of STAT3 in IECs. The human REG3ß protein, the functional counterpart of mouse REG3B, inhibited STAT3 activity in human 293T cells, and its expression level in colorectal tumors correlated inversely with pSTAT3 level and survival times of patients. CONCLUSIONS: BMI1 and MEL18 contribute to the development of CAC in mice by promoting proliferation and reducing apoptosis via suppressing expression of Reg3b. REG3B negatively regulates cytokine-induced activation of STAT3 in colon epithelial cells. This pathway might be targeted in patients with colitis to reduce carcinogenesis.

Intake of dietary fibre and lifetime non-steroidal anti-inflammatory drug (NSAID) use and the incidence of colorectal polyps in a population screened for colorectal cancer.

BACKGROUND: There is suggestive evidence that increased intake of dietary fibre and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are generally associated with decreased colorectal cancer risk. However, the effects on precursors of colorectal cancer, such as adenomatous polyps, are mixed. We present the associations between dietary fibre intake and NSAID use on the presence and type of colorectal polyps in a screening population. METHODS: A cross-sectional study of 2548 individuals undergoing colonoscopy at the Forzani & MacPhail Colon Cancer Screening Centre (Calgary, Canada) was conducted. Dietary fibre intake and NSAID use were assessed using the Diet History Questionnaire I or II and the Health and Lifestyle Questionnaire. Colorectal outcomes were documented as a polyp or high-risk adenomatous polyp (HRAP; villous histology, high-grade dysplasia, ≥10 mm or ≥3 adenomas). Crude and ORs and 95% CIs were estimated using unconditional logistic regression. RESULTS: There were 1450 negative colonoscopies and 1098 patients with polyps, of which 189 patients had HRAPs. Total dietary fibre intake was associated with a decreased presence of HRAPs (OR=0.50, 95% CI: 0.29 to 0.86) when comparing the highest to lowest quartiles and was observed with both soluble (OR=0.51, 95% CI: 0.30 to 0.88) and insoluble (OR=0.51, 95% CI: 0.30 to 0.86) fibres. Ever use of NSAIDs was also inversely associated with HRAPs (OR=0.65, 95% CI: 0.47 to 0.89), observed with monthly (OR=0.60, 95% CI: 0.37 to 0.95) and daily (OR=0.53, 95% CI: 0.32 to 0.86) use. CONCLUSIONS: Dietary fibre intake and NSAID use were associated with a decreased risk of having a HRAP at screening.

Sex-influenced association of non-alcoholic fatty liver disease with colorectal adenomatous and hyperplastic polyps.

AIM: To investigate the relationship between non-alcoholic fatty liver disease (NAFLD) and colorectal adenomatous and hyperplastic polyps. METHODS: A retrospective cross-sectional study was conducted on 3686 individuals undergoing health checkups (2430 males and 1256 females). All subjects underwent laboratory testing, abdominal ultrasonography, colonoscopy, and an interview to ascertain the baseline characteristics and general state of health. Multinomial logistic regression analysis was performed to examine the association between NAFLD and the prevalence of colorectal adenomatous and hyperplastic polyps. Furthermore, the relationship was analyzed in different sex groups. Subgroup analysis was performed based on number, size, and location of colorectal polyps. RESULTS: The prevalence of colorectal polyps was 38.8% in males (16.2% for adenomatous polyps and 9.8% for hyperplastic polyps) and 19.3% in females (8.4% for adenomatous polyps and 3.9% for hyperplastic polyps). When adjusting for confounding variables, NAFLD was significantly associated with the prevalence of adenomatous polyps (OR = 1.28, 95%CI: 1.05-1.51, P < 0.05) and hyperplastic polyps (OR = 1.35, 95%CI: 1.01-1.82, P < 0.05). However, upon analyzing adenomatous and hyperplastic polyps in different sex groups, the significant association remained in males (OR = 1.53, 95%CI: 1.18-2.00, P < 0.05; OR = 1.42, 95%CI: 1.04-1.95, P < 0.05) but not in females (OR = 0.44, 95%CI: 0.18-1.04, P > 0.05; OR = 1.18, 95%CI: 0.50-2.78, P > 0.05). CONCLUSION: NAFLD is specifically associated with an increased risk of colorectal adenomatous and hyperplastic polyps in men. However, NAFLD may not be a significant factor in the prevalence of colorectal polyps in women.

Gastric Hyperplastic Polyps Associated with Proton Pump Inhibitor Use in a Case without a History of Helicobacter pylori Infection.

A 56-year-old man with gastroesophageal reflux disease (GERD) was referred to our hospital. Esophagogastroduodenoscopy (EGD) revealed no evidence of any polypoid lesions in the stomach, and the patient had no history of Helicobacter pylori infection. He received omeprazole (20 mg) once daily for the GERD. EGD was performed at 1 year after the start of omeprazole administration, and this time, gastric hyperplastic polyps (GHPs) were detected. The GHPs increased in size as the omeprazole treatment continued, but they markedly decreased in size following omeprazole discontinuation. Thus, the administration of proton pump inhibitors may be a risk factor for the development of GHP independent of H. pylori infection.

Folic Acid Supplementation in Postpolypectomy Patients in a Randomized Controlled Trial Increases Tissue Folate Concentrations and Reduces Aberrant DNA Biomarkers in Colonic Tissues Adjacent to the Former Polyp Site.

BACKGROUND: Low folate status is associated with an increased risk of colorectal carcinogenesis. Optimal folate status may be genoprotective by preventing uracil misincorporation into DNA and DNA hypomethylation. Adenomatous polyps have low folate status compared with normal colonic mucosa, and they are surrounded by histologically normal mucosa that also is of low folate status. OBJECTIVE: In a randomized controlled trial conducted at a single Dublin hospital between April 2002 and March 2004, we assessed the effect of folic acid supplementation on tissue folate, uracil misincorporation into DNA, and global DNA hypomethylation in colonocytes isolated from sites of adenomatous polyps and from histologically normal tissue adjacent and 10-15 cm distal to them. METHODS: Twenty patients with adenomatous polyps on initial colonoscopy and polypectomy were randomly assigned to receive either 600 µg folic acid/d [n = 12, 38% men, mean age 64.3 y, and body mass index (BMI, in kg/m(2)) 26.6] or placebo (n = 8, 50% men, mean age 68.4 y, and BMI 27.2) for 6 mo, and then repeat the colonoscopy. Blood and colonocyte tissue folate concentrations were measured with the use of a microbiological assay. Uracil misincorporation and global DNA hypomethylation were measured in colonocytes with the use of modified comet assays. RESULTS: Over time, folic acid supplementation, compared with placebo, increased tissue folate (mean ± SEM) from 15.6 ± 2.62 pg/10(5) cells to 18.1 ± 2.12 pg/10(5) cells (P < 0.001) and decreased the global DNA hypomethylation ratio from 1.7 ± 0.1 to 1.0 ± 0.1 (P < 0.001). The uracil misincorporation ratio decreased by 0.5 ± 0.1 for the site adjacent to the polyp over time (P = 0.05). CONCLUSION: A response to folic acid supplementation, which increased colonocyte folate and improved folate-related DNA biomarkers of cancer risk, was seen in the participants studied. Exploratory analysis points toward the area formerly adjacent to polyps as possibly driving the response. That these areas persist after polypectomy in the absence of folate supplementation is consistent with a potentially carcinogenic field's causing the appearance of the polyp.

Does the Presence of Endometrial Polyp Predict Colorectal Polyp?

INTRODUCTION: Endometrial polyps (EPs) and colorectal polyps (CPs) are common disorders and the incidence of both increase rapidly with aging. CPs are focal lesions and incidence increases with age. AIM: In this study, we aimed to analyze retrospectively the relationship between the EPs and CPs sharing similar clinical and genetic factors in their etiopathogenesis. MATERIALS AND METHODS: This study was retrospectively performed between 2010 and 2013 and it included patients diagnosed to have eEPs. The study group and the control group consisted of patients who were diagnosed with or without EPs and who underwent colonoscopy at the same period. RESULTS: The study group was formed by 57 patients with diagnosis of EP who underwent colonoscopy during the same period. The control group consisted of 71 patients without EP examined with colonoscopy. Among 128 patients assessed in this study, 24 were diagnosed with CPs, all of which were adenomatous polyps smaller than 1cm. No hyperplastic or inflammatory polyps were diagnosed. While 18 of 57 patients with EPs had CPs, 6 of 71 control subjects had CPs. Hence, the risk of having CP was 5 times greater in patients with EP compared to those without (P < 0.05). CONCLUSION: The present study demonstrated that the prevalence of CPs increased significantly in postmenopausal patients with EPs. Recommending colonoscopy to these patients irrespective of age may be beneficial for detecting more CPs and preventing colorectal cancer.

Rarity of adenomatous polyps in ulcerative colitis and its implications for colonic carcinogenesis.

BACKGROUND AND STUDY AIMS: Despite ample research on the dysplasia to carcinoma risk in ulcerative colitis, there are scant data on the prevalence of adenomatous polyps in this population. METHODS: The number and histology of all polyps detected at colonoscopies of ulcerative colitis patients aged > 50 during 2006 - 2012 were compared with similarly aged controls undergoing screening colonoscopy. RESULTS: There were 206 patients with ulcerative colitis and 624 controls included in the study (mean age 61.7 ±â€Š8.7 vs. 60.8 ±â€Š6.1, respectively; P = 0.15). Adenomatous polyps were detected in only 13/206 colonoscopies for ulcerative colitis compared with 162 /624 controls (6.3 % vs. 25.9 %, respectively; odds ratio [OR] 0.19, 95 % confidence interval [CI] 0.1 - 0.34; P < 0.0001). When also considering all prior colonoscopies performed over 7.7 ±â€Š4.6 years of follow-up (mean 4.1 ±â€Š2.9 colonoscopies/patient, range 1 - 15, total 832 colonoscopies), the risk of ever finding an adenoma in ulcerative colitis patients was still significantly lower compared with controls (14.1 % vs. 25.9 %, respectively; OR 0.47, 95 %CI 0.3 - 0.72; P = 0.0005). On multivariable analysis, adenomas were positively associated with advanced age (OR 1.07/year, 95 %CI 1.03 - 1.1; P < 0.0001) and with increasing body mass index (BMI; OR 1.06/kg/m(2), 95 %CI 1.01 - 1.1; P = 0.01) and negatively associated with having ulcerative colitis (OR 0.15, 95 %CI 0.09 - 0.44; P = 0.0005). Among 115 Crohn's disease patients aged > 50 years, the rate of ever-adenomas in small-bowel Crohn's disease was similar to the controls (P = 0.8) and not influenced by 5-aminosalicylic acid use, whereas patients with colonic Crohn's disease had a significantly lower rate of adenomas compared with the controls (3.9 % vs. 25.9 %; P = 0.002). CONCLUSION: Unlike patients with small-bowel Crohn's disease, patients with ulcerative colitis or with colonic Crohn's disease seldom develop sporadic adenomatous polyps. These data may provide novel clues to a possible role for colonic immune activation in restricting the adenoma to carcinoma sequence while propagating the dysplasia to carcinoma pathway.