Search

Objectives: Currently, NICE recommends the use of faecal immunochemical test (FIT) at faecal haemoglobin concentrations (f-Hb) of 10 μg Hb/g faeces to stratify for colorectal cancer (CRC) risk in symptomatic populations. This f-Hb cut-off is advised across all analysers, despite the fact that a direct comparison of analyser performance, in a clinical setting, has not been performed., Methods: Two specimen collection devices (OC-Sensor, OC-S; HM-JACKarc, HM-J) were sent to 914 consecutive individuals referred for follow up due to their increased risk of CRC. Agreement of f-Hb around cut-offs of 4, 10 and 150 µg Hb/g faeces and CRC detection rates were assessed. Two OC-S devices were sent to a further 114 individuals, for within test comparisons., Results: A total of 732 (80.1%) individuals correctly completed and returned two different FIT devices, with 38 (5.2%) CRCs detected. Median f-Hb for individuals diagnosed with and without CRC were 258.5 and 1.8 µg Hb/g faeces for OC-S and 318.1 and 1.0 µg Hb/g faeces for HM-J respectively. Correlation of f-Hb results between OC-S/HM-J over the full range was rho=0.74, p<0.001. Using a f-Hb of 4 µg Hb/g faeces for both tests found an agreement of 88.1%, at 10 µg Hb/g faeces 91.7% and at 150 µg Hb/g faeces 96.3%. A total of 114 individuals completed and returned two OC-S devices; correlation across the full range was rho=0.98, p<0.001., Conclusions: We found large variations in f-Hb when different FIT devices were used, but a smaller variation when the same FIT device was used. Our data suggest that analyser-specific f-Hb cut-offs are applied with regard to clinical decision making, especially at lower f-Hb., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Background: New national guidance on urgent referral for investigation of colorectal cancer included faecal occult blood testing in 2015. A service evaluation of faecal immunochemical testing (FIT) and anaemia as risk stratification tools in symptomatic patients suspected of having CRC was undertaken., Methods: Postal FIT was incorporated into the colorectal cancer 2-week wait (2WW) pathway for all patients without rectal bleeding in 2016. Patients were investigated in the 2WW pathway as normal, and outcomes of investigations were recorded prospectively. Anaemia was defined as a haemoglobin level below 120 g/l in women and 130 g/l in men., Results: FIT kits were sent to 1106 patients, with an 80·9 per cent return rate; 810 patients completed investigations and 40 colorectal cancers were diagnosed (4·9 per cent). FIT results were significantly higher in patients with anaemia (median (i.q.r.) 4·8 (0·8-34·1) versus 1·2 (0-6·4) μg Hb/g faeces in those without anaemia; P  < 0·001). Some 60·4 per cent of patients (538 of 891) had a result lower than 4 μg haemoglobin (Hb) per g faeces (limit of detectability), and 69·7 per cent (621 of 891) had less than 10 μg Hb/g faeces. Some 60 per cent of patients with colorectal cancer had a FIT reading of 150 μg Hb/g faeces or more. For five colorectal cancers diagnosed in patients with a FIT value below 10 μg Hb/g faeces, there was either a palpable rectal mass or the patient was anaemic. A FIT result of more than 4 μg Hb/g faeces had 97·5 per cent sensitivity and 64·5 per cent specificity for a diagnosis of colorectal cancer. A FIT result above 4 μg Hb/g faeces and/or anaemia had a 100 per cent sensitivity and 45·3 per cent specificity for colorectal cancer diagnosis., Conclusion: FIT is most useful at the extremes of detectability; strongly positive readings predict high rates of colorectal cancer and other significant pathology, whereas very low readings in the absence of anaemia or a palpable rectal mass identify a group with very low risk. High return rates for FIT within this 2WW pathway indicate its acceptability.

Background: The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer chemoprevention, aligned with an excellent safety profile. Therefore, we aimed to test the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic colorectal neoplasia detected at colonoscopy., Methods: In a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial, patients aged 55-73 years who were identified during colonoscopy as being at high risk in the English Bowel Cancer Screening Programme (BCSP; ≥3 adenomas if at least one was ≥10 mm in diameter or ≥5 adenomas if these were <10 mm in diameter) were recruited from 53 BCSP endoscopy units in England, UK. Patients were randomly allocated (1:1:1:1) using a secure web-based server to receive 2 g EPA-free fatty acid (FFA) per day (either as the FFA or triglyceride), 300 mg aspirin per day, both treatments in combination, or placebo for 12 months using random permuted blocks of randomly varying size, and stratified by BCSP site. Research staff and participants were masked to group assignment. The primary endpoint was the adenoma detection rate (ADR; the proportion of participants with any adenoma) at 1 year surveillance colonoscopy analysed in all participants with observable follow-up data using a so-called at-the-margins approach, adjusted for BCSP site and repeat endoscopy at baseline. The safety population included all participants who received at least one dose of study drug. The trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN05926847., Findings: Between Nov 11, 2011, and June 10, 2016, 709 participants were randomly assigned to four treatment groups (176 to placebo, 179 to EPA, 177 to aspirin, and 177 to EPA plus aspirin). Adenoma outcome data were available for 163 (93%) patients in the placebo group, 153 (85%) in the EPA group, 163 (92%) in the aspirin group, and 161 (91%) in the EPA plus aspirin group. The ADR was 61% (100 of 163) in the placebo group, 63% (97 of 153) in the EPA group, 61% (100 of 163) in the aspirin group, and 61% (98 of 161) in the EPA plus aspirin group, with no evidence of any effect for EPA (risk ratio [RR] 0·98, 95% CI 0·87 to 1·12; risk difference -0·9%, -8·8 to 6·9; p=0·81) or aspirin (RR 0·99 (0·87 to 1·12; risk difference -0·6%, -8·5 to 7·2; p=0·88). EPA and aspirin were well tolerated (78 [44%] of 176 had ≥1 adverse event in the placebo group compared with 82 [46%] in the EPA group, 68 [39%] in the aspirin group, and 76 [45%] in the EPA plus aspirin group), although the number of gastrointestinal adverse events was increased in the EPA alone group at 146 events (compared with 85 in the placebo group, 86 in the aspirin group, and 68 in the aspirin plus placebo group). Six upper-gastrointestinal bleeding events were reported across the treatment groups (two in the EPA group, three in the aspirin group, and one in the placebo group)., Interpretation: Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence., Funding: Efficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Uptake of colorectal cancer screening is low in the English NHS Bowel Cancer Screening Programme (BCSP). Participation in screening is strongly associated with socioeconomic status. The aim of this study was to determine whether a supplementary leaflet providing the 'gist' of guaiac-based Faecal Occult Blood test (gFOBt) screening for colorectal cancer could reduce the socioeconomic status (SES) gradient in uptake in the English NHS BCSP., Methods: The trial was integrated within routine BCSP operations in November 2012. Using a cluster randomised controlled design all adults aged 59-74 years who were being routinely invited to complete the gFOBt were randomised based on day of invitation. The Index of Multiple Deprivation was used to create SES quintiles. The control group received the standard information booklet ('SI'). The intervention group received the SI booklet and the Gist leaflet ('SI + Gist') which had been designed to help people with lower literacy engage with the invitation. Blinding of hubs was not possible and invited subjects were not made aware of a comparator condition. The primary outcome was the gradient in uptake across IMD quintiles., Results: In November 2012, 163,525 individuals were allocated to either the 'SI' intervention (n = 79,104) or the 'SI + Gist' group (n = 84,421). Overall uptake was similar between the intervention and control groups (SI: 57.3% and SI + Gist: 57.6%; OR = 1.02, 95% CI: 0.92-1.13, p = 0.77). Uptake was 42.0% (SI) vs. 43.0% (SI + Gist) in the most deprived quintile and 65.6% vs. 65.8% in the least deprived quintile (interaction p = 0.48). The SES gradient in uptake was similar between the study groups within age, gender, hub and screening round sub-groups., Conclusions: Providing supplementary simplified information in addition to the standard information booklet did not reduce the SES gradient in uptake in the NHS BCSP. The effectiveness of the Gist leaflet when used alone should be explored in future research., Trial Registration: ISRCTN74121020 , registered: 17/20/2012.

Background: Uptake in the national colorectal cancer screening programme in England varies by socioeconomic status. We assessed four interventions aimed at reducing this gradient, with the intention of improving the health benefits of screening., Methods: All people eligible for screening (men and women aged 60-74 years) across England were included in four cluster-randomised trials. Randomisation was based on day of invitation. Each trial compared the standard information with the standard information plus the following supplementary interventions: trial 1 (November, 2012), a supplementary leaflet summarising the gist of the key information; trial 2 (March, 2012), a supplementary narrative leaflet describing people's stories; trial 3 (June, 2013), general practice endorsement of the programme on the invitation letter; and trial 4 (July-August, 2013) an enhanced reminder letter with a banner that reiterated the screening offer. Socioeconomic status was defined by the Index of Multiple Deprivation score for each home address. The primary outcome was the socioeconomic status gradient in uptake across deprivation quintiles. This study is registered, number ISRCTN74121020., Findings: As all four trials were embedded in the screening programme, loss to follow-up was minimal (less than 0·5%). Trials 1 (n=163,525) and 2 (n=150,417) showed no effects on the socioeconomic gradient of uptake or overall uptake. Trial 3 (n=265 434) showed no effect on the socioeconomic gradient but was associated with increased overall uptake (adjusted odds ratio [OR] 1·07, 95% CI 1·04-1·10, p<0·0001). In trial 4 (n=168 480) a significant interaction was seen with socioeconomic status gradient (p=0·005), with a stronger effect in the most deprived quintile (adjusted OR 1·11, 95% CI 1·04-1·20, p=0·003) than in the least deprived (1·00, 0·94-1·06, p=0·98). Overall uptake was also increased (1·07, 1·03-1·11, p=0·001)., Interpretation: Of four evidence-based interventions, the enhanced reminder letter reduced the socioeconomic gradient in screening uptake, but further reducing inequalities in screening uptake through written materials alone will be challenging., Funding: National Institute for Health Research., (Copyright © 2016 Wardle et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Background: There is a socioeconomic gradient in the uptake of screening in the English NHS Bowel Cancer Screening Programme (BCSP), potentially leading to inequalities in outcomes. We tested whether endorsement of bowel cancer screening by an individual's general practice (GP endorsement; GPE) reduced this gradient., Methods: A cluster-randomised controlled trial. Over 20 days, individuals eligible for screening in England from 6480 participating general practices were randomly allocated to receive a GP-endorsed or the standard invitation letter. The primary outcome was the proportion of people adequately screened and its variation by quintile of Index of Multiple Deprivation., Results: We enrolled 265,434 individuals. Uptake was 58.2% in the intervention arm and 57.5% in the control arm. After adjusting for age, sex, hub and screening episode, GPE increased the overall odds of uptake (OR=1.07, 95% CI 1.04-1.10), but did not affect its socioeconomic gradient. We estimated that implementing GPE could result in up to 165 more people with high or intermediate risk colorectal adenomas and 61 cancers detected, and a small one-off cost to modify the standard invitation (£78,000)., Conclusions: Although GPE did not improve its socioeconomic gradient, it offers a low-cost approach to enhancing overall screening uptake within the NHS BCSP.

Background: The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials., Design: The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2×2 factorial 'efficacy' study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55-73 year-old patients, who have been identified as 'high risk' (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and 'advanced') per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as 'intermediate risk' for future surveillance. Exploratory end-points include levels of bioactive lipid mediators such as ω-3 PUFAs, resolvin E1 and PGE-M in plasma, urine, erythrocytes and rectal mucosa in order to gain insights into the mechanism(s) of action of EPA and aspirin, alone and in combination, as well as to discover predictive biomarkers of chemopreventive efficacy. The recruitment target is 904 patients., Trial Registration: Current Controlled Trials ISRCTN05926847.

Introduction: The Bowel Cancer Screening Programme in England began operating in 2006 with the aim of full roll out across England by December 2009. Subjects aged 60-69 are being invited to complete three guaiac faecal occult blood tests (6 windows) every 2 years. The programme aims to reduce mortality from colorectal cancer by 16% in those invited for screening., Methods: All subjects eligible for screening in the National Health Service in England are included on one database, which is populated from National Health Service registration data covering about 98% of the population of England. This analysis is only of subjects invited to participate in the first (prevalent) round of screening., Results: By October 2008 almost 2.1 million had been invited to participate, with tests being returned by 49.6% of men and 54.4% of women invited. Uptake ranged between 55-60% across the four provincial hubs which administer the programme but was lower in the London hub (40%). Of the 1.08 million returning tests 2.5% of men and 1.5% of women had an abnormal test. 17,518 (10,608 M, 6910 F) underwent investigation, with 98% having a colonoscopy as their first investigation. Cancer (n=1772) and higher risk adenomas (n=6543) were found in 11.6% and 43% of men and 7.8% and 29% of women investigated, respectively. 71% of cancers were 'early' (10% polyp cancer, 32% Dukes A, 30% Dukes B) and 77% were left-sided (29% rectal, 45% sigmoid) with only 14% being right-sided compared with expected figures of 67% and 24% for left and right side from UK cancer registration., Conclusion: In this first round of screening in England uptake and fecal occult blood test positivity was in line with that from the pilot and the original European trials. Although there was the expected improvement in cancer stage at diagnosis, the proportion with left-sided cancers was higher than expected.

Background: Bowel cancer is a serious health burden and its early diagnosis improves survival. The Bowel Cancer Screening Programme (BCSP) in England screens with the Faecal Occult Blood test (FOBt), followed by colonoscopy for individuals with a positive test result. Socioeconomic inequalities have been demonstrated for FOBt uptake, but it is not known whether they persist at the next stage of the screening pathway. The aim of this study was to assess the association between colonoscopy uptake and area socioeconomic deprivation, controlling for individual age and sex, and area ethnic diversity, population density, poor self-assessed health, and region., Methods: Logistic regression analysis of colonoscopy uptake using BCSP data for England between 2006 and 2009 for 24 180 adults aged between 60 and 69 years., Results: Overall colonoscopy uptake was 88.4%. Statistically significant variation in uptake is found between quintiles of area deprivation (ranging from 86.4 to 89.5%), as well as age and sex groups (87.9-89.1%), quintiles of poor self-assessed health (87.5-89.5%), non-white ethnicity (84.6-90.6%) and population density (87.9-89.3%), and geographical regions (86.4-90%)., Conclusion: Colonoscopy uptake is high. The variation in uptake by socioeconomic deprivation is small, as is variation by subgroups of age and sex, poor self-assessed health, ethnic diversity, population density, and region.

Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term posttrial follow-up of nearly 14,000 patients from four randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about five years was associated with a 34% reduction in 20-year CRC mortality. A separate metaanalysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in four randomized adenoma prevention trials showed that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least two years, there was a 50% or more reduction in the risk of CRC commencing five years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin's anticancer effect require further investigation., (©2011 AACR.)

Aim: Antioxidants, such as vitamin A, C and E, selenium and β-carotene, have been proposed as possible agents in the chemoprevention of colorectal cancer and have been the subject of recent trials and reviews. This review aimed to assess the present evidence on the effect of antioxidants on the incidence of colorectal neoplasms in the general population., Method: A systematic review of randomized controlled trials was undertaken comparing antioxidants alone or in combination with other agents vs placebo. The following databases were searched for published and unpublished literature: Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science, and Biological Abstracts and Research Registers. Studies were quality appraised and extracted. Meta-analysis was performed., Results: Twelve studies were identified as relevant. In the nine comparing antioxidants with no antioxidants (n=148 922), there was no difference in the incidence of colorectal cancer [relative risk (RR) 1.00, 95% confidence interval (CI) 0.88-1.13]. One study assessed the effect of antioxidants on adenoma formation (n=15 538) and did not demonstrate a statistically significant effect (RR 1.47, 95% CI 0.97-2.23). Of 14 discrete analyses for different combinations of antioxidants, only one reported a statistically significant increase in relative risk of adenoma formation in participants receiving vitamin E (RR 1.74, 95% CI 1.09-1.79, P=0.02) or vitamin E plus β-carotene (RR 1.63, 95% CI 1.01-2.63, P=0.04). Effectiveness did not seem to differ between healthy populations, participants with cardiovascular risk factors or populations exposed to smoking or asbestos., Conclusion: The review demonstrates that antioxidants (vitamin A, C and E, selenium and β-carotene), as single agents, in combination with other antioxidants or in combination with other agents, are not effective in the chemoprevention of colorectal neoplasia in the general population. This questions their involvement in future randomized controlled trials of chemoprevention in colorectal cancer., (© 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.)

The risk of developing colorectal cancer is increased in patients with inflammatory bowel disease (IBD). Surveillance colonoscopy has not been shown to prolong survival and rates of interval cancer are reported to be high. Various chemopreventive agents have been clearly shown to reduce the risk of colorectal adenoma and cancer in the general population and the problems associated with colonoscopic surveillance have led to increasing interest in utilising chemopreventive strategies to reduce the risk of colorectal cancer in patients with inflammatory bowel disease as well. Continuing colonic inflammation has been shown to be important in the development of colorectal cancer and therefore anti-inflammatory agents have been considered potential chemopreventive agents. As present no agents have been shown to have indisputable chemopreventive activity in IBD but 5-ASAs and thiopurine analogues by reducing inflammation are likely to have some chemopreventive activity and will often be indicated for disease control. More studies are needed using agents such as aspirin and calcium which have been shown to be chemopreventive in sporadic colorectal neoplasia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Observational data suggest that lower folate status is associated with an increased risk of colorectal neoplasia, implying that folate may be useful as a chemopreventive agent. We conducted a combined analysis of three large randomized trials of folic acid supplementation for the prevention of metachronous adenomas in patients with an adenoma history. Participants included 2,632 men and women who had a history of adenomas randomized to either 0.5 or 1.0 mg/day of folic acid or placebo and who had a follow-up endoscopy 6 to 42 months after randomization [mean = 30.6 (standard deviation = 8.1) months]. We used random-effects meta-analysis to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The RR comparing folic acid versus placebo was 0.98 (95% CI = 0.82-1.17) for all adenomas and 1.06 (95% CI = 0.81-1.39) for advanced lesions. Folic acid was associated with a nonsignificant decreased risk of any adenoma among subjects in the lowest quartile of baseline plasma folate (≤ 11 nmol/L) and no effect among individuals in the highest quartile (> 29 nmol/L, p for trend = 0.17). There was a nonsignificant trend of decreasing risk of any adenoma associated with folic acid supplements with increasing alcohol intake. During the early follow-up reported here, more deaths occurred in the placebo group than in the folic acid group (1.7% vs. 0.5%, p = 0.002). In conclusion, after up to 3.5 years of folic acid use, there is no clear decrease or increase in the occurrence of new adenomas in patients with a history of adenoma., (Copyright © 2010 UICC.)

Background: An organized, population-based, colorectal cancer screening programme was initiated in England in 2006 offering biennial faecal occult blood testing (FOBT) to adults aged 60-69 years. Organized screening programmes with no associated financial costs to the individual should minimize barriers to access for lower socio-economic status (SES) groups. However, SES differences in uptake were observed in the pilot centres of the UK programme, so the aim of this analysis was to identify the extent of inequalities in uptake by SES, ethnic diversity, gender and age in the first 28 months of the programme. Design Cross-sectional analysis of colorectal cancer screening uptake data., Methods: Between October 2006 and January 2009, over 2.6 million adults aged 60-69 years were mailed a first FOBT kit by the five regional screening hubs. Uptake was defined as return of a test kit within 13 weeks. We used multivariate generalized linear regression to examine variation by area-based socioeconomic deprivation, area-based ethnicity, gender and age., Results: Uptake was 54%, but showed a gradient across quintiles of deprivation, ranging from 35% in the most deprived quintile to 61% in the least deprived. Multivariate analyses confirmed an independent effect of deprivation, with stronger effects in women and older people. The most ethnically diverse areas also had lower uptake (38%) than other areas (52-58%) independent of SES, age, gender and regional screening hub. Ethnic disparities were more pronounced in men but equivalent across age groups. More women than men returned a kit (56 vs 51%), but there was also an interaction with age, with uptake increasing with age in men (49% at 60-64 years; 53% at 65-69 years) but not women (57 vs 56%)., Conclusions: Overall uptake rates in this organized screening programme were encouraging, but nonetheless there was low uptake in the most ethnically diverse areas and a striking gradient by SES. Action to promote equality of uptake is needed to avoid widening inequalities in cancer mortality.

Background: Colorectal cancer (CRC) is the third most common cancer in the UK: incidence increases with age, median age at diagnosis being over 70 years. Approximately 25% of cases occur in individuals with a family history of CRC, including 5% caused by familial adenomatous polyposis (FAP) or hereditary non-polyposis CRC (HNPCC). Most develop from adenomatous polyps arising from the intestine lining. Individuals with these polyps undergo polypectomy and are invited for endoscopic surveillance. Screening via faecal occult blood testing has been rolled out across the UK., Objectives: To evaluate the clinical effectiveness and cost-effectiveness of drug and micronutrient interventions for the prevention of CRC and/or adenomatous polyps. Interventions considered include: non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclo-oxygenase-2 (COX-2) inhibitors; folic acid; calcium; vitamin D and antioxidants (including vitamin A, vitamin C, vitamin E, selenium and beta-carotene). Chemoprevention was assessed in the general population, in individuals at increased risk of CRC, and in individuals with FAP or HNPCC., Data Sources: A systematic review identified randomised controlled trials (RCTs) assessing drug and nutritional agents for the prevention of CRC or adenomatous polyps. A separate search identified qualitative studies relating to individuals' views, attitudes and beliefs about chemoprevention. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CINAHL, the Cochrane Database of Systematic Reviews, Cochrane CENTRAL Register of Controlled Trials, DARE, NHS-EED (NHS Economic Evaluation Database), HTA database, Science Citation Index, BIOSIS previews and the Current Controlled Trials research register were searched in June 2008. Data were extracted by one reviewer and checked by a second., Review Methods: The synthesis methods used were systematic review and meta-analysis for RCTs and qualitative framework synthesis for qualitative studies. A health economic model was developed to assess the cost-effectiveness of chemoprevention for two populations with different levels of risk of developing CRC: the general population and an intermediate-risk population., Results: The search identified 44 relevant RCTs and six ongoing studies. A small study of aspirin in FAP patients produced no statistically significant reduction in polyp number but a possible reduction in polyp size. There was a statistically significant 21% reduction in risk of adenoma recurrence [relative risk (RR) 0.79, 95% confidence interval (CI) 0.68 to 0.92] in an analysis of aspirin versus no aspirin in individuals with a history of adenomas or CRC. In the general population, a significant 26% reduction in CRC incidence was demonstrated in studies with a 23-year follow-up (RR 0.74, 95% CI 0.57 to 0.97). Non-aspirin NSAID use in FAP individuals produced a non-statistically significant reduction in adenoma incidence after 4 years of treatment and follow-up and reductions in polyp number and size. In individuals with a history of adenomas there was a statistically significant 34% reduction in adenoma recurrence risk (RR 0.66, 95% CI 0.60 to 0.72) and a statistically significant 55% reduction in advanced adenoma incidence (RR 0.45, 95% CI 0.35 to 0.58). No studies assessed the effect of non-aspirin NSAIDs in the general population. There were no studies of folic acid in individuals with FAP or HNPCC. There was no significant effect of folic acid versus placebo on adenoma recurrence (RR 1.16, 95% CI 0.97 to 1.39) or advanced adenoma incidence in individuals with a history of adenomas. In the general population there was no significant effect of folic acid on risk of CRC (RR 1.13, 95% CI 0.77 to 1.64), although studies were of relatively short duration. Calcium use by FAP patients produced no significant reduction in polyp number or disease progression. In individuals with a history of adenomas there was a statistically significant 18% reduction in risk of adenoma recurrence (RR 0.82, 95% CI 0.69 to 0.98) and a non-significant reduction in risk of advanced adenomas (RR 0.77, 95% CI 0.50 to 1.17). In the general population there was no significant effect of calcium on risk of CRC (RR 1.08, 95% CI 0.87 to 1.34), although studies were of relatively short duration. There were no studies of antioxidant use in individuals with FAP or HNPCC, and in individuals with a history of adenomas no statistically significant differences in relative risk of adenoma recurrence were found. In the general population there was no difference in incidence of CRC (RR 1.00, 95% CI 0.88 to 1.13) with antioxidant use compared with no antioxidant use. Twenty studies reported qualitative findings concerning chemoprevention. People are more likely to use NSAIDs if there is a strong perceived need. Perceptions of risk and benefit also influence decision-making and use. People have fewer concerns about using antioxidants or other supplements, but their perception of the benefits of these agents is less well-defined. The model analysis suggested that the most cost-effective age-range policy in the general population would be to provide chemoprevention to all individuals within the general population from age 50 to 60 years. The use of aspirin in addition to screening within the general population is likely to result in a discounted cost per life-year gained of around 10,000 pounds and a discounted cost per quality-adjusted life-year (QALY) gained of around 23,000 pounds compared with screening alone. In the intermediate-risk group the most economically viable age-range policy would be to provide chemoprevention to individuals following polypectomy aged 61 to 70 years. Calcium is likely to have a discounted cost per QALY gained of around 8000 pounds compared with screening alone. Although aspirin in addition to screening should be more effective and less costly than screening alone, under the current assumptions of benefits to harms of aspirin and calcium, aspirin is expected to be extendedly dominated by calcium., Limitations: Whilst a number of studies were included in the review, the duration of follow-up was generally insufficient to detect an effect on cancer incidence. Given the uncertainties and ambiguities in the evidence base, the results of the health economic analysis should be interpreted with caution., Conclusions: Aspirin and celecoxib may reduce recurrence of adenomas and incidence of advanced adenomas in individuals with an increased risk of CRC and calcium may reduce recurrence of adenomas in this group. COX-2 inhibitors may decrease polyp number in patients with FAP. There is some evidence for aspirin reducing the incidence of CRC in the general population. Both aspirin and NSAIDs are associated with adverse effects so it will be important to consider the risk-benefit ratio before recommending these agents for chemoprevention. The economic analysis suggests that chemoprevention has the potential to represent a cost-effective intervention, particularly when targeted at intermediate-risk populations following polypectomy.

Background: Multiple lines of evidence indicate that aspirin has an antineoplastic effect in the large bowel. Randomized clinical trials have been conducted to evaluate the effectiveness of aspirin for reducing the risk of colorectal adenomas. A meta-analysis of these trials will provide more precise estimates of the aspirin effect, both overall and in subgroups., Methods: We combined data from all randomized double-blind placebo-controlled trials that evaluated aspirin for the prevention of colorectal adenomas. We used random-effects meta-analysis to estimate risk ratios and 95% confidence intervals (CIs) for the effect of aspirin on the occurrence of adenomas and of advanced lesions (ie, tubulovillous adenomas, villous adenomas, adenomas >or=1 cm in diameter, adenomas with high-grade dysplasia, or invasive cancer). All statistical tests were two-sided., Results: We identified four clinical trials with 2967 randomly assigned participants. Each trial evaluated aspirin for the secondary prevention of colorectal adenomas. Doses of aspirin tested ranged from 81 to 325 mg/d. The average age of participants at baseline was 58 years, and 60% were male. Median follow-up was 33 months. A total of 2698 participants underwent colonoscopic follow-up and were included in the analysis of adenoma occurrence and advanced-lesion occurrence after randomization. Among these participants, adenomas were found in 424 (37%) of the 1156 participants allocated to placebo and in 507 (33%) of the 1542 participants allocated to any dose of aspirin. Advanced lesions were found in 12% of participants in the placebo group and in 9% of participants allocated to any dose of aspirin. The pooled risk ratio of any adenoma for any dose of aspirin vs placebo was 0.83 (95% CI = 0.72 to 0.96). This corresponded to an absolute risk reduction of 6.7% (95% CI = 3.2% to 10.2%). For any advanced lesion, the pooled risk ratio was 0.72 (95% CI = 0.57 to 0.90). We found no statistically significant effect modification for any of the baseline factors studied., Conclusion: Aspirin is effective for the prevention of colorectal adenomas in individuals with a history of these lesions.

Vitamin D receptor (VDR) activation inhibits proliferation and angiogenesis in the colorectal epithelium, and inhibits metastasis of colorectal tumors. Polymorphisms in the VDR gene alter receptor cellular levels and functioning, and may confer altered susceptibility to colorectal neoplasia. We aimed to investigate the influence of VDR polymorphisms and dietary factors impacting on vitamin D metabolism on colorectal adenoma (CRA) recurrence. Data on dietary intakes of calcium, vitamin D and dairy products were collected from 853 participants in the United Kingdom Colorectal Adenoma Prevention trial, a randomized trial of aspirin and folate for CRA recurrence prevention. The VDR Cdx2, FokI, BsmI, ApaI and TaqI polymorphisms were genotyped in 546 participants with available DNA, and gene-diet interaction analyses performed in 480. Dairy product intake was inversely related to CRA recurrence risk independent of calcium and vitamin D [relative risk (RR) = 0.64; 95% confidence intervals (CIs): 0.47-0.88, for subjects in the highest compared to lowest intake tertile, p(trend) = 0.005]. Milk accounted for 60% of dairy product intake, and on analysis of milk and nonmilk dairy products separately recurrence risk in individuals in the highest tertile of milk intake was half that of lowest tertile individuals (RR = 0.52; 95% CI: 0.38-0.72, p(trend) = 3.2 x 10(-5)), whereas nonmilk dairy products did not influence recurrence. VDR polymorphism genotypes and haplotypes did not directly alter recurrence risk, but the reduction in risk associated with high dairy product intake was confined to individuals with ApaI aA/AA genotype (p(interaction) = 0.02). These findings indicate dairy products, and in particular milk, have chemopreventive activity against CRA recurrence.

Purpose: The chemopreventive activity of aspirin in colorectal neoplasia may be explained in part by its effect on polyamine metabolism. The ornithine decarboxylase (ODC) G316A polymorphism affects polyamine metabolism through altered expression of ODC. We investigated the influence of ODC G316A on the chemopreventive activity of aspirin in colorectal adenoma (CRA) recurrence., Experimental Design: We genotyped ODC G316A in 546 individuals in the United Kingdom Colorectal Adenoma Prevention trial of aspirin for CRA recurrence prevention and pooled our findings with data from two other randomized intervention trials., Results: The United Kingdom Colorectal Adenoma Prevention participants with homozygous ODC 316AA genotype were at reduced CRA recurrence risk [relative risk (RR), 0.43; 95% confidence interval (95% CI), 0.16-1.15], particularly if also exposed to aspirin (RR, 0.24; 95% CI, 0.03-1.71). In the pooled analysis of 2,207 individuals, those with homozygous ODC 316AA genotype were at significantly reduced CRA recurrence risk (RR, 0.68; 95% CI, 0.47-0.99). Following stratification by genotype and aspirin exposure, individuals with homozygous wild-type or heterozygous genotypes derived modest benefit from aspirin (RR, 0.85; 95% CI, 0.72-1.01), whereas in those with both ODC 316AA genotype and aspirin exposure recurrence risk was halved (RR, 0.52; 95% CI, 0.29-0.91)., Conclusion: The ODC G316A genotype is prognostic for CRA recurrence and predictive of an enhanced response to aspirin in preventing recurrence. This variant has the potential to be a clinically useful genetic marker to identify individuals likely to derive the greatest benefit from aspirin chemoprevention.

Background & Aims: Although observational studies have found regular aspirin use to be associated with a reduced risk of colorectal neoplasia, results from randomized trials using aspirin have been inconsistent. Dietary folate intake also has been found to be associated with a reduced risk of colorectal neoplasms in observational studies., Methods: A multicenter, randomized, double-blind trial of aspirin (300 mg/day) and folate supplements (0.5 mg/day) to prevent colorectal adenoma recurrence was performed using a 2 x 2 factorial design. All patients had an adenoma (>/=0.5 cm) removed in the 6 months before recruitment and were followed-up at 4-month intervals with a second colonoscopy after approximately 3 years. The primary outcome measure was a colorectal adenoma diagnosed after baseline., Results: A total of 945 patients were recruited into the study, of whom 853 (90.3%) underwent a second colonoscopy. In total, 99 (22.8%) of 434 patients receiving aspirin had a recurrent adenoma compared with 121 (28.9%) of 419 patients receiving placebo (relative risk, 0.79; 95% confidence interval [CI], 0.63-0.99). A total of 104 patients developed an advanced colorectal adenoma; 41 (9.4%) of these were in the aspirin group and 63 (15.0%) were in the placebo group (relative risk, 0.63; 95% CI, 0.43-0.91). Folate supplementation was found to have no effect on adenoma recurrence (relative risk, 1.07; 95% CI, 0.85-1.34)., Conclusions: Aspirin (300 mg/day) but not folate (0.5 mg/day) use was found to reduce the risk of colorectal adenoma recurrence, with evidence that aspirin could have a significant role in preventing the development of advanced lesions.

The effects of polymorphisms in genes coding for key folate metabolism enzymes such as thymidylate synthetase (TS) on colorectal neoplasia risk are likely to be influenced by gene-gene and gene-nutrient interactions. We investigated the combined effects of three polymorphisms in the TS gene region, TSER, TS 3R G>C, and TS 1494del6, dietary intakes of folate and other B vitamins, and genotype for other folate metabolism variants, in a colorectal adenoma (CRA) case-control study. Individuals homozygous for TS 1494del6 del/del were at significantly reduced CRA risk compared to those with either ins/del or ins/ins genotypes (odds ratio 0.52; 95% confidence interval: 0.31-0.85, P=0.009). We also observed evidence of interactions between TS 1494del6 genotype and intake of folate, and vitamins B6 and B12, and MTHFR C677T genotype, with the reduction in risk in del/del homozygotes being largely confined to individuals with high nutrient intakes and MTHFR 677CC genotype (P interaction=0.01, 0.006, 0.03, and 0.07, respectively). TSER genotype, when considered either alone or in combination with TS 3R G>C genotype, did not significantly influence CRA risk. These findings support a role for TS in colorectal carcinogenesis, and provide further evidence that functional polymorphisms in folate metabolism genes act as low-risk alleles for colorectal neoplasia and participate in complex gene-gene and gene-nutrient interactions.

Background and Aims: Several studies suggest that statins prevent some cancers, with one study finding a 47% reduction in colorectal cancer risk after >or=5 years of regular use., Methods: A nested case-control study was conducted within 454 general practices in the United Kingdom using the QRESEARCH database. Cases with colorectal cancer were diagnosed between 1995 and 2005. The effects of statins, nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, and aspirin on colorectal cancer were estimated with conditional logistic regression adjusted for morbidity, smoking status, body mass index, and socioeconomic status., Results: We analyzed 5686 cases and 24,982 matched controls with >or=4 years of records. The adjusted odds ratio for colorectal cancer associated with any statin prescription was 0.93 (95% confidence interval: 0.83-1.04), with no trend in duration of use or number of prescriptions. For any nonsteroidal anti-inflammatory drug prescription the adjusted odds ratio was 0.94 (95% confidence interval: 0.88-1.00), with a significant decrease in risk with increasing number of prescriptions and an adjusted odds ratio of 0.76 (0.60-0.95) for >or=25 prescriptions. Prolonged use of cyclooxygenase-2 inhibitors was minimal, but for those receiving >or=25 prescriptions the adjusted odds ratio was 0.34 (0.14-0.85). Results were similar in the subset of participants with >or=8 years of records; the adjusted odds ratio for >or=61 months of statin prescriptions was 1.00 (0.67-1.48)., Conclusions: In this large population-based case-control study prolonged use of nonsteroidal anti-inflammatory drug and cyclooxygenase-2 inhibitor was associated with a reduced colorectal cancer risk, but prolonged statin use was not.

Purpose: The UDP glucuronosyltransferase 1A6 (UGT1A6) and cytochrome P450 2C9 (CYP2C9) enzymes participate in the metabolism of nonsteroidal anti-inflammatory drugs, endogenous substances, and carcinogens. Functional polymorphisms of UGT1A6 (T181A and R184S) and CYP2C9 (R144C and I359L) have been reported to modify the protective effect of aspirin on colorectal adenoma risk. We aimed to further investigate the effect of these genetic variants on the development of colorectal neoplasia., Experimental Design: We examined the relationship between UGT1A6 and CYP2C9 genotype and colorectal adenoma recurrence in 546 patients participating in a randomized placebo-controlled aspirin intervention trial., Results: Although colorectal adenoma recurrence was not significantly influenced by CYP2C9 genotype, carriers of variant UGT1A6 alleles were at significantly reduced risk of colorectal neoplasia recurrence [relative risk (RR), 0.68; 95% confidence interval (95% CI), 0.52-0.89]. This risk reduction was also evident when the analysis was confined to advanced neoplasia recurrence (RR, 0.71; 95% CI, 0.47-1.09). When patients were stratified by genotype and aspirin intervention, those with variant UGT1A6 alleles were at reduced recurrence risk irrespective of whether they received aspirin or placebo (RR, 0.62; 95% CI, 0.42-0.92 and RR, 0.63; 95% CI, 0.44-0.91, respectively)., Conclusions: These findings confirm that UGT1A6 variants influence colorectal carcinogenesis independent of aspirin intake and suggest that they may have clinical value in secondary prevention programs for patients diagnosed with colorectal adenoma.

Folate intake is inversely related to risk of developing colorectal neoplasia. Associations between risk of colorectal neoplasia and polymorphisms in genes coding for enzymes involved in folate metabolism have also been reported, suggesting a relationship between genotype and development of colorectal neoplasia. To further investigate the effects of folate metabolism genotypes on colorectal neoplasia, we genotyped 546 patients participating in a randomized controlled trial of folate supplementation for the prevention of colorectal adenoma recurrence. A significantly reduced risk of recurrence was observed in patients heterozygous for the MTRR A66G polymorphism [relative risk (RR), 0.64; 95% confidence interval (95% CI), 0.46-0.90] or heterozygous for the MTHFR A1298C polymorphism (RR, 0.71; 95% CI, 0.52-0.97). Furthermore, a significant reduction in recurrence risk was seen in MTRR A66G heterozygotes who received folate supplements but not in those who did not receive folate. Patients heterozygous for the MTHFR C677T polymorphism had a nonsignificant risk reduction (RR, 0.92; 95% CI, 0.69-1.23), as did patients with one or two variant alleles for the MTR A2756G polymorphism (RR, 0.82; 95% CI, 0.60-1.12). No influence on recurrence risk was observed for the TSER, TSER 3R G>C, and TS 1494del6 variants. These findings provide additional support for the hypothesis that germ line variants in folate metabolism genes influence the development of colorectal adenomas.

Background and Aims: The objective of this study was to evaluate the risk of colorectal cancer (CRC) in patients taking aminosalicylates (5-ASA) for inflammatory bowel disease (IBD)., Methods: The General Practice Research Database (GPRD) which contains the primary care records of five million people in the UK was used to identify users of mesalazine, balsalazide, olsalazine, or sulfasalazine with a history of IBD. In a nested case control analysis, each incident CRC case with any use of a 5-ASA in the six months before the CRC diagnosis was matched by age, sex, and calendar time to six control patients who were also currently using a 5-ASA. Patients were then classified according to regularity of use. The analysis was controlled for body mass index, IBD duration, history of colorectal polyps, use of non-steroidal anti-inflammatory drugs, paracetamol, aspirin, immunosuppressants, oral and rectal glucocorticoids, prior gastrointestinal hospitalisation, recorded colonoscopy, and number of visits to the general practitioner for IBD symptoms in the 6-24 months before diagnosis., Results: The study population included 18 969 patients, of whom 100 had developed CRC during 5-ASA exposure. Most of these cases had a history of ulcerative colitis (76 patients). In the case control analysis, regular users, defined as having six or more 5-ASA prescriptions in the previous 12 months, were found to have a decreased risk of CRC compared with irregular users (crude odds ratio (OR) 0.7 (0.44-1.03); adjusted OR 0.60 (0.38-0.96)). Regular users of sulfasalazine with 6-12 prescriptions before had an adjusted OR of 0.95 (0.22-4.11); with 13-30 prior prescriptions this was 0.41 (0.14-1.20) and with >30 prior prescriptions this was 0.77 (0.37-1.60). For mesalazine users, these values were 1.13 (0.49-2.59), 0.30 (0.11-0.83), and 0.31 (0.11-0.84), respectively., Conclusion: These results show that regular 5-ASA use is associated with some reduction in the risk of CRC developing in ulcerative colitis.

Background: The relationship between Barrett's oesophagus and colorectal cancer and other extra-oesophageal malignancies (EOM) has been a matter of controversy. These relationships have therefore been examined in a prospective study design in the General Practice Research Database., Methods: Cohorts of patients having Barrett's oesophagus (n=1677), oesophagitis (n=6392), and simple reflux (n=6328), and a standard reference cohort representing the general population in the UK (n=13,416) were selected. The last three cohorts were matched to the Barrett's cohort by general practice, age and sex. Incident outcomes occurring beyond the first year of the follow-up were used for analyses. Hazard ratios and 95% confidence intervals were calculated using Cox's proportional hazards regression. The associations with cataract and oesophageal cancer were explored for comparison., Results: Incident cases of 567 EOM (including 74 colorectal cancers), 448 cataract and 43 oesophageal cancers were used in the final analysis. The relative risks for colorectal cancer compared to the standard reference cohort were 1.16 (0.42-3.21) in the Barrett's cohort, 1.39 (0.76-2.54) in the oesophagitis cohort, and 0.93 (0.45-1.90) in the simple reflux cohort. The corresponding relative risks in the Barrett's cohort were 1.29 (0.90-1.85), 1.60 (1.10-2.32), and 10.56 (5.07-21.99) for EOM, cataract and oesophageal cancer, respectively., Conclusions: The risk of colorectal cancer was not higher in any of the Barrett's oesophagus, oesophagitis, or reflux cohorts compared to the general population. The explanations for the modest increase in the risk of EOM and cataract in the above cohorts are unclear but they may be mediated by ascertainment bias or shared risk factors.

Purpose: The results of previous studies of colorectal neoplasia and fecal composition have been inconsistent, in part because the cases have been symptomatic and the studies small. We sought to test hypotheses relating to fecal bile acids, calcium, and pH in a large sample of asymptomatic subjects who had participated in fecal occult blood screening., Methods: Fecal samples were obtained from 45 cases of cancer, 129 subjects with adenoma, 167 fecal occult blood-negative controls and 155 fecal occult blood-positive subjects in whom no cancer or adenoma was found. Concentrations of fecal bile acids, steroids, calcium, and pH were assessed blind to case-control status and compared between cases and 1) fecal occult blood-negative controls and 2) fecal occult blood-positive subjects., Results: No association between colorectal cancer and fecal bile acids or pH was observed. Although there was no overall association between colorectal adenomas and fecal bile acids or pH, villous adenomas were associated with increasing concentrations of major bile acids and decreasing concentration of minor bile acids, and there was a suggestion of an inverse association with an acid pH. High levels of fecal calcium were associated with a reduced risk of both colorectal cancer and adenoma, but this was not statistically significant., Conclusion: The study does not support an association between colorectal cancer and fecal bile acids or pH. However, there is evidence that increases in major bile acids are associated with villous adenomas.

Objectives: Inflammatory bowel disease (IBD) is usually diagnosed as a result of symptoms but occasionally is found during investigation for other conditions. An earlier report from Nottingham had found a high prevalence of previously undetected "asymptomatic" IBD detected as a result of colorectal cancer screening, and the aim of this study was to reassess the prevalence, symptoms, and outcome in these patients., Methods: We investigated subjects found to be fecal occult blood (FOB) positive in a randomized trial of FOB screening for colorectal cancer. All FOB-positive subjects were investigated by colonoscopy or flexible sigmoidoscopy and barium enema. Subjects with IBD were referred back to their general practitioner for any further investigation and treatment., Results: Seventy-five thousand two hundred fifty-three subjects (aged 45-74) were sent FOB tests and 44,838 (60%) completed a series of tests on one or more occasions. Of 133,000 test series, 1.5% were positive. During investigation 53 cases of previously undetected IBD (52 of ulcerative colitis) were found; 52% (27/52) had proctosigmoiditis only, whereas 25% (13/52) had pancolitis. Only 17% (9/52) were completely asymptomatic, with a half or more reporting some rectal bleeding (54%) or diarrhea (50%). The overall prevalence of undetected ulcerative colitis was 69/10(5) (95% CI = 50-88/10(5)) in people offered screening and 116/10(5) (95% CI = 85-147/10(5)) in people accepting screening and was higher in men. Of 32 subjects followed up 2-12 yr after diagnosis, 91% (29) continued to have few or no symptoms, with only 12 currently receiving any treatment for their colitis., Conclusions: In comparison with detected disease, undetected ulcerative colitis is relatively common but does usually cause some symptoms. It generally appears to follow a benign course, but a significant proportion have extensive colitis and may therefore be at an increased risk of colorectal cancer.

Background and Aims: In the USA and many other countries, endoscopic surveillance of colorectal adenoma patients is now widely practised. However, the optimal frequency and mode of such surveillance are not yet established. The aim of this trial was to compare surveillance at one, two, or five year intervals using either flexible sigmoidoscopy or colonoscopy., Methods: Analysis of a randomised trial of flexible sigmoidoscopy and colonoscopy over one, two, or five years after stratification for "high" or "low" risk of recurrent adenomas. The trial started in 1984., Results: A total of 776 patients were stratified into "high" (n=307) and "low" (n=469) recurrence risk groups and randomised to flexible sigmoidoscopy or colonoscopy at varying intervals. Only 81 recurrent adenomas (30/81 were >1 cm in diameter) were detected in the 2307 person years of follow up within the surveillance study. Adenoma recurrence was significantly higher in the high risk group (relative rate 1.82; 95% confidence interval 1.2-2.9) but recurrence rates per 1000 person years were low and not significantly different in those surveyed by colonoscopy or flexible sigmoidoscopy. Loss to follow up was greatest in those having an annual examination compared with two or five yearly surveillance examinations. Despite surveillance, invasive cancer developed in four patients compared with an expected value of 9.12 for the general population in England (p=0.10); of these four patients who developed cancers, only one was detected by surveillance examination., Conclusions: Adenoma recurrence rates were much lower than expected in both high and low risk groups. This suggests that endoscopic surveillance should be targeted at high risk groups. A surveillance interval of five years was as effective as shorter intervals in terms of cancer prevention, and was associated with similar compliance to two yearly examinations.

Most case-control studies of colorectal cancer have shown a positive association with energy intake. In contrast studies which have considered physical activity have found the most active to have a lower risk of colonic cancer and obesity appears to be no more than weakly related to colorectal cancer. We therefore compared energy intake determined by a diet history interview, self-reported height and weight, together with measures of lifetime job activity levels and leisure activity in the year prior to interview in 147 cases with colorectal adenomas and two control groups (a) 153 age-sex matched FOB-negative subjects (b) 176 FOB-positive subjects in whom no adenoma or carcinoma was found. Unconditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals () adjusted for age, sex and social class. No association with weight or body mass index was found. The only association with physical activity found with both control groups was an inverse association with running or cycling for half an hour continuously at least once a week RR 0.46 (0.2-1.3) compared with control group (a), and RR = 0.32 (0.1-0.8) compared with (b), but few subjects engaged in such activity. There was an inverse association with energy intake (trend chi 2 = 5.3, P < 0.025) in the comparison with control group (a) only, a finding which is consistent with those of two previous studies of asymptomatic adenoma.

Diets high in animal fat and protein and low in fibre and calcium are thought to be factors in the etiology of colorectal cancer. Intakes of these nutrients were determined in three groups participating in a randomised trial of faecal occult blood (FOB) screening. A diet history was obtained by interview from 147 patients with colorectal adenomas, 153 age and sex matched FOB-negative controls (a) and 176 FOB-positive controls without colorectal neoplasia (b). Unconditional logistic regression was used to estimate relative risks (RR) and 95% confidence limits (increases) adjusted for age, sex and social class. After adjustment for total energy intake, no associations were found with total, saturated or mono-unsaturated fat, or calcium intake. For total fibre intake there were non-linear relationships with both control groups with the crude RR for highest quintiles of total fibre intake compared to the lowest being 0.6, although this pattern was no longer apparent after adjustment for energy intake with group (a). In comparison with group (b) cereal fibre intake showed a more consistent inverse relationship with adenoma prevalence with the RR for ascending quintiles of intake being 1.0, 0.7 (0.3-1.6), 0.5 (0.3-1.1), 0.7 (0.4-1.4) and 0.3 (0.1-0.6) (trend chi 2 = 8.80, p = 0.003). In comparison with group (a), the adjusted RR for the highest quintile of cereal fibre intake compared with the lowest was 0.6, but no clear trend was apparent. There was an unexpected positive relationship between adenomas and polyunsaturated fat intake with the RR for having an adenoma being 1.0, 2.8 (1.3-6.1), 1.6 (0.7-3.4), 3.5 (1.6-7.5) and 2.3 (1.1-5.0) for ascending quintiles of polyunsaturated fat intakes (trend chi 2 = 4.8, P = 0.03) in comparison with group (a) only. Our data, while providing no support for the role of dietary animal fat or protein, do support the protective role of dietary cereal fibre in the etiology of colorectal adenomas.