Population-based screening for colorectal cancer using an immunochemical faecal occult blood test: A comparison of two invitation strategies

Background: To date, there is no screening programme for colorectal cancer (CRC) in Flanders, Belgium. However, The European Code Against Cancer (2003) recommends a population-based approach for CRC screening. This study aimed to obtain information about potential participation rates for a population-based screening programme for CRC in Flanders, and to compare two invitation strategies. Methods: In 2009, a trial programme for CRC screening was set up in three Flemish areas for all average-risk people aged 50-74 years, using an immunochemical faecal occult blood test (iFOBT) with a cut-off value set at 75ng/ml of haemoglobin. The faecal sampling set was sent at random by post (mail group) or provided by the general practitioner (GP group). Results: In total, 19,542 people were invited to participate. Of these, 8229 provided a faecal sample, resulting in an overall participation rate of 42.1%. Participation by mail and through the GP was 52.3% (95% CI, 51.3-53.2) and 27.7% (95% CI, 26.7-28.6), respectively. The difference of 24.6% was statistically significant (95% CI, 23.3-25.9, p<0.001). Before the reminder letter was sent and the other invitation strategy was offered, the overall participation rate was 26.5% (n=5176); 36.4% (95% CI, 35.5-37.4) for the mail group and 16.6% (95% CI, 15.8-17.3) for the GP group. The odds of participating in CRC screening was almost three times higher for people invited by mail as opposed to people invited through a GP (OR=2.96, 95% CI, 2.78-3.14, p<0.001). Women were more likely to participate in CRC screening than men (OR=1.22, 95% CI, 1.15-1.30, p<0.001). In addition, we found that inhabitants from residential (OR=1.98, 95% CI, 1.85-2.11) and rural (OR=2.90, 95% CI, 2.66-3.16) areas were more likely to participate than those in urban areas. Of the 8229 people who submitted a faecal sample, 435 (5.3%) had a positive iFOBT, and of those, CRC was diagnosed in 18 (5.7%) individuals. Compliance for follow-up colonoscopy was 72.9%, and did not differ between the mail (72.4%, 95% CI, 67.5-77.3) and GP groups (74.3, 95% CI, 66.2-82.5). Conclusion: Inviting people for CRC screening by means of a direct-mail invitation, and including a faecal sampling set (iFOBT), results in much higher participation rates than inviting people through the GP.     

Regret on Choice of Colorectal Cancer Screening Modality Was Associated with Poorer Screening Compliance: A 4-Year Prospective Cohort Study

Purpose

Very few studies examined the issue of regret on choosing colorectal cancer (CRC) screening tests. We evaluated the determinants of regret and tested the hypothesis that regret over screening choices was associated with poorer screening compliance.

Methods

A bowel cancer screening centre invited all Hong Kong citizens aged 50-70 years who were asymptomatic of CRC to participate in free-of-charge screening programmes. Upon attendance they attended health seminars on CRC and its screening, and were offered an option to choose yearly faecal immunochemical test (FIT) for up to four years vs. one direct colonoscopy. They were not allowed to switch the screening option after decision. A self-administered, four-item validated survey was used to assess whether they regretted over their choice (> 2 = regretful from a scale of 0 [no regret]-5 [extreme regret]). A binary logistic regression model evaluated if initial regret over their choice was associated with poorer programme compliance.

Results

From 4,341 screening participants who have chosen FIT or colonoscopy, 120 (2.8%) regretted over their decision and 1,029 (23.7%) were non-compliant with the screening programme. Younger subjects and people who felt pressure when making their decision were associated with regret. People who regretted their decision were 2.189 (95% C.I. 1.361-3.521, p = 0.001) times more likely to be non-compliant with the programme.

Conclusions

This study is the first to show that regret over the initial CRC screening choice was associated with later non-compliance. Screening participants who expressed regret over their choice should receive additional reminders to improve their programmatic compliance.     

Factors associated with practice of colorectal cancer screening among primary care physicians in a Chinese population: A cross-sectional study

Objectives: Primary care physicians (PCPs) are influential in colorectal cancer (CRC) screening uptake in the community. This study aims to evaluate the factors associated with PCPs’ practice of CRC screening among asymptomatic patients in a Chinese population. Methods: A validated postal questionnaire was sent to all practicing PCPs who were members of a community-based network in Hong Kong. Three separate rounds of reminder letters were sent to non-respondents. Binary logistic regression analysis was used with ever-referral for CRC screening in the past 12 months as the outcome variable. Predictor variables include physicians’ gender, clinical experience, types of practice, and attitudes towards CRC screening. Results: Of 428 eligible physicians, 263 (61.4%) responded. A total of 187 physicians (71.1%) had referred patients for CRC screening in the past 1 year. Among all asymptomatic patients aged 50 years or older, physicians reported referring only 3.0% (1.0–10.0%) [median (interquartile range)] of patients. Colonoscopy (57.0%) and fecal occult blood testing (FOBT) (46.4%) were the most commonly recommended tests for these asymptomatic patients. Family history of CRC (58.6%) and patients’ concern about CRC (50.2%) were major reasons for referral. PCPs in private practice (adjusted odds ratio [aOR] 2.60, 95% C.I. 1.21–5.59) and those with positive attitude towards CRC screening (aOR 2.27, 95% C.I. 1.15–4.48) were more likely to recommend CRC screening. Conclusions: PCPs’ attitude towards CRC screening is a significant determinant of its practice. Future studies should identify and strengthen the influencers of PCPs’ attitude to enhance CRC screening rates.     

Factors Associated with Adenoma Detection Rate and Diagnosis of Polyps and Colorectal Cancer during Colonoscopy in France: Results of a Prospective,Nationwide Survey

Introduction

Colonoscopy can prevent deaths due to colorectal cancer (CRC) through early diagnosis or resection of colonic adenomas. We conducted a prospective, nationwide study on colonoscopy practice in France.

Methods

An online questionnaire was administered to 2,600 French gastroenterologists. Data from all consecutive colonoscopies performed during one week were collected. A statistical extrapolation of the results to a whole year was performed, and factors potentially associated with the adenoma detection rate (ADR) or the diagnosis of polyps or cancer were assessed.

Results

A total of 342 gastroenterologists, representative of the overall population of French gastroenterologists, provided data on 3,266 colonoscopies, corresponding to 1,200,529 (95% CI: 1,125,936-1,275,122) procedures for the year 2011. The indication for colonoscopy was CRC screening and digestive symptoms in 49.6% and 38.9% of cases, respectively. Polypectomy was performed in 35.5% of cases. The ADR and prevalence of CRC were 17.7% and 2.9%, respectively. The main factors associated with a high ADR were male gender (p=0.0001), age over 50 (p=0.0001), personal or family history of CRC or colorectal polyps (p<0.0001 and p<0.0001, respectively), and positive fecal occult blood test (p=0.0005). The prevalence of CRC was three times higher in patients with their first colonoscopy (4.2% vs. 1.4%; p<0.0001).

Conclusions

For the first time in France, we report nationwide prospective data on colonoscopy practice, including histological results. We found an average ADR of 17.7%, and observed reduced CRC incidence in patients with previous colonoscopy.     

Randomised trial of compliance with screening for colorectal cancer.

A randomised trial of compliance with screening for colorectal cancer by means of the haemoccult test was conducted in Farnborough and Basingstoke districts. In each of the 14 participating practices (41 general practitioners) 25 852 men and women aged between 40 and 70 years were randomly allocated by household to one of six groups. The group determined the method of invitation to screening: a letter and the test were sent to the patient, or a letter with an appointment to attend the surgery was sent, or during a routine consultation the general practitioner invited patients to participate, and some patients received an educational booklet about bowel disorders and screening. Of the 17 824 people who were offered screening, 7545 (42%) complied. Compliance was significantly affected by the method of invitation, but not by whether an educational booklet was received, and was highest (57%) in the group that was offered the haemoccult test during a routine consultation (the "opportunistic" approach). In this group the compliance rate achieved by individual general practitioners ranged from 26% to 82%. Compliance was significantly higher in Farnborough, in the older (55-70) age group, in women, and in households in which two or more people were offered screening. The higher compliance in Farnborough may be explained by the higher proportion of older people and by the higher proportion of people living in households of two or more in the population that was offered screening. The fact that the screening programme in Farnborough was offered to the whole community and that the researcher may have acted as a facilitator were probably also important. One per cent of the patients screened had a positive test, and 24 (38%) of the 63 patients who were positive and were investigated in hospital had neoplastic disease. The yield was 1.2 cancers and 1.2 benign adenomas (1 cm or larger in size) per 1000 people screened. This low yield is likely to be a consequence of the relatively young age group screened.     

Body mass index and screening for colorectal cancer: gender and attitudinal factors

Background: Overweight/obese women and men are at increased risk for colorectal cancer (CRC) incidence and mortality. Research examining body mass index (BMI) and CRC screening has had mixed results. A clearer understanding of the extent to which high-BMI subgroups are screened for CRC is needed to inform planning for CRC screening promotions targeting BMI. Methods: Data were obtained from a random, population-based sample of women and men at average-risk for CRC (aged 50–75 years) during 2004 (n = 1098). Multiple logistic regression analyses were conducted to evaluate whether BMI category was significantly associated with the probability of reporting recent CRC screening and with the probability of agreeing with statements denoting attitudes/perceptions about CRC and screening. Attitudes/perceptions about CRC and screening were evaluated as potential mediators and moderators of the association between BMI category and CRC screening. Results: After controlling for characteristics associated with CRC screening, overweight and obese women were each 40% less likely to have CRC screening than women with normal-BMI (OR = 0.6, 95% CI:0.4–0.9 and OR = 0.6, 95% CI:0.3–0.9). BMI category was unrelated to screening among men. Obese women (but not men) were less aware than normal-BMI women that obesity increased risk for CRC (OR = 0.5, 95% CI:0.3–0.9) and less worried about CRC (OR = 0.5, 95% CI:0.3–0.8). However, findings suggest that attitudes/perceptions about CRC and screening did not mediate or moderate the association between BMI category and CRC screening. Conclusion: Overweight/obese women are at increased risk for CRC because of their greater BMI and their propensity not to screen for CRC. Study findings suggest that potentially modifiable perceptions, e.g., lack of awareness of risk for CRC and less worry about CRC, in this subgroup may not explain the relationship between BMI category and reduced screening.     

Colonoscopic surveillance of first-degree relatives of colorectal cancer patients in a faecal occult blood screening programme

Background: In some Italian areas, colonoscopic surveillance of first-degree relatives (FDRs) of colorectal cancer (CRC) patients is provided as a part of local population-based faecal occult blood test (FOBT) screening programmes. The objective of the present study was to assess the feasibility and early results of this surveillance model. Methods: Data from district screening centres were used to evaluate the process of identification and selection of eligible FDRs (residence in the Emilia-Romagna Region, age 40–75 years, no recent colonoscopy) of screen-detected CRC patients and the detected prevalence of disease. The probability for an FDR to undergo colonoscopy and to be diagnosed with CRC and advanced adenoma was estimated using the Kaplan–Meier method. The sex- and age-standardised ratio of detected prevalence to that expected based on results from a colonoscopy screening study of the Italian general population was estimated. Results: Between 2005 and 2011, 9319 FDRs of 2437 screen-detected CRC patients (3.8 per patient) were identified and contacted. Their likelihood of being eligible for, and accepting, colonoscopy was 0.11 (95% confidence interval: 0.11–0.12). Among the 926 subjects undergoing colonoscopy, the prevalence of previous negative screening FOBT was 63%. Eleven CRCs (1.2%) and 100 advanced adenomas (10.8%) were detected. The standardised ratio of detected prevalence to that expected was 0.91 (95% confidence interval: 0.19–2.66) for CRC and 1.48 (1.04–2.05) for advanced adenoma. Conclusions: The procedure of selection of FDRs was extremely ineffective. Due to previous negative screening tests, the prevalence of disease was less than expected. A population-based FOBT screening programme is a highly unsuitable setting for the provision of surveillance to FDRs of CRC patients.     

Lessons learnt from the implementation of a colorectal cancer screening programme for lynch syndrome in a tertiary public hospital

BackgroundLynch syndrome (LS) is the first cause of inherited colorectal cancer (CRC), being responsible for 2–4% of all diagnoses. Identification of affected individuals is important as they have an increased lifetime risk of multiple CRC and other neoplasms, however, LS is consistently underdiagnosed at the population level. We aimed to evaluate the yield of LS screening in CRC in a single-referral centre and to identify the barriers to its effective implementation.MethodsLS screening programme included individuals with CRC < 70 years, multiple CRC, or endometrial cancer at any age. Mismatch repair (MMR) protein immunohistochemistry (IHC) analysis was performed in routine practice on the surgical specimen and, if MLH1 IHC was altered, MLH1 gene promoter methylation was analysed. Results were collected in the CRC multidisciplinary board database. LS suspected individuals (altered MMR IHC without MLH1 promoter methylation) were referred to the Cancer Genetic Counselling Unit (CGCU). If accepted, a genetic study was performed. Two checkpoints were included: review of the pathology data and verification of patient referral by a genetic counsellor.ResultsBetween 2016 and 2019, 381 individuals were included. MMR IHC analysis was performed in 374/381 (98.2 %) CRC cases and MLH1 promoter methylation in 18/21 (85.7 %). Seventeen of the 20 LS suspected individuals were invited for referral at the CGCU. Two cases were not invited and the remaining patient died of cancer before completion of tumour screening. Fifteen individuals attended and a genetic analysis was performed in 15/20 (75 %) LS suspected individuals. Ten individuals were diagnosed with LS, in concordance with the IHC profile (2.7 % of the total cohort). This led to cascade testing in 58/75 (77.3 %) of the available adult relatives at risk, identifying 26 individuals with LS.ConclusionsEstablishing a standardized institutional LS screening programme with checkpoints in the workflow is key to increasing the yield of LS identification.     

Association between metabolic syndrome and participation in colorectal cancer screening in Japan: A retrospective cohort analysis using LIFE study data

BackgroundPeople with metabolic syndrome have an elevated risk of developing colorectal cancer (CRC), and are recommended to undergo cancer screening. This study examined the association between metabolic syndrome and CRC screening participation in Japan.MethodsThis retrospective cohort study was conducted using insurance claims data, health checkup data, and cancer screening data from a Japanese city. The study population comprised persons aged 40–74 years who had undergone health checkups between fiscal years (FY) 2016 and 2019. The exposure was metabolic syndrome risk (high risk, moderate risk, and no risk) as determined during health checkups. The outcome was CRC screening participation. Logistic regression analyses were performed to examine the associations between metabolic syndrome risk and CRC screening participation.ResultsWe analyzed 20,558 people in the FY2016 cohort, 19,065 people in the FY2017 cohort, 17,496 people in the FY2018 cohort, and 15,647 people in the FY2019 cohort. The odds of CRC screening participation were significantly lower in the moderate-risk group (P < 0.05) in all FYs except FY2019 and the high-risk group (P < 0.001) in all FYs when compared with the no-risk group. When analyzed according to age group, older persons aged 65–74 years generally had significantly lower odds of CRC screening participation than persons aged 40–49 years across all metabolic syndrome risk groups.ConclusionThis is the first study from Japan to show that people with metabolic syndrome, especially older persons aged 65–74 years, are less likely to undergo CRC screening than people without metabolic syndrome. These findings indicate a need to develop and implement age-specific measures to increase cancer screening uptake among persons with metabolic syndrome.     

Perceived Obstacles of Colorectal Cancer Screening and Their Associated Factors among 10,078 Chinese Participants

Purpose

to evaluate the proportion of self-referred screening participants having various psychological barriers and the factors associated with these barriers.

Methods

A territory-wide bowel cancer screening centre sent an invitation via the media to all Hong Kong residents aged 50–70 years who were asymptomatic of CRC to join a free screening programme. Upon attendance they were requested to complete self-administered surveys on their perceived barriers of screening. Binary logistic regression analyses were used to evaluate the factors associated with these barriers.

Results

From 10,078 consecutive screening participants (mean age 57.5 years; female 56.4%) completed the surveys between May 2008 to September 2012. There were high proportions who agreed or strongly agreed with the following barriers: financial difficulty (86.0%), limited service accessibility (58.2%), screening-induced bodily discomfort (55.2%), physical harm (44.4%), embarrassment (40.1%), apprehension (38.8%) and time constraints (13.9%). From regression models, older participants (aged ≥56) were less likely to have these barriers (Adjusted odds ratio [AOR] ranged from 0.738 to 0.952) but they encountered more difficulties to access to screening services (AOR ranged from 1.141 to 1.371). Female subjects were more likely to encounter most of these barriers (AOR ranged from 1.188 to 2.179). Participants who were uncertain of the necessity of CRC screening for people aged ≥50 were more likely to report these barriers (AOR ranged from 1.151 to 1.671).

Conclusion

The proportions of perceptual barriers of CRC screening were high among these participants. Those with these associated factors should receive more thorough explanation of the screening test procedures.     

Circulating Methylated Septin 9 Nucleic Acid in the Plasma of Patients with Gastrointestinal Cancer in the Stomach and Colon

BACKGROUND: Methylated Septin 9 (mSEPT9) in plasma has recently been suggested as a screening marker for colorectal cancer (CRC) with variable sensitivity. We aimed to determine the usefulness of plasma mSEPT9 for screening CRC and gastric cancer (GC) and its diagnostic role in postoperative CRC patients. METHODS: A total of 350 peripheral blood samples from 101 CRC patients, 153 GC patients, and 96 healthy persons were collected. In addition, we obtained 35 follow-up blood samples from 27 CRC patients after curative radical surgery. Plasma mSEPT9, serum carcinoembryonic antigen (CEA), and serum CA19-9 were evaluated with clinicopathologic features. RESULTS: The sensitivity of plasma mSEPT9 was 36.6% for detecting CRC and 17.7% for detecting GC, and the specificity was 90.6%. During follow-up periods, mSEPT9 showed negative conversion in eight of nine CRC patients (88.9%) whose plasma mSEPT9 had been positive before radical surgery. The patients with plasma mSEPT9 had a tendency of presence of distant metastasis and lower disease-free survival in both CRC and GC. In GC patients, plasma mSEPT9 was more frequently observed in intestinal (23.5%) and mixed type (40.0%) than diffuse type (7.3%; P =.009). Combined analysis of mSEPT9, CEA, and CA19-9 increased the sensitivity for diagnosing GC to 32.7% (P = .002). CONCLUSION: Considering the high incidence of plasma mSEPT9 in intestinal or mixed type GCs similar to CRCs, GC should be examined through the plasma mSEPT9 screening test. In addition, plasma mSEPT9 is proposed as a follow-up marker in CRC patients, but further validation is required.     

Are prognostic factors more favorable for breast cancer detected by organized screening than by opportunistic screening or clinical diagnosis? A study in Loire-Atlantique (France)

Purpose: Comparisons of breast cancer characteristics between organized and opportunistic screening have been limited. This study was designed to compare characteristics of cancers detected by either organized or opportunistic screening as well as clinically diagnosed cancers in Loire-Atlantique (a French administrative entity), from 2003 to 2007. Methods: This study is based on data from the population-based Loire-Atlantique Cancer Registry. Stage at diagnosis and prognostic characteristics of carcinomas detected by organized screening were compared, by age-adjusted logistic regressions, to those of cancers detected by opportunistic screening and diagnosed clinically. Analyses were restricted to women aged 50–74 years (the age group targeted by the organized screening program) for the 2003–2007 period. Results: Between 2003 and 2007, 2864 invasive and 400 in situ breast cancer cases were diagnosed in women aged 50–74 years in Loire-Atlantique. Compared to cancers diagnosed clinically, cancers detected by organized screening were more likely to be in situ (13.7% vs. 3.8%), diagnosed at an early stage (74.4% vs. 51.3%), have a low SBR grade (grade 1: 35.4% vs. 18.5%), and be positive for estrogen–progesterone receptors (68.3% vs. 59.0%). The distribution of stage at diagnosis and prognostic characteristics between organized and opportunistic screening were similar. Conclusion: These findings are consistent with the hypothesis that breast cancers are detected early by organized screening. Cancer characteristics were similar between the two screening modes. Estimating the impact of mammography screening on mortality in Loire-Atlantique should be the object of further investigations.     

Urban Chagas disease in children and women in primary care centres in Buenos Aires,Argentina

The primary objective of this study was to estimate the prevalence of this disease in women of childbearing age and children treated at health centres in underserviced areas of the city of Buenos Aires. Demographic and Chagas disease status data were collected. Samples for Chagas disease serology were obtained on filter paper and the reactive results were confirmed with conventional samples. A total of 1,786 subjects were screened and 73 positive screening results were obtained: 17 were from children and 56 were from women. The Trypanosoma cruzi infection risk was greater in those individuals who had relatives with Chagas disease, who remember seeing kissing bugs, who were of Bolivian nationality or were born in the Argentine province of Santiago del Estero. The overall prevalence of Chagas disease was 4.08%. Due to migration, Chagas disease is currently predominantly urban. The observed prevalence requires health programme activities that are aimed at urban children and their mothers. Most children were infected congenitally, which reinforces the need for Chagas disease screening of all pregnant women and their babies in Argentina. The active search for new cases is important because the appropriate treatment in children has a high cure rate.     

Knowledge,perception and practices of colorectal cancer screening in an ethnically diverse population

Background: Colorectal cancer (CRC) screening improves survival and its success depends on the participation of the at-risk population. Few studies have adequately assessed screening knowledge, perception and participation according to birthplace. This study assesses the knowledge and perception of CRC in an ethnically diverse population, and evaluates the association with screening participation and intention. Identification of specific predictors of screening may aid the development of interventions to improve overall CRC screening. Methods: An interview-based survey, conducted on subjects aged 30–70 years, assessed knowledge and perception towards CRC and screening tests. Primary endpoints were screening participation and intent. Statistical methods used were Chi-square, Mann–Whitney U and logistic regression. Results: A total of 543 subjects (43% males, 53% Australian-born (AB), 63% aged 50 years and above) were recruited. Compared with AB, non-Australian-born (NAB) respondents had poorer knowledge, and NAB background predicted for poorer knowledge independent of sex, education, media and familiarity with CRC patient. Compared with AB respondents aged 50 years and above, NAB respondents had lower screening participation (17.4% vs. 31.8%; P = 0.01), lesser intention (75.8% vs. 90.5%; P < 0.001), and had received fewer doctors’ screening recommendations (16.5% vs. 27.1%; P = 0.04). In multivariate analysis, doctors’ recommendation, media and improved perception independently predicted screening participation; knowledge and media exposure predicted intent. Conclusions: The knowledge of CRC and screening is significantly poorer in the immigrant population. Knowledge predicts for greater screening intent. Therefore, implementing language- and culture-specific educational programs involving medical practitioners and media are necessary to improve CRC screening participation rates.     

A gene marker panel covering the Wnt and the Ras-Raf-MEK-MAPK signalling pathways allows to detect gene mutations in 80% of early (UICC I) colon cancer stages in humans

Background: Very recently a gene marker panel that allows the mutational analysis of APC, CTNNB1, B-RAF and K-RAS was conceived. The aim of the present study was to use the 4-gene marker panel covering the Wnt and Ras-Raf-MEK-MAPK signalling pathways to determine the percentage of sporadic colorectal carcinomas (CRC) carrying at least one of the four above-mentioned genes in a mutated form alone and/or in combination with microsatellite instability (MSI) and to compare the sensitivity of the gene marker panel used in this study with that of gene marker panels previously reported in the scientific literature. Methods: CTNNB1 and B-RAF were screened by PCR-single-strand conformation polymorphism analysis and K-RAS gene mutations by restriction fragment length polymorphism analysis. For the mutational analysis of the APC gene mutation cluster region (codons 1243–1567) direct DNA sequencing was performed. The U.S. National Cancer Institute microsatellite panel (BAT25, BAT26, D2S123, D5S346 and D17S250) was used for MSI analysis. Results: It could be shown that about 80% of early stage CRC (UICC stages I and II) and over 90% of CRC in the UICC stage IV carried at least one mutated gene and/or showed MSI. No significant increase in the gene mutation frequencies could be determined when comparing tumours in the UICC stage I with those in UICC stage IV. Conclusions: When compared with previously published gene marker panels the 4-gene marker panel used in the present study shows an excellent performance, allowing to detect genetic alterations in 80–90% of human sporadic CRC samples analyzed.     

Trends and inequities in colorectal cancer screening participation in Ontario,Canada, 2005–2011

Background: Participation in screening tests for colorectal cancer (CRC) is generally low in Ontario, Canada. In addition, inequities in participation exist including lower participation among low-income individuals, males and individuals living in rural areas. In April 2008, Colon Cancer Check (CCC) program, the province-wide CRC screening program, was launched in Ontario. This study describes the trends and inequities in CRC screening participation three years before and three years after the CCC, and assesses the effect of the program on CRC screening participation, overall and among certain population groups. Methods: We used administrative data to identify cohorts of individuals eligible for CRC screening in fiscal years 2005–2011. We calculated the age-standardized percent of Fecal Occult Blood Test (FOBT) participation, large bowel endoscopy participation, and being ‘up-to-date’ with CRC screening tests. Results: From 2005 to 2011, FOBT participation increased from 7.6% to 14.8%, large bowel endoscopy participation from 3.4% to 5.7%, and ‘up-to-date’ with CRC screening from 27.2% to 41.3%. Before the launch of the CCC program, the quarterly increase in FOBT participation was 0.07% (p = 0.19), increased immediately after the launch (1.8%, p < 0.01), followed by a decline (?0.08%, p = 0.08), returning to its pre-program increase rate. We noted a significant decrease in FOBT participation every summer (?0.44%, p < 0.01). The CCC program had minimal effect on large bowel endoscopy participation. Before the launch of the CCC program, the quarterly increase in ‘up-to-date’ with CRC screening was 0.9% (p < 0.01), increased immediately after the launch (2.5%, p = 0.05), followed by a modest decline thereafter (?0.59%, p < 0.02). From 2005 to 2011, recent residents living in low-income neighborhoods were consistently and significantly less likely to have a FOBT and be ‘up-to-date’ with CRC screening than long-term residents living in high-income neighborhoods (2.9–4.5%; 14.7–17.3% respectively). Pre-CCC inequities in CRC participation persisted after the launch of the program. Conclusion: CRC testing was increasing in Ontario from 2005. An immediate increase in CRC testing, FOBT in particular, occurred after the launch of the CCC program, followed by a return to its pre-CCC increase rate thereafter. Future efforts are needed to improve screening participation and address inequities.     

IGFBP3 Methylation Is a Novel Diagnostic and Predictive Biomarker in Colorectal Cancer

Background and Aim

Aberrant hypermethylation of cancer-related genes has emerged as a promising strategy for the development of diagnostic, prognostic and predictive biomarkers in human cancer, including colorectal cancer (CRC). The aim of this study was to perform a systematic and comprehensive analysis of a panel of CRC-specific genes as potential diagnostic, prognostic and predictive biomarkers in a large, population-based CRC cohort.

Patients and Methods

Methylation status of the SEPT9, TWIST1, IGFBP3, GAS7, ALX4 and miR137 genes was studied by quantitative bisulfite pyrosequencing in a population-based cohort of 425 CRC patients.

Results

Methylation levels of all genes analyzed were significantly higher in tumor tissues compared to normal mucosa (p<0.0001); however, cancer-associated hypermethylation was most frequently observed for miR137 (86.7%) and IGFBP3 (83%) in CRC patients. Methylation analysis using the combination of these two genes demonstrated greatest accuracy for the identification of colonic tumors (sensitivity 95.5%; specificity 90.5%). Low levels of IGFBP3 promoter methylation emerged as an independent risk factor for predicting poor disease free survival in stage II and III CRC patients (HR = 0.49, 95% CI: 0.28–0.85, p = 0.01). Our results also suggest that stage II & III CRC patients with high levels of IGFBP3 methylation do not benefit from adjuvant 5FU-based chemotherapy.

Conclusion

By analyzing a large, population-based CRC cohort, we demonstrate the potential clinical significance of miR137 and IGFBP3 hypermethylation as promising diagnostic biomarkers in CRC. Our data also revealed that IGFBP3 hypermethylation may serve as an independent prognostic and predictive biomarker in stage II and III CRC patients.     

Long noncoding RNA Meg3 sponges miR-708 to inhibit intestinal tumorigenesis via SOCS3-repressed cancer stem cells growth

BackgroundColorectal cancer (CRC) remains the most common gastrointestinal cancer and a leading cause of cancer deaths worldwide, with most showing pathologies indicating the malignant transformation of early stage intestinal stem cells. The long non-coding RNA Meg3, which functions as a tumor suppressor, has been reported to be abnormal in multiple tumorigenesis events; however, the underlying mechanism by which Meg3 contributes to the malignant proliferation of colonic stem cells remains unclear.MethodsWe analyzed the expression levels of Meg3, miR-708, and SOCS3 in samples from Apc loss-of-function (Apc^min) mice and patients with CRC, particularly in colonic crypt cells. Apc^min mice and AMO/DSS-induced mice model (in vivo) and organoid culture system (in vitro) were used to explore the effect of the Meg3/miR-708/SOCS3 axis on tumorigenesis in the colon. In vitro, we performed RNApull-down, RNA immunoprecipitation, and luciferase reporter assays using DLD1 and RKO cell lines.FindingsThe Meg3/miR-708/SOCS3 signaling axis plays a critical role in the early stage of CRC development. Our data showed Meg3 levels negatively correlate with miR-708 levels both in clinical samples and in the Apc^min mouse model, which indicated that Meg3 acts as a competitive endogenous RNA (ceRNA) of miR-708. Then, miR-708 served as an oncogene, inducing neoplasia in both Apc^min mice and cultured colonic organoids. Put together, miR-708 appears to promote malignant proliferation of colonic stem cells by targeting SOCS3/STAT3 signaling.InterpretationThese data revealed that Meg3 sponges miR-708 to inhibit CRC development via SOCS3-mediated repression of the malignant proliferation of colonic stem cells. The Meg3/miR-708/SOCS3 signaling axis provides potential targets for the diagnosis and treatment of CRC, particularly early stage CRC.Subject terms: Cancer stem cells, Stem-cell research     

Screening and genetic counselling for relatives of patients with colorectal cancer in a family cancer clinic.

OBJECTIVE--To introduce and monitor a screening programme for first degree relatives of patients with colorectal cancer based on their calculated lifetime risk. DESIGN--Lifetime risks were calculated for first degree relatives of patients with colorectal cancer and used to offer screening based on estimated risk. SETTING--A family cancer clinic was set up as part of the North East Thames Regional Genetic Service for relatives of patients who had developed colorectal cancer before the age of 45 and members of families in which multiple cancer had occurred. PATIENTS--Self referrals as well as patients referred by general and hospital practitioners. INTERVENTION--Relatives with a lifetime risk of 1 in 10 or greater (high risk group) were offered screening five yearly by colonoscopy, and those whose risk was between 1 in 10 and 1 in 17 were offered yearly screening for faecal occult blood. Women with family histories compatible with Lynch type II cancer family syndrome were offered screening for breast and pelvic tumours. RESULTS--In four years 715 patients were seen. Acceptance of screening was 90% (644 patients). Of 151 patients screened for faecal occult blood, two were found to have polyps. This screening test was unsatisfactory for the high risk group, having a negative predictive value of 78% in 59 patients tested. Regular screening by colonoscopy was offered to 382 high risk patients; 62 patients with polyps and five with colonic cancer were found. One hundred and ten pedigrees were identified with the Lynch type II cancer family syndrome, and four of 35 women screened were found to have breast cancer. Of 14 relatives aged over 65 with a 1 in 2 risk of site specific colonic cancer or Lynch type II cancer family syndrome, seven were found to have polyps, one of whom had carcinoma in situ. CONCLUSIONS--Family history can be used to identify those at risk of colonic cancer and to target appropriate screening. Colonoscopy detected a high number of premalignant colonic polyps, but faecal occult blood testing was unsatisfactory for those at high risk of colorectal cancer.