Cumulative Risk Of Colorectal Cancer Research Articles

Importance of Family History of Colorectal Carcinoma In Situ Versus Invasive Colorectal Cancer: A Nationwide Cohort Study.

The aim of this study was to explore the risk of invasive colorectal cancer (CRC) in relatives of patients with colorectal carcinoma in situ (CCIS), which is lacking in the literature. We collected data from Swedish family-cancer datasets and calculated standardized incidence ratio (SIR) and cumulative risk of CRC in family histories of CCIS in first- and second-degree relatives. Family history was defined as a dynamic (time-dependent) variable allowing for changes during the follow-up period from 1958 to 2015. Of 12,829,251 individuals with available genealogical data, 173,796 were diagnosed with CRC and 40,558 with CCIS. The lifetime (0-79 years) cumulative risk of CRC in first-degree relatives of patients with CCIS was 6.5%, which represents a 1.6-fold (95% CI, 1.5-1.7; n=752) increased risk. A similarly increased lifetime cumulative risk (6.7%) was found among first-degree relatives of patients with CRC (SIR, 1.6; 95% CI, 1.6-1.7; n=6,965). An increased risk of CRC was also found in half-siblings of patients with CCIS (SIR, 1.9; 95% CI, 1.1-3.0; n=18) and also in half-siblings of patients with CRC (SIR, 1.7; 95% CI, 1.3-2.1; n=78). Moreover, the increased risk of CRC was higher for younger age at diagnosis of CCIS in the affected first-degree relative and for younger age at diagnosis of CRC in the index person. Results of this study show that first-degree relatives and half-siblings of patients with CCIS have an increased risk of CRC, which is comparable in magnitude to the risk of those with a family history of invasive CRC. These findings extend available evidence on familial risk of CRC and may help to refine guidelines and recommendations for CRC screening.

Cumulative risks of colorectal cancer in Han Chinese patients with Lynch syndrome in Taiwan

Patients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%–89.9%) and 76.7% (95% CI = 37.2%–99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%–57.7%) and 49.3% (95% CI = 21.9%–84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.

P290 Long-term disease outcome of ulcerative colitis (UC) in South Ostrobothnia, Finland with a follow-up time of 25 years

Abstract Background Finland has one of the highest prevalence of inflammatory bowel disease (IBD), especially UC. There is scarce data about long-term disease outcome in UC in population-based cohorts. The aim was to evaluate the long-term clinical outcome of patients with UC in the region of South Ostrobothnia, a district in rural central western Finland with a population of about 190 000. Methods All patients treated with diagnosis of UC or IBDU (inflammatory bowel disease Unclassified) during years 1981–2000 were included in this study. Data were collected retrospectively from the patient registry of the Central Hospital of South Ostrobothnia until 1 August 2019. Results There were 589 patients with a median follow-up time of 25 years. Median age at the diagnosis was 34 years. 59% of patients were male, 93% had UC and 7% IBDU. According to Montreal classification 80% had extensive disease, 15% left-sided disease and 5% proctitis. Medical treatment used at any point during the disease is shown in Table 1. Twenty-two per cent of patients had colectomy. Of operated patients, (pan)proctocolectomy with ileostomy was performed to 50%, IPAA (ileal pouch anal anastomosis) to 40% and IRA (ileorectal anastomosis) to 3%. Median time from the diagnosis to surgery was 11 years; the risk of surgery is shown in Table 2. Twenty-six per cent of the operations were emergency surgeries. The mean age at the time of surgery was 49 years. The indications for colectomy are specified in Table 3. Cumulative risk of colorectal cancer (CRC) and biliary tract cancer was 3.2% and 1.7%, respectively. Twenty-eight per cent of patients died during follow-up, at the mean age of 72 years. The cause of death was recorded for 91/167 and the most common causes were cardiovascular disease and malignancy. Conclusion In this population-based cohort with surveillance of 25 years 22% patients with UC or IBDU were operated. Even after becoming available, biological medication is rarely used for UC patients diagnosed in the prebiologic era.

Familial aggregation of early-onset cancers.

This registry‐linkage study evaluates familial aggregation of cancer among relatives of a population‐based series of early‐onset (≤40 years) cancer patients in Finland. A cohort of 376,762 relatives of early‐onset cancer patients diagnosed between 1970 and 2012 in 40,538 families was identified. Familial aggregation of early‐onset breast, colorectal, brain and other central nervous system (CNS) cancer and melanoma was explored by standardized incidence ratios (SIR), stratified by relatedness. Gender‐, age‐ and period‐specific population cancer incidences were used as reference. Cumulative risks for siblings and offspring of the proband up to age ≤40 years were also estimated. Almost all early‐onset cancers were sporadic (98% or more). Among first‐degree relatives, SIR was largest in colorectal cancer (14, 95% confidence interval 9.72–18), and lowest in melanoma (1.93, 1.05–3.23). Highest relative‐specific SIRs were observed for siblings in families, where also parent had concordant cancer, 90 (43–165) for colorectal cancer and 29 (11–64) for CNS cancer. In spouses, all SIRs were at population level. Cumulative risk of colorectal cancer by age 41 was 0.98% in siblings and 0.10% in population, while in breast cancer the corresponding risks were 2.05% and 0.56%. In conclusion, early‐onset cancers are mainly sporadic. Findings support high familial aggregation in early‐onset colorectal and CNS cancers. Familial aggregation in multiplex families with CNS cancers was mainly attributed to neurofibromatosis and in colorectal cancer to FAP‐ and HNPCC‐syndromes. The pattern of familial aggregation of early‐onset breast cancer could be seen to support very early exposure to environmental factors and/or rare genetic factors.

Familial colorectal cancer risk in half siblings and siblings: nationwide cohort study

ObjectiveTo explore the risk of colorectal cancer in family members of patients with colorectal cancer, with an emphasis on subtypes of second degree relatives, especially half siblings, which were lacking...

Results of a 36-year surveillance program for ulcerative colitis-associated neoplasia in the Japanese population.

Surveillance colonoscopy has been carried out for patients with long-standing ulcerative colitis who have an increased risk for colorectal cancer. The aim of the present study was to determine the incidence of and the risk factors for neoplasia. We evaluated 289 ulcerative colitis patients who underwent surveillance colonoscopy between January1979 and December 2014. Cumulative incidence of neoplasia and its risk factors were investigated. Clinical stage and overall survival were compared between the surveillance and non-surveillance groups. Cumulative risk of dysplasia was 3.3%, 12.1%, 21.8%, and 29.1% at 10, 20, 30 and 40 years after the onset of ulcerative colitis, respectively. Cumulative risk of colorectal cancer was 0.7%, 3.2%, 5.2%, and 5.2% at 10, 20, 30 and 40 years from the onset of ulcerative colitis, respectively. Total colitis was a risk factor for neoplasia (P = 0.015; hazard ratio, 2.96). Our surveillance colonoscopy program revealed the incidence and risk factors of ulcerative colitis-associated neoplasias in the Japanese population. Total colitis is a risk factor for neoplasia.

Long-term follow-up reveals high incidence of colorectal cancer in Indian patients with inflammatory bowel disease.

As the magnitude of sporadic colorectal cancer (CRC) in India is low, magnitude of CRC in ulcerative colitis (UC) is also considered low. As a result, screening for CRC in UC although advocated may not be followed everywhere. We report our data of UC-related CRC from a low-incidence area of sporadic CRC. A total of 1012 patients with left-sided colitis/pancolitis having more than one full-length colonoscopy performed at least a year after the onset of symptoms were included in retrospective analysis of prospectively maintained case records. In addition, 136 patients with duration of disease >10 years underwent surveillance white-light colonoscopy prospectively during the study period. A total of 1012 individuals were finally included (6542 person-years of follow-up, 68.5% males, disease duration: 6.4 ± 6.8 years). Twenty (1.97%) patients developed CRC. Two (10%) patients developed CRC during the first decade, 10/20 (50%) during the second and 8/20 (40%) after the second decade of disease. The cumulative risk of developing CRC was 1.5%, 7.2% and 23.6% in the first, second and third decade, respectively. Of 136 high-risk UC cases, five (3.6%) had CRC on screening colonoscopy. Disease duration and increasing age of onset were associated with higher risk of CRC. Cumulative risk of CRC in Indian UC patients is as high as 23.6% at 30 years. The risk of CRC increases with increasing age of onset and increasing duration of disease. A low risk of sporadic CRC does not confer a low risk of UC-related CRC, and regular screening is warranted.

Risk of colorectal cancer in Asian patients with ulcerative colitis: a systematic review and meta-analysis

The increased risk of colorectal cancer in ulcerative colitis is well known. The risk of sporadic colorectal cancer in Asian populations is considered low and risk estimates of colorectal cancer related to ulcerative colitis from Asia vary. This meta-analysis is an Asian perspective on the risk of colorectal cancer related to ulcerative colitis. We searched PubMed and Embase for terms related to colorectal cancer in ulcerative colitis from inception to July 1, 2016. The search for published articles was done by country for all countries in Asia. We included studies with information on the prevalence and cumulative risk of colorectal cancer at various timepoints. A random-effects meta-analysis was done to calculate the pooled prevalence as well as a cumulative risk at 10 years, 20 years, and 30 years of disease. Our search identified 2575 articles; of which 44 were eligible for inclusion. Our analysis included a total of 31 287 patients with ulcerative colitis with a total of 293 reported colorectal cancers. Using pooled prevalence estimates from various studies, the overall prevalence was 0·85% (95% CI 0·65-1·04). The risks for colorectal cancer were 0·02% (95% CI 0·00-0·04) at 10 years, 4·81% (3·26-6·36) at 20 years, and 13·91% (7·09-20·72) at 30 years. Subgroup analysis by stratifying the studies according to region or period of the study did not reveal any significant differences. We found the risk of colorectal cancer in Asian patients with ulcerative colitis was similar to recent estimates in Europe and North America. Adherence to screening is therefore necessary. Larger population-based, prospective studies are required for better estimates of the risk. Indo-US Science and Technology Forum.

Dysplasia surveillance - a practical guide.

Dysplasia surveillance - a practical guide.

Mutation Spectrum and Risk of Colorectal Cancer in African American Families with Lynch Syndrome

African Americans (AAs) have the highest incidence of and mortality resulting from colorectal cancer (CRC) in the United States. Few data are available on genetic and nongenetic risk factors for CRC among AAs. Little is known about cancer risks and mutations in mismatch repair (MMR) genes in AAs with the most common inherited CRC condition, Lynch syndrome. We aimed to characterize phenotype, mutation spectrum, and risk of CRC in AAs with Lynch syndrome. We performed a retrospective study of AAs with mutations in MMR genes (MLH1, MSH2, MSH6, and PMS2) using databases from 13 US referral centers. We analyzed data on personal and family histories of cancer. Modified segregation analysis conditioned on ascertainment criteria was used to estimate age- and sex-specific CRC cumulative risk, studying members of the mutation-carrying families. We identified 51 AA families with deleterious mutations that disrupt function of the MMR gene product: 31 in MLH1 (61%), 11 in MSH2 (21%), 3 in MSH6 (6%), and 6 in PMS2 (12%); 8 mutations were detected in more than 1 individual, and 11 have not been previously reported. In the 920 members of the 51 families with deleterious mutations, the cumulative risks of CRC at 80 years of age were estimated to be 36.2% (95% confidence interval [CI], 10.5%-83.9%) for men and 29.7% (95% CI, 8.31%-76.1%) for women. CRC risk was significantly higher among individuals with mutations in MLH1or MSH2 (hazard ratio, 13.9; 95% CI, 3.44-56.5). We estimate the cumulative risk for CRC in AAs with MMR gene mutations to be similar to that of individuals of European descent with Lynch syndrome. Two-thirds of mutations were found in MLH1, some of which were found in multiple individuals and some that have not been previously reported. Differences in mutation spectrum are likely to reflect the genetic diversity of this population.

Mechanisms of Immune Signaling in Colitis-Associated Cancer

The inflammatory bowel diseases ulcerative colitis and Crohn’s disease are associated with an increased risk for the development of colorectal cancer. During recent years, several immune signaling pathways have been linked to colitis-associated cancer (CAC), largely owing to the availability of suitable preclinical models. Among these, chronic intestinal inflammation has been shown to support tumor initiation through oxidative stress–induced mutations. A proinflammatory microenvironment that develops, possibly as a result of defective intestinal barrier function and host–microbial interactions, enables tumor promotion. Several molecular pathways such as tumor necrosis factor/nuclear factor-κB or interleukin 6/signal transducer and activator of transcription 3 signaling have been identified as important contributors to CAC development and could be promising therapeutic targets for the prevention and treatment of CAC.

MUTYH Status and Colorectal Cancer Risk: Implication for Surveillance

MUTYH polyposis (MAP) is responsible for approximately 10 and 30 % of classical and attenuated forms of adenomatous colorectal polyposes, respectively. The underlying molecular mechanism is a biallelic germline mutation of the MUTYH gene responsible for the failure of the base excision repair (BER) DNA repair system with subsequent accumulation of somatic transversion mutations. The cumulative risk of colorectal cancer is very high in the absence of adequate care. Lifelong close colonoscopic surveillance with polypectomies is recommended. Surgery (total rather than partial colectomy) is required when polyp burden exceeds the number that could be safely managed by endoscopy and/or in case of colorectal cancer. Upper gastrointestinal endoscopy is also recommended to detect and to treat duodenal lesions. An increased risk of colorectal cancer is reported in relatives of MAP patients carrying a monoallelic MUTYH mutation. According to the opinion of the majority of experts, these individuals are therefore candidates for colonoscopic surveillance as recommended for first-degree relatives of a patient with sporadic colorectal cancer.

Incidence of colorectal adenomas: birth cohort analysis among 4.3 million participants of screening colonoscopy.

Most colorectal cancers develop from adenomas. We aimed to estimate sex- and age-specific incidence rates of colorectal adenomas and to assess their potential implications for colorectal cancer screening strategies. Sex- and age-specific incidence rates of colorectal adenomas were derived by a birth cohort analysis using data from 4,322,085 screening colonoscopies conducted in Germany and recorded in a national database in 2003-2012. In addition, cumulative risks of colorectal cancer among colonoscopically neoplasm-free men and women were estimated by combining adenoma incidence rates with previously derived adenoma-colorectal cancer transition rates. Estimated annual incidence in percentage (95% confidence interval) in age groups 55-59, 60-64, 65-69, 70-74, and 75-79 was 2.4 (2.2-2.6), 2.3 (2.1-2.6), 2.4 (2.1-2.6), 2.2 (1.8-2.5), and 1.8 (1.2-2.3) among men, and 1.4 (1.3-1.5), 1.5 (1.4-1.7), 1.6 (1.4-1.8), 1.6 (1.3-1.8), and 1.2 (0.8-1.6) among women. Estimated 10- and 15-year risks of clinically manifest colorectal cancer were 0.1% and 0.5% or lower, respectively, in all groups assessed. Annual incidence rates of colorectal adenomas are below 2.5% and 2% among men and women, respectively, and show little variation by age. Risk of clinically manifest colorectal cancer is expected to be very small within 10 years and beyond after negative colonoscopy for men and women at all ages. The use of rescreening after a negative screening colonoscopy above 60 years of age may be very limited.

Su1354 Factors Associated With Large Increases in Self-Reported Health Status in Infliximab-Treated IBD Patients

Introduction: Chronic granulomatous disease (CGD) is an immunodeficiency syndrome caused by a defective NADPH oxidase complex. Afflicted patients are unable to produce adequate reactive oxygen metabolites to neutralize microorganisms within macrophages. Approximately 50% of CGD patients develop gastrointestinal (GI) disease that shares features of both Crohn's disease and ulcerative colitis. In patients with pediatric-onset ulcerative colitis, the cumulative risk for colorectal cancer (CRC) is 2% at 10 years (yrs) and 8% at 20 yrs. While the increased risk of CRC among patients with longstanding inflammatory bowel disease (IBD) is well established, the incidence of CRC among CGD patients with longstanding colitis has not been described. Methods: Patients with CGD colitis were identified from a database comprised of 279 CGD patients seen at the NIH from 1972 to 2011. To allow for adequate endoscopic, pathologic, and clinical follow-up, 78 patients with evidence of CGD colitis seen between 1990 and 2010 were identified, and patients with disease duration >10 yrs were used for formal analysis. The clinical and endoscopic reports over the 10 year follow-up period were reviewed, and the colonic biopsies were reexamined when available. Demographic information, duration of disease, endoscopic findings, and treatment and surgical history were extracted from the electronic medical records. The primary endpoint was the evidence of dysplasia or development of CRC. Results: Of the 78 patients, 20 had disease for >10 yrs. Notably, no colonic dysplasia or CRC were seen at the time of the biopsies in any of these patients. Of the 20 patients with disease > 10 yrs, 8 had biopsies available for formal reexamination. On reexamination, no patients were found to have colonic dysplasia or CRC. For all 20 patients, the average age at diagnosis was 10 years, with the median duration of disease of 16.7 yrs. Polyps were noted in 5 of 20 patients, 3 of which were inflammatory, 1 hyperplastic and 1 normal mucosa. No patients were diagnosed with colorectal cancer during follow-up. Conclusions: Despite long-standing inflammation, there was no dysplasia or CRC among 20 patients with CGD after a median of 16.7 years of follow up. In addition, no cases of colonic dysplasia or CRC were found in any patients with CGD colitis. The incidence of CRC among patients with CGD colitis appears to be lower than the incidence among patients with IBD. In fact, there are no reported cases of malignant polyps, dysplasia, or any gastrointestinal cancers in the short term or long term data. Although limited by a retrospective study design, these data suggest that the development of CRC in the setting of chronic inflammation may be influenced by NADPH activity, suggesting superoxide metabolism as a possible target to prevent oncogenesis.

Su1353 Longstanding Chronic Granulomatous Disease Colitis Does Not Increase the Risk of Colorectal Cancer

Introduction: Chronic granulomatous disease (CGD) is an immunodeficiency syndrome caused by a defective NADPH oxidase complex. Afflicted patients are unable to produce adequate reactive oxygen metabolites to neutralize microorganisms within macrophages. Approximately 50% of CGD patients develop gastrointestinal (GI) disease that shares features of both Crohn's disease and ulcerative colitis. In patients with pediatric-onset ulcerative colitis, the cumulative risk for colorectal cancer (CRC) is 2% at 10 years (yrs) and 8% at 20 yrs. While the increased risk of CRC among patients with longstanding inflammatory bowel disease (IBD) is well established, the incidence of CRC among CGD patients with longstanding colitis has not been described. Methods: Patients with CGD colitis were identified from a database comprised of 279 CGD patients seen at the NIH from 1972 to 2011. To allow for adequate endoscopic, pathologic, and clinical follow-up, 78 patients with evidence of CGD colitis seen between 1990 and 2010 were identified, and patients with disease duration >10 yrs were used for formal analysis. The clinical and endoscopic reports over the 10 year follow-up period were reviewed, and the colonic biopsies were reexamined when available. Demographic information, duration of disease, endoscopic findings, and treatment and surgical history were extracted from the electronic medical records. The primary endpoint was the evidence of dysplasia or development of CRC. Results: Of the 78 patients, 20 had disease for >10 yrs. Notably, no colonic dysplasia or CRC were seen at the time of the biopsies in any of these patients. Of the 20 patients with disease > 10 yrs, 8 had biopsies available for formal reexamination. On reexamination, no patients were found to have colonic dysplasia or CRC. For all 20 patients, the average age at diagnosis was 10 years, with the median duration of disease of 16.7 yrs. Polyps were noted in 5 of 20 patients, 3 of which were inflammatory, 1 hyperplastic and 1 normal mucosa. No patients were diagnosed with colorectal cancer during follow-up. Conclusions: Despite long-standing inflammation, there was no dysplasia or CRC among 20 patients with CGD after a median of 16.7 years of follow up. In addition, no cases of colonic dysplasia or CRC were found in any patients with CGD colitis. The incidence of CRC among patients with CGD colitis appears to be lower than the incidence among patients with IBD. In fact, there are no reported cases of malignant polyps, dysplasia, or any gastrointestinal cancers in the short term or long term data. Although limited by a retrospective study design, these data suggest that the development of CRC in the setting of chronic inflammation may be influenced by NADPH activity, suggesting superoxide metabolism as a possible target to prevent oncogenesis.

Cancer Risks forMLH1andMSH2Mutation Carriers

We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation-carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC), and other cancers for carriers were estimated using modified segregation analysis conditioned on ascertainment criteria. Heterogeneity in risks was investigated using a polygenic risk modifier. Average CRC cumulative risks at the age of 70 years (95% confidence intervals) for MLH1 and MSH2 mutation carriers, respectively, were estimated to be 34% (25%-50%) and 47% (36%-60%) for male carriers and 36% (25%-51%) and 37% (27%-50%) for female carriers. Corresponding EC risks were 18% (9.1%-34%) and 30% (18%-45%). A high level of CRC risk heterogeneity was observed (P < 0.001), with cumulative risks at the age of 70 years estimated to follow U-shaped distributions. For example, 17% of male MSH2 mutation carriers have estimated lifetime risks of 0%-10% and 18% have risks of 90%-100%. Therefore, average risks are similar for the two genes but there is so much individual variation about the average that large proportions of carriers have either very low or very high lifetime cancer risks. Our estimates of CRC and EC cumulative risks for MLH1 and MSH2 mutation carriers are the most precise currently available.

Declining Risk of Colorectal Cancer in Inflammatory Bowel Disease

Recently reported risks of colorectal cancer (CRC) in inflammatory bowel disease (IBD) have been lower than those reported before 2000. The aim of this meta-analysis was to update the CRC risk of ulcerative and Crohn's colitis, investigate time trends, and identify high-risk modifiers. The MEDLINE search engine was used to identify all published cohort studies on CRC risk in IBD. Publications were critically appraised for study population, Crohn's disease localization, censoring for colectomy, and patient inclusion methods. The following data were extracted: total and stratified person-years at risk, number of observed CRC, number of expected CRC in background population, time period of inclusion, and geographical location. Pooled standardized incidence ratios and cumulative risks for 10-year disease intervals were calculated. Results were corrected for colectomy and isolated small bowel Crohn's disease. The pooled standardized incidence ratio of CRC in all patients with IBD in population-based studies was 1.7 (95% confidence interval [CI], 1.2-2.2 ). High-risk groups were patients with extensive colitis and an IBD diagnosis before age 30 with standardized incidence ratios of 6.4 (95% confidence interval, 2.4-17.5) and 7.2 (95% confidence interval, 2.9-17.8), respectively. Cumulative risks of CRC were 1%, 2%, and 5% after 10, 20, and >20 years of disease duration, respectively. The risk of CRC is increased in patients with IBD but not as high as previously reported and not in all patients. This decline could be the result of aged cohorts. The risk of CRC is significantly higher in patients with longer disease duration, extensive disease, and IBD diagnosis at young age.

Important changes in the pattern of colorectal cancer in patients with inflammatory bowel disease

1Department of Epidemiology Research, National Health Surveillance & Research, Orestads Boulevard 5, DK-2300 Copenhagen S, Denmark *Author for correspondence: Tel.: +45 32 68 37 22; tjs@ssi.dk It is generally accepted that both ulcerative colitis (UC) and colonic Crohn’s disease (CD) are associated with an increased risk of colorectal cancer (CRC) [1], but the magnitude of the risk is subject to debate and may have changed over time. Previous reports of severely ill patients referred to tertiary centers suggested a markedly increased risk of CRC in UC, as reflected in a metaanalysis by Eaden and colleagues published in 2001 [2]. The meta-analysis was based on both referral center populations, surgical series, surveillance programs, populationbased cohorts and histology series and reported a cumulative risk of CRC in UC of 2, 8 and 18% after 10, 20 and 30 years, respectively. However, acknowledging that only prognostic data from an unselected patient population (representing the whole spectrum of disease) apply to the average inflammatory bowel disease (IBD) patient, a new meta-analysis was conducted in 2012 [3]. It revealed a 2.4-fold increased risk of CRC in patients with UC, estimated from eight population-based studies covering the time period from 1954 to 2004. However, despite the 2.4-fold increased relative risk, the absolute risk of CRC was only 1.6% overall after 7–24 years (mean: 14 years) of follow-up, with a cumulative probability of CRC of less than 1% at 10 years, 0.4–2% at 15 years and 1.1–5.3% at 20 years follow-up. Notably, these numbers also included sporadic cases of CRC. In addition to a limited absolute risk of CRC in UC, one has to consider the marked changes in the management of IBD over the past 30–40 years. These changes include altered use and type of diagnostics and surgery; increased use of medical therapy, with a shift from the era of sulfasalazine, 5-aminosalicylic acid and corticosteroid treatment to the era of immunomodulatory agents, such as thiopurines; and TNF antagonists. Studies on 5-aminosalicylic acid use and risk of CRC have failed to show a chemopreventive effect [4], whereas thiopurines have recently been suggested to reduce the risk of CRC among patients with IBD [5]. Most likely, “...the absolute risk of colorectal cancer in inflammatory bowel disease is limited and a marked decrease in both risk of colorectal cancer and mortality from colorectal cancer has been observed among patients with ulcerative colitis...” EDITORIAL

Inflammatory Bowel Disease-Associated With Colorectal Cancers in Korea: A Single-Center Experience

Although a colorectal cancer (CRC) is a well-known complication of inflammatory bowel disease (IBD), the epidemiology and characteristics of CRC associated with IBD in Asians are still unclear. We retrospectively reviewed the medical records of IBD patients who were registered at the Asan Medical Center from July 1989 to August 2012. Patients who were diagnosed with CRC at the time of or after diagnosis of IBD were identified. A total of 3575 patients with definite IBD (1877 with ulcerative colitis [UC] and 1698 with Crohn's disease [CD]), were enrolled and 25 patients diagnosed with IBD-associated colorectal adenocarcinoma (15 with UC and 10 with CD) were identified. There were 14 females (56%) and the median age at diagnosis of CRC was 43.1 years (interquartile range [IQR], 32.0-52.1 years). Two UC patients had combined primary sclerosing cholangitis. The median interval from IBD diagnosis to cancer diagnosis was 11 years (IQR, 5.1-16.8 years). Five patients (20%) were diagnosed with cancer at the time of IBD diagnosis. Three patients (12%) had synchronous lesions. The histologies of CRCs were as follows; moderately differentiated adenocarcinoma in 11 (44%), mucinous adenocarcinoma in 6 (24%), poorly differentiated adenocarcinoma in 4 (16%), well differentiated adenocarcinoma in 3 (12%), and signet ring cell carcinoma in 1 (4%). The stage distribution of cancer was as follows; I in 3 (12%), II in 8 (32%), III in 5 (20%) and IV in 9 (36%). The cumulative risk of CRC in IBD, UC and CD patients were 0.6%, 0.7% and 0.5%, respectively after 10 years and 5.8%, 5.1% and 7.2% respectively after 20 years. The IBD-associated CRC tends to show an advanced stage at diagnosis. The risk of CRC in Korean IBD patients appears to be comparable to that of Western IBD patients.

Evidence for accelerated colorectal adenoma–carcinoma progression in MUTYH-associated polyposis?

Background and aimMUTYH-associated polyposis (MAP) is an autosomal recessive inherited disorder characterised by the development of polyposis in the upper and lower gastrointestinal tract and a high risk of colorectal...