			Home About us Contact

Colorectal Adenomas (colorectal + adenoma)

Distribution by Scientific Domains

Medical Sciences	97%

Distribution within Medical Sciences

Gastroenterology & Hepatology	43%
Oncology & Radiotherapy	35%
4 Other Subdomains	22%

Selected Abstracts

Insulin-like Growth Factor (IGF)-I, IGF-binding Protein-3 and Colorectal Adenomas in Japanese Men

CANCER SCIENCE, Issue 11 2002
Satoshi Teramukai
Several epidemiological studies have found that high levels of plasma insulin-like growth factor (IGF)-I and low levels of IGF-binding protein (IGFBP)-3 are related to an increased risk of colorectal cancer or late-stage adenomas. We examined the relation of body mass index, fasting and 2-h postload plasma glucose levels and plasma concentrations of IGF-I and IGFBP-3 to colorectal adenomas in middle-aged Japanese men. The study subjects comprised 157 cases of histologically diagnosed colorectal adenomas and 311 controls with normal colonoscopy or non-polyp benign lesions in a consecutive series of 803 men receiving a preretirement health examination at two hospitals of the Self Defense Forces (SDF). After adjustment for rank in the SDF, hospital, smoking and IGFBP-3, a statistically nonsignificant modest increase in the prevalence odds of colorectal adenomas was observed for the highest versus the lowest quartile level of IGF-I. The increase was slightly greater with further adjustment for 2-h glucose concentrations (adjusted odds ratio 1.8, 95% confidence interval 1.0,4.5, trend P=0.06). Men with high levels of IGFBP-3 showed only a minimal decrease in risk after adjustment for IGF-I. The association with IGF-I was less evident for advanced adenomas (,5 mm in size or tubulovillous/villous). Fasting and 2-h glucose and body mass index were more strongly positively associated with colorectal adenomas than IGF-I, especially with advanced adenomas, independently of IGF-I and IGFBP-3. The findings suggest that plasma IGF-I and IGFBP-3 may be involved in colorectal tumorigenesis regardless of the stage in growth of adenoma, but not as a mediator for the effects of being overweight or of hyperglycemia. [source]

Distribution trends of colorectal adenoma and cancer: A colonoscopy database analysis of 11 025 Chinese patients

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2010
Yu Bai
Abstract Background and Aim:, A left-to-right shift of colorectal cancer (CRC) has been reported in Western studies. However, few Asian studies have investigated the anatomic distribution of colorectal adenoma and CRC. We aimed to describe the time trends in the distribution of colorectal adenoma and CRC in a Chinese population. Methods:, A colonoscopy database was reviewed, and all consecutive patients with lower gastrointestinal symptoms who underwent colonoscopy from 1998 to 2009 were identified. Data, including patients' sex, age, symptoms, and the number and anatomic locations of colorectal adenoma and CRC, were documented. Results:, A total of 11 025 patients were included in the final analysis; 1012 and 363 patients were diagnosed with colorectal adenoma and CRC, respectively. Overall, there were more distal than proximal adenomas (54.4% vs 37.9%), and the proportion of proximal adenomas remained stable from 1998,2006 to 2007,2009 (38.2% vs 37.6%). Similarly, there were more distal than proximal CRC (56.5% vs 42.4%), and the proportion of proximal CRC declined from 45.8% in 1998,2006 to 38.4% in 2007,2009. Colorectal adenoma and CRC were equally distributed among both sexes. For elderly patients (> 50 years), there was a non-significant trend towards more proximal adenoma and CRC. Conclusions:, The present study suggests no distal-to-proximal shift of colorectal adenoma and CRC among the Chinese population in Shanghai over the past 12 years. The distribution pattern of colorectal adenoma and CRC of Chinese patients is different from that of Western patients, who had more colorectal lesions located in the distal part. [source]

DNA methylation patterns in adenomas from FAP, multiple adenoma and sporadic colorectal carcinoma patients

INTERNATIONAL JOURNAL OF CANCER, Issue 4 2006
Coral V.A. Wynter
Abstract Colorectal adenomas have traditionally been regarded as homogeneous. The aim of our study was to identify molecular features that may differentiate sporadic adenomas from familial adenomas such as Familial Adenomatous Polyposis (FAP) and Multiple Adenoma patients. DNA methylation was tested at Methylated IN Tumor (MINT) loci (1,2,12,31) and the CpG promoter region of genes MLH1, HPP1, MGMT, p14ARF and p16INK4a in FAP-associated adenomas (33) from 5 patients with a known APC mutation (Group 1, FAP), adenomas (29) from 4 Multiple Adenoma patients (Group 2 Multiple), adenomas (14) from 3 patients with sporadic colorectal cancers showing high microsatellite instability (Group 3, MSI-H) and adenomas (16) from 7 patients, with sporadic colorectal cancers showing microsatellite stable or low level instability (Group 4, MSS/MSI-L). Aberrant Crypt Foci (ACFs), Hyperplastic Polyps (HPs) and cancers were also examined for methylation status as well as K- ras mutation. Multiple Adenoma patients were examined for germline polymorphisms in the base excision repair gene, MYH. The familial syndrome, FAP -associated adenomas showed a significantly low frequency of MINT methylation (15.5%,) compared to sporadic MSS/MSI-L-associated adenomas (35.5%). Group 3 (MSI-H) adenomas were different in that many showed serration and a high level of methylation (57.1%). Group 2, Multiple Adenoma cases, resembled sporadic MSS/MSI-L-associated adenomas. However the promoter regions of key genes, MGMT, p14ARF and p16INK4a were methylated to a greater extent than MINTs in both sporadic and familial adenomas. Genetic profiling of adenomas supports the concept that adenomas belonging to familial syndromes pursue a different pathway to tumorigenesis than their sporadic counterpar/ts from their earliest formation. © 2005 Wiley-Liss, Inc. [source]

The Vienna classification applied to colorectal adenomas

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2006
Carlos A Rubio
Abstract Background and Aim:, In 1999, a group of Western and Asian pathologists gathered in Vienna reached consensus regarding the classification of gastrointestinal epithelial neoplasia. In this study, that classification is applied to colorectal adenomas. Methods:, Colorectal adenomas from 1552 patients were histologically classified according to the categories listed in Vienna: category 3, low-grade dysplasia; 4.1, high-grade dysplasia; 4.2, carcinoma in situ; 4.3, suspicious of intramucosal carcinoma; 5.1, intramucosal carcinoma; and 5.2, submucosal carcinoma. The criteria used to diagnose these lesions are described in detail. Adenomas with dysplasia (categories 3 and 4.1) or with carcinoma (categories 4.2, 4.3, 5.1 and 5.2) were analyzed separately. On basis of their configuration, adenomas were classified into tubular, tubulovillous, villous, serrated, microtubular and combined phenotypes (i.e. other than tubulovillous). Results:, The highest percentage of adenomas with carcinoma was found amongst villous adenomas (29.6%), followed by combined adenomas (27.8%). Villous adenoma with carcinoma was the most frequent neoplasia at all ages; combined adenomas with carcinoma were more frequent among younger patients. In elderly patients (,60 years of age) the highest percentage of adenomas with carcinoma was recorded in villous adenomas (28.1%), followed by serrated adenomas (19.2%). Villous adenomas and combined adenomas with carcinoma were more frequent in males. Conclusion:, The Vienna classification of colorectal adenomas seems to be influenced by parameters inherent to the patient such as age and sex and by the histological phenotype of the adenoma. With the recent improvement in medical technology it is possible to laser-microdisect a defined group of neoplastic glands (such as with carcinoma in situ or with intramucosal carcinoma) for specific molecular analysis. This modern technology will permit in future the translation of histological structures into molecular terms. [source]

Polymorphisms in PTGS1, PTGS2 and IL-10 do not influence colorectal adenoma recurrence in the context of a randomized aspirin intervention trial

INTERNATIONAL JOURNAL OF CANCER, Issue 9 2007
Richard A. Hubner
Abstract Regular use of aspirin and other nonsteroidal antiinflammatory drugs reduces both the development of colorectal neoplasia and recurrence of colorectal adenoma (CRA). Modulation of the effects of aspirin by genetic factors has been reported, potentially allowing targeting of treatment to individuals most likely to gain benefit. Prostaglandin H synthase 1 (PTGS1) and PTGS2 are key enzymes in prostaglandin synthesis and are inhibited by aspirin, whilst interleukin-10 (IL-10) is an important antiinflammatory cytokine. We investigated whether functional genetic polymorphisms in the PTGS1, PTGS2 and IL-10 genes influence CRA recurrence in individuals participating in a randomized aspirin intervention trial. DNA was available for genotyping from 546 patients who received aspirin (300 mg daily) or placebo for a mean 41-months' duration. Homozygote carriers of variant alleles for the PTGS1 50C>T, PTGS2 ,765G>C and IL-10 ,592C>A polymorphisms did not have a significantly altered risk of CRA recurrence (relative risk [RR] = 0.91; 95% confidence interval [CI]: 0.14,6.07, RR = 1.32; 95%CI: 0.66,2.62 and RR = 1.24; 95% CI: 0.74,2.07, respectively). There were also no significant interactions between aspirin intervention and genotype in determining recurrence risk. These data indicate that these polymorphisms are unlikely to influence CRA recurrence and cannot be used to identify individuals who derive benefit from aspirin intervention. © 2007 Wiley-Liss, Inc. [source]

Distribution trends of colorectal adenoma and cancer: A colonoscopy database analysis of 11 025 Chinese patients

Prevalence and risk of colorectal adenoma in asymptomatic Koreans aged 40,49 years undergoing screening colonoscopy

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2010
Su Jin Chung
Abstract Background and Aim:, Colorectal cancer screening is recommended for average-risk persons beginning at age 50. However, information about the incidence and risk factors of precursor adenoma in preceding decades is limited. The aim of this study was to determine the prevalence and risk factors of colorectal adenoma in persons aged 40,49 years and to compare the data with those aged 30,39 years and 50,59 years. Methods:, A cross-sectional study of 5254 asymptomatic subjects who underwent screening colonoscopy was conducted. Data were stratified by age into three groups: 608 aged 30,39 years, 1930 aged 40,49 years, and 2716 aged 50,59 years. Results:, Prevalence of overall adenomas was 10.4% in the 30,39 years age group, 22.2% in the 40,49 years age group, and 32.8% in the 50,59 years age group. Advanced adenoma was found in 0.7% of the 30,39 years age group, 2.7% of the 40,49 years age group, and 4.1% of the 50,59 years age group. In the 40,49 years age group, male sex and current smoking habits showed associations with low-risk adenoma after multiple adjustments. Moreover, male sex (odds ratio [OR] = 1.55, 95% confidence interval [CI]: 1.02,3.23), current smoking (OR = 1.58, 95%CI: 1.06,3.50), and family history of colorectal cancer (OR = 2.54, 95%CI: 1.16,5.56) were independent predictors of advanced adenoma in this age group. Conclusions:, Prevalence of adenoma in subjects aged 40,49 years was higher than in previous studies. Male sex and current smoking habits along with a family history of colorectal cancer were associated with advanced adenoma in this age group. [source]

Dendritic cell infiltration pattern along the colorectal adenoma-carcinoma sequence,

APMIS, Issue 6 2008
APING YUAN
We have previously reported that the dendritic cell (DC) functional index cytokine interleukin-12 was significantly decreased in colorectal carcinoma (CRC) tissues. In this study, the DC infiltration pattern and the density of mature DCs (mDCs; labeled by anti-CD83 and anti-CD208) and immature DCs (iDCs; labeled by anti-CD1,) were characterized using immunohistochemistry (IHC) in tissue samples from 23 patients with CRC, 33 patients with colorectal adenoma (CRA), and 19 healthy controls. In addition, the DC function inhibitor cyclooxygenase-2 (COX-2) and the downstream signal molecule prostaglandin E2 (PGE2) and related receptors EP2/EP4 were measured by quantitative real-time PCR and double immunofluorescence staining. The IHC analyses revealed changed densities of mDCs and iDCs in the tumor microenvironment; in CRA and CRC, the density of mDCs was decreased, but the density of iDCs was gradually increased. Furthermore, the distribution patterns of DCs were also altered. In CRA, mDCs were abundantly distributed in the subepithelial stroma of the adenomatous mass. In CRC, the distribution of mDCs in the tumor stroma was not homogeneous, and mDCs residing in the stroma at invading edges were more frequently found compared with in the intratumoral stroma (P<0.05). Increased iDCs were found in the intratumoral mass in CRC, and some infiltrated into the malignant epithelium. By quantitative real-time PCR, a gradually increased level of COX-2 mRNA was demonstrated in the local tissues along the adenoma-carcinoma sequence, and double immunofluorescence staining showed a colocalization of PGE2 receptors EP2/EP4 with mDCs in the stroma of CRC. In conclusion, our current findings revealed an altered DC infiltration pattern along the adenoma-carcinoma sequence; gradually increased COX-2 expression might contribute to the DC functional defect. [source]

Haplotype-Based Regression Analysis and Inference of Case,Control Studies with Unphased Genotypes and Measurement Errors in Environmental Exposures

BIOMETRICS, Issue 3 2008
Iryna Lobach
Summary It is widely believed that risks of many complex diseases are determined by genetic susceptibilities, environmental exposures, and their interaction. Chatterjee and Carroll (2005, Biometrika92, 399,418) developed an efficient retrospective maximum-likelihood method for analysis of case,control studies that exploits an assumption of gene,environment independence and leaves the distribution of the environmental covariates to be completely nonparametric. Spinka, Carroll, and Chatterjee (2005, Genetic Epidemiology29, 108,127) extended this approach to studies where certain types of genetic information, such as haplotype phases, may be missing on some subjects. We further extend this approach to situations when some of the environmental exposures are measured with error. Using a polychotomous logistic regression model, we allow disease status to have K+ 1 levels. We propose use of a pseudolikelihood and a related EM algorithm for parameter estimation. We prove consistency and derive the resulting asymptotic covariance matrix of parameter estimates when the variance of the measurement error is known and when it is estimated using replications. Inferences with measurement error corrections are complicated by the fact that the Wald test often behaves poorly in the presence of large amounts of measurement error. The likelihood-ratio (LR) techniques are known to be a good alternative. However, the LR tests are not technically correct in this setting because the likelihood function is based on an incorrect model, i.e., a prospective model in a retrospective sampling scheme. We corrected standard asymptotic results to account for the fact that the LR test is based on a likelihood-type function. The performance of the proposed method is illustrated using simulation studies emphasizing the case when genetic information is in the form of haplotypes and missing data arises from haplotype-phase ambiguity. An application of our method is illustrated using a population-based case,control study of the association between calcium intake and the risk of colorectal adenoma. [source]

Genetic polymorphisms of cyclooxygenase-2 and colorectal adenoma risk: The Self Defense Forces Health Study

CANCER SCIENCE, Issue 3 2008
Naoyuki Ueda
Cyclooxygenase (COX) is a key enzyme in the formation of prostaglandins, and an inducible isoform of COX, COX-2, has been implicated in colorectal carcinogenesis. This study investigated the relation of COX-2 polymorphisms (,1195G>A, ,765G>C and 8160A>G) to colorectal adenomas in a case,control study of male officials in the Self Defense Forces (SDF). The study subjects were 455 cases of colorectal adenoma and 1052 controls with no polyps who underwent total colonoscopy. Genotypes were determined using the polymerase chain reaction,restriction fragment length polymorphism (PCR-RFLP) method with genomic DNA extracted from the buffy coat. Statistical adjustment was made for age, hospital, rank in the SDF, body mass index (BMI), cigarette smoking, and alcohol intake. A statistically non-significant decrease in the risk of colorectal adenomas was observed for the AA versus GG genotype of ,1195G>A polymorphism and for the GC versus GG genotype of ,765G>C polymorphism. None had the ,765CC genotype in either the case or control groups. No effect modification of overweight, smoking or alcohol use was observed for either ,1195G>A or ,765G>C polymorphism. The variant allele of the 8160A>G polymorphism was extremely rare. A haplotype of ,1195G, ,765G and 8160A alleles was associated with a modest increase in the risk (adjusted odds ratio [OR] 1.38, 95% confidence interval [CI] 0.99,1.91), and the increase was more evident for distal adenomas (adjusted OR 1.57, 95% CI 1.04,2.38). Another haplotype of ,1195A, ,765C and 8160A alleles showed an adjusted OR of 0.22 (95% CI 0.06,0.88). These findings add to evidence for the role of COX-2 in colorectal carcinogenesis and warrant further studies focusing on haplotypes. (Cancer Sci 2008; 99: 576,581) [source]

ENDOSCOPIC SUBMUCOSAL DISSECTION IN THE UPPER GASTROINTESTINAL TRACT: PRESENT AND FUTURE VIEW OF EUROPE

DIGESTIVE ENDOSCOPY, Issue 2009
Horst Neuhaus
In Western countries endoscopic mucosal resection (EMR) has been widely accepted for treatment of early Barrett`s neoplasia and flat or depressed colorectal adenomas. In contrast endoscopic submucosal dissection (ESD) is infrequently performed for several reasons. It seems to be difficult to overcome the learning curve of this difficult technique because of the low case volume of early gastric cancer. On the other hand ESD of esophageal or colorectal lesions is even more challenging and is considered to be inappropriate for learning. In addition the indication for esophageal or colorectal ESD is controversial in view of excellent results of the well established EMR technique which is less time-consuming and safer than ESD. A recent survey of leading Western endoscopy centers indicated the limited experience with ESD with a low number of cases for all potential indications. Only a few training courses have been established and the number of ongoing clinical studies is limited. Only 12 out of 340 published articles on "endoscopic mucosal dissection" were reported from Western countries. A better acceptance of ESD requires improvement of the technique to allow an easier, faster and safer approach. There is a strong demand for structured training courses and limitations of human cases to selected centers which participate in prospective trials. A close collaboration between Western and Asian centers is recommended for improvement of the ESD technique and its clinical application. [source]

Diagnosis of invasion depth in early colorectal carcinoma by pit pattern analysis with magnifying endoscopy

DIGESTIVE ENDOSCOPY, Issue 2001
Shinji Tanaka
Background: The aim of this study was to clarify whether various pit patterns on the surface of colorectal tumors are associated with various levels of submucosal invasion. Methods: We examined pathologic features of the pit pattern of the tumor surface in 457 colorectal adenomas and early carcinomas. The examinations involved the use of magnifying endoscopy with indigocarmine dye spraying or crystal violet staining methods. Regarding the pit pattern classification, we used the types I, II, IIIL, IIIS, IV, VA and VN. We subclassified the VN pit pattern according to the area of the tumor surface covered into grades A (small), B (medium) and C (large). Results: Magnifying colonoscopic observation revealed the rates of submucosal invasion associated with specific pit patterns to be 1% (3/213) for IIIL, 5% (2/42) for IIIS, 8% (4/57) for IV, 14% (13/93) for VA and 80% (42/52) for VN. The rates of submucosal massive invasion (> 400 ,m) associated with specific pit patterns was 0% (0/213) for IIIL, 0% (0/42) for IIIS, 4% (2/57) for IV, 5% (5/93) for VA and 72% (38/52) for VN. Within the VN pit pattern subclassification, the incidence of submucosal invasion , 1500 ,m was found each grade (A, B & C): 5% (1/19) for grade A, 64% (14/22) for grade B and 93% (13/14) for grade C. Conclusion: Determination of pit pattern is useful for prediction of submucosal invasion depth and for decisions concerning treatment in colorectal tumors. Lesions with VA and non-grade C VN pit patterns are candidates for total endoscopic resection. A grade C VN pit pattern is a definite indicator of severely invasive submucosal carcinoma, which is unresectable by endoscopic resection. [source]

Analysis of somatic APC mutations in rare extracolonic tumors of patients with familial adenomatous polyposis coli

GENES, CHROMOSOMES AND CANCER, Issue 2 2004
Hendrik Bläker
Patients with familial adenomatous polyposis coli (FAP) carry heterozygous mutations of the APC gene. At a young age, these patients develop multiple colorectal adenomas that consistently display a second somatic mutation in the remaining APC wild-type allele. Inactivation of APC leads to impaired degradation of ,-catenin, thereby promoting continuous cell-cycle progression. The role of APC inactivation in rare extracolonic tumors of FAP patients has not been characterized sufficiently. Among tissue specimen from 174 patients with known APC germ-line mutations, we identified 8 tumors infrequently seen in FAP. To investigate the pathogenic role of APC pathway deregulation in these lesions, they were analyzed for second-hit somatic mutations in the mutational cluster region of the APC gene. Immunohistochemistry was performed to compare the expression pattern of ,-catenin to the mutational status of the APC gene. Exon 3 of the ,-catenin gene (CTNNB1) was analyzed for activating mutations to investigate alternative mechanisms of elevated ,-catenin concentration. Although CTNNB1 mutations were not observed, second somatic APC mutations were found in 4 of the 8 tumors: a uterine adenocarcinoma, a hepatocellular adenoma, an adrenocortical adenoma, and an epidermal cyst. These tumors showed an elevated concentration of ,-catenin. No APC mutations were seen in focal nodular hyperplasia of the liver, angiofibrolipoma, and seborrheic wart. This is the first study reporting second somatic APC mutations in FAP-associated uterine adenocarcinoma and epidermal cysts. Furthermore, our data strengthen a role for impaired APC function in the pathogenesis of adrenal and hepatic neoplasms in FAP patients. © 2004 Wiley-Liss, Inc. [source]

Increased expression of fatty acid synthase in human aberrant crypt foci: Possible target for colorectal cancer prevention

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2009
Kathleen E. Kearney
Abstract Aberrant crypt foci (ACF), the earliest identified monoclonal lesions in the colon, provide insights into changes that promote and/or accompany the transformation of normal colonic epithelial cells to colorectal cancer. Fatty acid synthase (FAS), the primary enzyme involved in de novo lipogenesis from carbohydrates, is expressed at low levels in most normal human tissues but is elevated in several human neoplasms including colorectal adenomas and carcinomas. To determine if this pathway is altered even earlier in colorectal tumorigenesis, 35 human ACF from 21 patients were evaluated for the immunohistochemical expression of FAS. Sections of colon cancer served as positive controls, and normal colonic mucosa distant from cancer or ACF served as negative controls. FAS expression was increased in 30 (86%) ACF compared with that in adjacent normal colonic mucosa. The expression of FAS in ACF was not related to the degree of dysplasia or to the number of crypts in the ACF. The over expression of FAS in a high proportion of ACF suggests that this enzyme plays an important role very early in colorectal tumorigenesis and may be a target for chemoprevention. © 2009 UICC [source]

Beta2-microglobulin mutations in microsatellite unstable colorectal tumors

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2007
Matthias Kloor
Abstract Defects of DNA mismatch repair (MMR) cause the high level microsatellite instability (MSI-H) phenotype. MSI-H cancers may develop either sporadically or in the context of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome that is caused by germline mutations of MMR genes. In colorectal cancer (CRC), MSI-H is characterized by a dense lymphocytic infiltration, reflecting a high immunogenicity of these cancers. As a consequence of immunoselection, MSI-H CRCs frequently display a loss of human leukocyte antigen (HLA) class I antigen presentation caused by mutations of the ,2 -microglobulin (,2m) gene. To examine the implications of ,2m mutations during MSI-H colorectal tumor development, we analyzed the prevalence of ,2m mutations in MSI-H colorectal adenomas (n = 38) and carcinomas (n = 104) of different stages. Mutations were observed in 6/38 (15.8%) MSI-H adenomas and 29/104 (27.9%) MSI-H CRCs. A higher frequency of ,2m mutations was observed in MSI-H CRC patients with germline mutations of MMR genes MLH1 or MSH2 (36.4%) compared with patients without germline mutations (15.4%). The high frequency of ,2m mutations in HNPCC-associated MSI-H CRCs is in line with the hypothesis that immunoselection may be particularly pronounced in HNPCC patients with inherited predisposition to develop MSI-H cancers. ,2m mutations were positively related to stage in tumors without distant metastases (UICC I-III), suggesting that loss of ,2m expression may promote local progression of colorectal MSI-H tumors. However, no ,2m mutations were observed in metastasized CRCs (UICC stage IV, p = 0.04). These results suggest that functional ,2m may be necessary for distant metastasis formation in CRC patients. © 2007 Wiley-Liss, Inc. [source]

The Vienna classification applied to colorectal adenomas

Risk of colorectal adenomas in patients with coeliac disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010
B. Lebwohl
Aliment Pharmacol Ther 2010; 32: 1037,1043 Summary Background, Coeliac disease is associated with an increased risk of lymphoma and small bowel malignancy, but most studies have found no increased risk of colorectal cancer. Aim, To compare the prevalence of colorectal adenomas in coeliac disease patients with that in non-coeliac disease controls. Methods, We identified all coeliac disease patients who underwent colonoscopy at our institution during a 44-month period. We matched each patient with non-coeliac disease controls by age, gender and endoscopist. We compared the adenoma prevalence between these groups, and used multivariate analysis to assess the independent association of coeliac disease with adenomas. Results, We identified 180 patients with coeliac disease and 346 controls. At least one adenoma was present in 13% of coeliac disease patients and 17% of controls (P = 0.20). On multivariate analysis, age (OR per year 1.04, 95% CI 1.02,1.07) and male gender (OR 2.33, 95% CI 1.36,3.98) were associated with adenomas, while the relationship between coeliac disease and adenomas remained null (OR 0.75, 95% CI 0.41,1.34). Conclusions, Coeliac disease is not associated with an increased risk of colorectal neoplasia. The lack of increased risk of colorectal cancer observed in population studies is related to a true average risk of colorectal neoplasia, rather than artifactually reflecting increased colonoscopy and associated polypectomies in the coeliac population. [source]

Meta-analysis: folic acid in the chemoprevention of colorectal adenomas and colorectal cancer

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010
C. CARROLL
Aliment Pharmacol Ther,31, 708,718 Summary Background, Folic acid has been identified as a possible agent for the chemoprevention of colorectal cancer. Aim, To assess the effectiveness of folic acid in reducing the recurrence of adenomas (precursors of colorectal cancer) among populations with a history of adenomas and the incidence of colorectal cancer within average-risk populations. Methods, Systematic review of randomized controlled trials comparing folic acid alone, or with other agents, vs. placebo. Eight databases were searched for relevant trials. Meta-analysis was performed. Results, The literature search retrieved 3785 citations. Six studies met the inclusion criteria. Meta-analysis of three studies in individuals with a history of adenomas showed no statistically significant difference in the relative risk of adenoma recurrence (RR 0.93, P = 0.27). A sensitivity analysis of the two higher quality trials changed the direction of effect (RR 1.16, P = 0.11). Meta-analysis of three trials in general populations demonstrated no statistically significant effect on the relative risk of colorectal cancer (RR 1.13, P = 0.54). In all three analyses, outcome event rates were higher in individuals receiving folic acid. Conclusion, There is no evidence that folic acid is effective in the chemoprevention of colorectal adenomas or colorectal cancer for any population. [source]

Identification of colorectal adenomas by a quantitative immunochemical faecal occult blood screening test depends on adenoma characteristics, development threshold used and number of tests performed

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2009
P. ROZEN
Summary Background Faecal occult blood tests (FOBT) are faulted by low sensitivity for advanced adenomatous polyps (AAP). Quantified, immunochemical, haemoglobin (Hb)-specific immunochemical FOBT (I-FOBT) measurements are now used for colorectal screening. Aims To correlate adenoma characteristics to amount of faecal Hb lost and to evaluate sensitivity and specificity for AAP by faecal Hb development threshold used and number of I-FOBTs collected. Methods Three daily I-FOBTs were collected and analysed in 1221 patients scheduled for colonoscopy. Faecal Hb was analysed as ngHb/mL of buffer and the highest result related to colonoscopy findings. Results In 1204 patients without cancer, colonoscopy identified adenomas in 294, 99 with AAPs. Adenoma patients had elevated faecal Hb increasing with advanced histology, size, pedunculated shape and multiplicity (P < 0.001 for all). At 50 ngHb/mL threshold, sensitivity and specificity for AAPs were 54.5% (95%CI 44.7, 64.7) and 88.1% (95%CI 86.2, 90.1) for three tests. At higher thresholds, sensitivity decreased, but was significantly higher with more samples collected. Conversely, specificity increased at higher thresholds, but decreased with more samples. Conclusions Faecal Hb loss from adenomas is significantly associated with size, number and advanced features. Sensitivity and specificity for AAPs are determined by test threshold chosen and number of samples collected; these determine the number of colonoscopies needed for positive tests. [source]

Time trends in first-diagnosis rates of colorectal adenomas: a 24-year population-based study

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2008
V. COTTET
Summary Background, Little is known about the descriptive epidemiology of colorectal adenomas diagnosed in the population. Aim, To describe time trends in the rate of first diagnosis of colorectal adenomas and estimate the proportion of adenoma-bearing individuals detected over a 24-year period. Methods, A total of 11 027 patients were first-diagnosed with colorectal adenomas among Côte-d'Or residents (France) between 1976 and 1999. Annual percentage changes were estimated using a Poisson regression model. The proportion of diagnosed adenoma-bearing individuals was estimated using the prevalence of adenomas in an autopsy study performed in the area. Results, Standardized diagnosis rates were 89.6/100 000 men and 50.3/100 000 women. During the period 1976,1993, diagnosis rates significantly increased with annual percentage changes in men and women of respectively +17.1% and +22.3% for proximal adenomas, +7.5% and +9.1% for distal adenomas and +7.2% and +8.0% for advanced adenomas. Changes were less marked during the period 1994,1999. The estimated proportion of adenoma-bearing individuals diagnosed during the 24-year period was 20.0% in men and 16.0% in women. Conclusion, Despite a marked increase in the rate of first adenoma diagnosis, the proportion of diagnosed adenoma-bearing individuals seems too low to induce a significant decrease in colorectal cancer incidence. [source]

Low compliance with colonoscopic screening in first-degree relatives of patients with large adenomas

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2006
V. COTTET
Summary Background Little is known about compliance with colonoscopy as a screening method in first-degree relatives of patients with large adenomas. Aims To evaluate the compliance with screening colonoscopy among this population, and its determinants. Methods Data were obtained from the family part of the GEADE study, a study on genetic factors of colorectal adenomas. Index cases were 306 patients with adenomas , 10 mm. All living first-degree relatives aged 40,75 who could be contacted by the index case were asked to undergo a colonoscopy, unless they had had one in the previous 5 years. Results Among 674 eligible relatives, 56 had had a colonoscopy within the preceding 5 years and 114 underwent a screening colonoscopy resulting in a compliance with screening colonoscopy of 18%. This was not related to most characteristics of index cases. Compliance was significantly lower when the index case lived in the Greater Paris area than when he/she lived in other areas (12% vs. 21%). It was higher in siblings (18%) and offspring (23%) than in parents (9%) and in relatives under 55 years old (22%) than in relatives aged 55 and over (15%). Conclusions Compliance with colonoscopy was low in first-degree relatives of patients with large adenomas. The reasons for this should be determined and appropriate strategies developed to increase compliance. [source]

Oral and maxillofacial manifestations of familial adenomatous polyposis

ORAL DISEASES, Issue 4 2007
MA Wijn
Patients with familial adenomatous polyposis (FAP) develop multiple premalignant colorectal adenomas. Untreated, one or more of these polyps will progress to colorectal carcinoma in middle-aged adults. Extra-intestinal manifestations of FAP are frequently observed and this combination has been called Gardner's syndrome. Oral and maxillofacial symptoms of FAP include an increased risk of jaw osteomas, odontomas and supernumerary or unerupted teeth. Early diagnosis of FAP is crucial and may be life saving. As oral signs usually precede gastrointestinal symptoms, the dentist may play an important role in the diagnosis of FAP. [source]

Basement membrane laminin-5 is deposited in colorectal adenomas and carcinomas and serves as a ligand for ,3,1 integrin

APMIS, Issue 3 2000
Jouni Lohi
Interplay between laminin-5 (Ln-5) and its integrin (Int) receptors ,2,1, ,3,1 and ,6,4 has been implicated in the progression and invasion of carcinomas. In this study we found abundant immuno-reactivity for chains of Ln-5 (,3-,3-,2) and Ln-10 (,5-,1), as well as for type VII collagen, in basement membranes (BM) of colorectal adenomas. In carcinomas of all differentiation grades, Lns were seen in tumor BMs, whereas type VII collagen was almost absent. Ln-5 appeared to accumulate along the invading edges of carcinomas, while Ln-10 was mostly absent. Immunoreactivity for Ln ,1 chain, a component of Lns-1 and -3, was not seen in adenomas or carcinomas. Immunoreactivity for ,2, ,6, ,1 and ,4 Ints was found in all tumors and that for ,3 Int in all adenomas and most of the carcinomas, often in colocalization with Ln-5. Immunoblotting of carcinoma tissues showed that the ,2 chain of Ln-5 was present as typical Mr 105000 and 155000 isoforms. Immunoprecipitation experiments showed production of Ln-5 by cultured colon carcinoma cells. In quantitative cell adhesion experiments, function-blocking MAbs to ,3 and ,1 Int subunits, but not those to Int ,2 or ,6 subunits, significantly inhibited the adhesion of cells to Ln-5. Our results suggest that BM composition in colorectal adenomas reflects the properties of surface epithelial BM of colorectal mucosa. In invading carcinomas, trimeric Ln-5, produced by carcinoma cells, is a major BM component and the cells use the ,3,1 Int complex for adhesion to Ln-5. [source]

High-risk colorectal adenomas and serum insulin-like growth factors

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2001
A. G. Renehan
Background: This study investigated the hypothesis that circulating levels of insulin-like growth factor (IGF) I and its main binding protein (IGFBP-3) predict for the presence of colorectal adenomas, surrogate markers of colorectal cancer risk. Methods: Within the Flexi-Scope Trial (healthy volunteers aged 55,64 years), at one study centre, IGF-I and IGFBP-3 levels in serum samples collected prospectively from 442 attendants were measured. Of these, 100 individuals underwent a complete screening colonoscopy. There were 47 normal examinations, while in 11 examinations low-risk adenomas and in 42 examinations high-risk adenomas were identified. Estimates of relative risk (RR) for the adenomatous stages were calculated by means of unconditional logistic regression, adjusting for known risk factors. Results: Mean serum IGF-I and IGFBP-3 levels were similar in individuals with a normal colonoscopy finding and in those with low-risk adenomas. By contrast, the mean(s.d.) serum IGF-I level was increased (190(53) versus 169(54) µg/l; P = 0·06) and the serum IGFBP-3 concentration was significantly decreased (3·22(0·60) versus 3·47(0·62) mg/l; P = 0·05) in individuals with high-risk adenomas compared with levels in those with normal colonoscopy and low-risk adenomas combined. Levels were unaffected by removal of the adenomas. With high-risk adenoma as the dependent factor, regression models demonstrated a significant positive association with IGF-I after controlling for IGFBP-3 (RR per one standard deviation (1s.d.) change 4·39 (95 per cent confidence interval (c.i.) 1·31,14·7); P = 0·02) and, independently, an inverse association with IGFBP-3 after adjustment for IGF-I (RR per 1s.d. change 0·41 (95 per cent c.i. 0·20,0·82); P = 0·01). Conclusion: These findings suggest that circulating IGF-I and IGFBP-3 levels are related to future colorectal cancer risk and, specifically, may predict adenoma progression. © 2001 British Journal of Surgery Society Ltd [source]

Calcium, dietary, and lifestyle factors in the prevention of colorectal adenomas

CANCER, Issue 3 2007
Eric A. Miller PhD
Abstract BACKGROUND. Many studies have suggested a role for calcium in reducing the risk of colorectal adenomas and cancer but its effectiveness may be dependent on interactions with other dietary and/or lifestyle factors. We examined the association between calcium and prevalence of adenomas and assessed whether the association was stronger in biologically plausible subgroups. METHODS. Cross-sectional data from 222 cases and 479 adenoma-free controls who underwent colonoscopies and completed food frequency and lifestyle questionnaires were used in the analyses. Multivariable logistic regression was used to estimate the association between calcium and prevalence of adenomas. Stratified analyses and the likelihood ratio test were used to examine effect modification by various demographic, lifestyle, and behavioral factors. RESULTS. Overall, little association was observed comparing total calcium intake of ,900 mg/day to <500 mg/day (adjusted odds ratio [OR] = 0.85, 95% confidence interval [CI]: 0.53,1.37). However, stronger associations were observed in patients with lower fat intake and in those who regularly (,15 times/month) took nonsteroidal antiinflammatory drugs (NSAIDs). Specifically, total calcium intake of ,900 mg/day was associated with a lower prevalence of adenomas among patients with lower fat intake (OR = 0.47, 95% CI: 0.25,0.91) but not among those with higher fat intake (OR = 1.20, 95% CI: 0.61,2.35; P -value for interaction = .01). For NSAIDs, the associations were OR = 0.37 (95% CI: 0.16,0.86) for regular NSAID users and OR = 1.27 (95% CI: 0.73,2.22) with infrequent or nonuse of NSAIDs, respectively (P = .06). CONCLUSIONS. The data suggest that a lower-fat diet and regular NSAID use may enhance calcium's effectiveness as a colorectal cancer preventive agent. Cancer 2007 © 2007 American Cancer Society. [source]

DNA repair dysfunction in gastrointestinal tract cancers

CANCER SCIENCE, Issue 3 2008
Yoshihiko Maehara
The DNA repair system surveys the genome, which is always suffering from exposure to both exogenous as well as endogenous mutagens, to maintain the genetic information. The fact that the basis of this DNA repair system is highly conserved, from prokaryote to mammalian cells, suggests the importance of precise genome maintenance mechanisms for organisms. In the past 15 years, considerable progress has been made in understanding how repair processes interact and how disruptions of these mechanisms lead to the accumulation of mutations and carcinogenesis. In 1993, two groups reported that DNA mismatch repair could be associated with hereditary non-polyposis colorectal cancer, indicating a connection between faulty DNA repair function and cancer. More recently, an inherited disorder of DNA glycosylase, which removes mutagenic oxidized base from DNA, has been reported in individuals with a predisposition to multiple colorectal adenomas and carcinomas. This is the first report that directly indicates the role of the repair of oxidative DNA in human inherited cancer. Studies from gene knockout mice have elucidated the principal role of these repair systems in the process of carcinogenesis. Moreover, clinical samples derived from cancer patients have shown the direct involvement. This review focuses on the function of DNA mismatch repair and oxidative DNA/nucleotide repair among various DNA repair systems in cells, both of which are essentially involved in the carcinogenesis of gastrointestinal tract cancer. (Cancer Sci 2008; 99: 451,458) [source]

Genetic polymorphisms of cyclooxygenase-2 and colorectal adenoma risk: The Self Defense Forces Health Study

Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population

CANCER SCIENCE, Issue 2 2008
Hong Tao
The MUTYH gene encodes a DNA glycosylase that can initiate the base excision repair pathway and prevent G:C > T:A transversion by excising adenine mispaired with 8-hydroxyguanine. Biallelic germline mutations of MUTYH have been shown to predict familial and sporadic multiple colorectal adenomas and carcinomas, however, whether there is an association between single nucleotide polymorphisms (SNPs) of MUTYH and sporadic colorectal cancer (CRC) risk has remained unclear. In this study we investigated four MUTYH SNPs, IVS1+11C > T, IVS6+35G > A, IVS10,2A > G, and 972G > C (Gln324His), for an association with increased CRC risk in a population-based series of 685 CRC patients and 778 control subjects from Kyushu, Japan. A statistically significant association was demonstrated between IVS1+11T and increased CRC risk (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.012,2.030; P = 0.042) and one of the five haplotypes based on the four SNPs, the IVS1+11T , IVS6+35G , IVS10,2A , 972C (TGAC) haplotype containing IVS1+11T, was demonstrated to be associated with increased CRC risk (OR, 1.43; 95% CI, 1.005,2.029; P = 0.046). Subsite-specific analysis showed that the TGAC haplotype was statistically significantly (P = 0.013) associated with an increased risk of distal colon, but not proximal colon or rectal cancer. Furthermore, IVS1+11C > T was found to be in complete linkage disequilibrium with ,280G > A and 1389G > C (Thr463Thr). The results indicated that Japanese individuals with , 280A/IVS1+11T/1389C genotypes or the TGAC haplotype are susceptible to CRC. (Cancer Sci 2008; 99: 355,360) [source]