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Objective Evidence of reduction in colorectal cancer (CRC) mortality following CRC screening based on the faecal immunochemical test (FIT) is insufficient. This study aimed to analyse if CRC mortality was reduced after implementing FIT-based screening. Setting The Danish national CRC screening programme. Methods This nationwide cohort study included residents aged 50–71 years invited to the prevalence round of the screening programme. Invitation order was decided by randomising on birth month; the first two birth months to be invited were classified as invited and the five last were classified as not-yet-invited and given a pseudo invitation data. Follow-up was from (pseudo)invitation date until 31 December 2017, emigration or death. Relative risk (RR) of CRC death was calculated with 95% confidence intervals (CIs). Results A total of 897,812 residents were included (29% invited and 71% not-yet-invited). The median follow-up was 3.3 years. The RR of CRC death at end of follow-up was 0.83 (95% CI 0.66; 1.03) among those invited to screening compared with those not yet invited. For men aged 60–71 years, this RR was 0.68 (95% CI 0.49; 0.94). For those participating in screening compared with a similar group of not-yet-invited residents, the RR was 0.71 (95% CI 0.46–1.08). For male participants aged 60–71 years, this RR was 0.49 (95% CI 0.27−0.89). For women and men aged 50–59 years, RRs were small and statistically non-significant. Conclusion This nationwide study showed that even within a median follow-up of only 3.3 years, implementing FIT-based CRC screening reduced CRC mortality among older men.

Background: Blood-based biomarkers used for colorectal cancer screening need to be developed and validated in appropriate screening populations. We aimed to develop a cancer-associated protein biomarker test for the detection of colorectal cancer in a screening population. Methods: Participants from the Danish Colorectal Cancer Screening Program were recruited. Blood samples were collected prior to colonoscopy. The cohort was divided into training and validation sets. We present the results of model development using the training set. Age, sex, and the serological proteins CEA, hsCRP, TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, ferritin and B2M were used to develop a signature test to discriminate between participants with colorectal cancer versus all other findings at colonoscopy. Results: The training set included 4048 FIT-positive participants of whom 242 had a colorectal cancer. The final model for discriminating colorectal cancer versus all other findings at colonoscopy had an AUC of 0.70 (95% CI: 0.66–0.74) and included age, sex, CEA, hsCRP, HE4 and ferritin. Conclusion: The performance of the biomarker signature in this FIT-positive screening population did not reflect the positive performance of biomarker signatures seen in symptomatic populations. Additional biomarkers are needed if the serological biomarkers are to be used as a frontline screening test.

Introduction: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multi-country European cohort. Methods: We used baseline and follow-up questionnaire data from the EPIC cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index and physical activity collected at the two timepoints. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). Results: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. Median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI>11), those in the bottom tertile at follow-up (HLI≤9) had a higher CRC risk (HR 1.34; 95%CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95%CI 0.59-1.00) than those remaining in the bottom tertile. Discussion: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

Purpose Alcohol consumption is a major risk factor for colorectal cancer (CRC). It is currently poorly understood, however, how alcohol and different alcoholic beverage types are related to psychosocial outcomes in CRC survivors. Methods We used data of N = 910 CRC survivors from the pooled EnCoRe and PROCORE cohorts and harmonized them into five time points: at diagnosis and 3, 6, 12, and 24 months post-diagnosis. Generalized estimated equation models were used to examine longitudinal associations of alcohol consumption, including consumption of beer, wine, and liquor, with anxiety, depression, and health-related quality of life (HRQoL), while correcting for sociodemographic, lifestyle, and clinical factors. Results Survivors were on average 67 years and 37% was female. In the first 2 years post-diagnosis, survivors who consumed more alcoholic drinks/week reported lower anxiety and depressive symptoms and better HRQoL on all domains and symptom scales. This was the case for moderate and heavy amounts of alcohol and mostly for consuming beer and wine, but not for liquor. Associations were more often significant for men and for younger persons ( Conclusions Generally, alcohol consumption was observed to be longitudinally related to less anxiety and depression and better HRQoL in CRC survivors. Implications for Cancer Survivors Although alcohol consumption is generally unfavorable due to increased risk of carcinogenesis and worse prognosis after CRC, it seems to be associated with better psychosocial outcomes in the first 2 years after diagnosis and treatment. More research is needed to gain knowledge about reasons for drinking and causality.

Objective. To describe the burden of colorectal cancer (CRC) in Mexico and understand mortality patterns based on sex, geography, and insurance status. Materials and methods. Mortality data (1998-2018) from the Instituto Nacional de Estadística y Geografía was obtained. We included colon (C18.0, C18.2-18.9) and rectal cancer ICD-10 codes (C19, C20), and estimated age-standardized national, state-level and health insurance mortality rates. We estimated the average annual percent change using joinpoint regression. Results. Between 1998 and 2018, the observed women and men mortality rate increased annually by 1.3 and 2.7%, respectively. Higher CRC mortality was observed in northern and more urbanized states and in groups with greater access to health insurance, which currently facilitates but does not routinely cover screening. Conclusion. CRC mortality in Mexico is increasing rapidly, with marked differences based on sex, geography, and insurance status. Our findings underscore potential benefits of increased investment in comprehensive screening, diagnosis, and treatment strategies for the general population.

Alcohol consumption is thought to be one of the modifiable risk factors for colorectal cancer (CRC). However, the causality and mechanisms by which alcohol exerts its carcinogenic effect are unclear. We evaluated the association between alcohol consumption and CRC risk by analyzing data from 32 cohort studies and conducted two-sample Mendelian randomization (MR) analysis to examine for casual relationship. To explore the effect of alcohol related DNA methylation on CRC risk, we performed an epigenetic MR analysis with data from an epigenome-wide association study (EWAS). We additionally performed gene-alcohol interaction analysis nested in the UK Biobank to assess effect modification between alcohol consumption and susceptibility genes. We discovered distinct effects of alcohol on CRC incidence and mortality from the meta-analyses, and genetic predisposition to alcohol drinking was causally associated with an increased CRC risk (OR = 1.79, 95% CI: 1.23-2.61) using two-sample MR approaches. In epigenetic MR analysis, two alcohol-related CpG sites (cg05593667 and cg10045354 mapped to COLCA1/COLCA2 gene) were identified causally associated with an increased CRC risk (P

OBJECTIVES: We aimed to produce clinical recommendations for colonoscopic surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel diseases.MATERIALS AND METHODS: The Danish Society for Gastroenterology and Hepatology convened a committee to assess the literature on colorectal cancer in inflammatory bowel diseases and the effectiveness of colonoscopy surveillance, according to the Oxford Centre for Evidence Based Medicine levels of evidence.RESULTS: Clinical recommendations for the colonoscopic surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel diseases were produced. These guidelines cover the risk stratification, entry, and follow-up of patients in the colonoscopy programme, the choice of image-enhanced colonoscopy modality, the investigation and treatment of lesions, and the management of special patient populations in the colonoscopy programme.CONCLUSIONS: Colonoscopic surveillance of inflammatory bowel disease is thought to be associated with a decreased risk of colorectal cancer and colorectal cancer-related mortality. Further evidence regarding the effectiveness of colonoscopic surveillance will contribute to understanding its role in the management of inflammatory bowel diseases. The Danish Society for Gastroenterology and Hepatology clinical guideline will aid gastroenterologists in the risk stratification of patients with inflammatory bowel disease, and the management of colorectal lesions. Gastroenterologists must inform and support patients with inflammatory bowel disease to decide whether to participate in the colonoscopic surveillance programme.

Epigenetic clocks have been associated with cancer risk in several observational studies. Nevertheless, it is unclear whether they play a causal role in cancer risk or if they act as a non-causal biomarker.We conducted a two-sample Mendelian randomization (MR) study to examine the genetically predicted effects of epigenetic age acceleration as measured by HannumAge (nine single-nucleotide polymorphisms (SNPs)), Horvath Intrinsic Age (24 SNPs), PhenoAge (11 SNPs), and GrimAge (4 SNPs) on multiple cancers (i.e. breast, prostate, colorectal, ovarian and lung cancer). We obtained genome-wide association data for biological ageing from a meta-analysis (N = 34,710), and for cancer from the UK Biobank (N cases = 2671-13,879; N controls = 173,493-372,016), FinnGen (N cases = 719-8401; N controls = 74,685-174,006) and several international cancer genetic consortia (N cases = 11,348-122,977; N controls = 15,861-105,974). Main analyses were performed using multiplicative random effects inverse variance weighted (IVW) MR. Individual study estimates were pooled using fixed effect meta-analysis. Sensitivity analyses included MR-Egger, weighted median, weighted mode and Causal Analysis using Summary Effect Estimates (CAUSE) methods, which are robust to some of the assumptions of the IVW approach.Meta-analysed IVW MR findings suggested that higher GrimAge acceleration increased the risk of colorectal cancer (OR = 1.12 per year increase in GrimAge acceleration, 95% CI 1.04-1.20, p = 0.002). The direction of the genetically predicted effects was consistent across main and sensitivity MR analyses. Among subtypes, the genetically predicted effect of GrimAge acceleration was greater for colon cancer (IVW OR = 1.15, 95% CI 1.09-1.21, p = 0.006), than rectal cancer (IVW OR = 1.05, 95% CI 0.97-1.13, p = 0.24). Results were less consistent for associations between other epigenetic clocks and cancers.GrimAge acceleration may increase the risk of colorectal cancer. Findings for other clocks and cancers were inconsistent. Further work is required to investigate the potential mechanisms underlying the results.FMB was supported by a Wellcome Trust PhD studentship in Molecular, Genetic and Lifecourse Epidemiology (224982/Z/22/Z which is part of grant 218495/Z/19/Z). KKT was supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme) and by the Hellenic Republic's Operational Programme 'Competitiveness, EntrepreneurshipInnovation' (OΠΣ 5047228). PH was supported by Cancer Research UK (C18281/A29019). RMM was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. GDS and CLR were supported by the Medical Research Council (MC_UU_00011/1 and MC_UU_00011/5, respectively) and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). REM was supported by an Alzheimer's Society project grant (AS-PG-19b-010) and NIH grant (U01 AG-18-018, PI: Steve Horvath). RCR is a de Pass Vice Chancellor's Research Fellow at the University of Bristol.Have you noticed that some people seem to get older faster than others? Scientists have previously found that a chemical tag on DNA known as DNA methylation can be used to predict an individual’s chronological age. However, age predicted using DNA methylation (also known as biological or epigenetic age) does not always perfectly correspond to chronological age. Indeed, some people’s biological age is higher than their years, while other people’s is lower. When an individual’s biological age is higher than their chronological age, they are said to be experiencing ‘epigenetic age acceleration’. This type of accelerated ageing, which can be measured with ‘epigenetic clocks’ based on DNA methylation, has been associated with several adverse health outcomes, including cancer. This means that epigenetic clocks may improve our ability to predict cancer risk and detect cancer early. However, it is still unclear whether accelerated biological ageing causes cancer, or whether it simply correlates with the disease. Morales-Berstein et al. wanted to investigate whether epigenetic age acceleration, as measured by epigenetic clocks, plays a role in the development of several cancers. To do so, they used an approach known as Mendelian randomization. Using genetic variants as natural experiments, they studied the effect of different measures of epigenetic age acceleration on cancer risk. Their work focused on five types of cancer: breast, colorectal, prostate, ovarian and lung cancer. They used genetic association data from people of European ancestry to determine whether genetic variants that are strongly associated with accelerated ageing are also strongly associated with cancer. The results showed that one of the DNA methylation markers used as an estimate of biological ageing could be directly related to the risk of developing colorectal cancer. This work provides new insights into the relationship between markers of biological ageing and cancer. Similar relationships should also be studied in other groups of people and for other cancer sites. The results suggest that reversing biological ageing by altering DNA methylation could prevent or delay the development of colorectal cancer.

BackgroundThe risk of colorectal cancer (CRC) among subjects with a positive faecal immunochemical test (FIT) who do not undergo a colonoscopy is unknown. We estimated whether non-compliance with colonoscopy after a positive FIT is associated with increased CRC incidence and mortality.MethodsThe FIT-based CRC screening programme in the Veneto region (Italy) invited persons aged 50 to 69 years with a positive FIT (>20 µg Hb/g faeces) for diagnostic colonoscopy at an endoscopic referral centre. In this retrospective cohort study, we compared the 10-year cumulative CRC incidence and mortality among FIT positives who completed a diagnostic colonoscopy within the programme (compliers) and those who did not (non-compliers), using the Kaplan-Meier estimator and Cox-Aalen models.ResultsSome 88 013 patients who were FIT positive complied with colonoscopy (males: 56.1%; aged 50–59 years: 49.1%) while 23 410 did not (males: 54.6%; aged 50–59 years: 44.9%).The 10-year cumulative incidence of CRC was 44.7 per 1000 (95% CI, 43.1 to 46.3) among colonoscopy compliers and 54.3 per 1000 (95% CI, 49.9 to 58.7) in non-compliers, while the cumulative mortality for CRC was 6.8 per 1000 (95% CI, 5.9 to 7.6) and 16.0 per 1000 (95% CI, 13.1 to 18.9), respectively. The risk of dying of CRC among non-compliers was 103% higher than among compliers (adjusted HR, 2.03; 95% CI, 1.68 to 2.44).ConclusionThe excess risk of CRC death among those not completing colonoscopy after a positive faecal occult blood test should prompt screening programmes to adopt effective interventions to increase compliance in this high-risk population.

Objective To investigate the long-term association between four dietary quality indices and the risk of gastrointestinal (GI) cancer. Methods Baseline details of the dietary intake of participants, assessed by a single food frequency questionnaire from the prospective Lifelines population-based cohort were translated to diet quality scores using several dietary and dietary-lifestyle indices. Incident cases of GI cancer were then assessed by linkage to the Dutch nationwide histo-cytopathology registry. The association between GI cancer risk and diet quality (defined as higher quintiles on dietary indices compared to the first quintile) was assessed by multivariable Cox proportional hazard models. Results We included 72,695 participants aged 51.20 ± 8.71 years with a median follow-up to cancer diagnosis of 8 years (interquartile range 2 years). During follow-up, 434 colorectal cancers and 139 upper GI cancers were diagnosed. There was a significant reduction in colorectal cancer risk for high categories in the American Cancer Society (ACS) Index (hazard ratio 0.62; 95% CI 0.46–0.84). However, high dietary index scores were not associated with strong beneficial effects on upper GI cancer risk. Conclusion High quintiles on the ACS Index were associated with a significantly reduced risk of colorectal cancer. This index may be of use in a colorectal cancer prevention program.

Background Surgery is the main curative treatment for colorectal cancer. Yet the immunologic and humoral response to surgery may facilitate progression of micro-metastases. It has been suggested that epidural analgesia preserves immune competency and prevents metastasis formation. Hence, the authors tested the hypothesis that epidural analgesia would result in less cancer recurrence after colorectal cancer surgery. Methods The Danish Colorectal Cancer Group Database and the Danish Anesthesia Database were used to identify patients operated for colorectal cancer between 2004 and 2018 with no residual tumor tissue left after surgery. The exposure group was defined by preoperative insertion of an epidural catheter for analgesia. The primary outcome was colorectal cancer recurrence, and the secondary outcome was mortality. Recurrences were identified using a validated algorithm based on data from Danish health registries. Follow-up was until death or September 7, 2018. The authors used propensity score matching to adjust for potential preoperative confounders. Results In the study population of 11,618 individuals, 3,496 (30.1%) had an epidural catheter inserted before surgery. The epidural analgesia group had higher proportions of total IV anesthesia, laparotomies, and rectal tumors, and epidural analgesia was most frequently used between 2009 and 2012. The propensity score–matched study cohort consisted of 2,980 individuals in each group with balanced baseline covariates. Median follow-up was 58 months (interquartile range, 29 to 86). Recurrence occurred in 567 (19.0%) individuals in the epidural analgesia group and 610 (20.5%) in the group without epidural analgesia. The authors found no association between epidural analgesia and recurrence (hazard ratio, 0.91; 95% CI, 0.82 to 1.02) or mortality (hazard ratio, 1.01; 95% CI, 0.92 to 1.10). Conclusions In colorectal cancer surgery, epidural analgesia was not statistically significantly associated with less cancer recurrence. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Patients with inflammatory bowel disease are at an increased risk of cancer secondary to long-standing intestinal inflammation. Surgical options must take into account the significant risk of synchronous disease at other colonic sites. Ileal pouch anal anastomosis is a viable option for patients with ulcerative colitis, but this should be restricted to early cancers that are unlikely to require preoperative or postoperative radiation treatment.

Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Background & Aims Patients with inflammatory bowel diseases who have postinflammatory polyps (PIPs) have an increased risk of colorectal neoplasia (CRN). European guidelines propose that patients with PIPs receive more frequent surveillance colonoscopies, despite limited evidence of this increased risk. We aimed to define the risk of CRN and colectomy in patients with inflammatory bowel diseases and PIPs. Methods We conducted a multicenter retrospective cohort study of patients with inflammatory bowel diseases who underwent colonoscopic surveillance for CRN, from January 1997 through January 2017, at 5 academic hospitals and 2 large nonacademic hospitals in New York or the Netherlands. Eligible patients had confirmed colonic disease with duration of at least 8 years (or any duration, if they also had primary sclerosing cholangitis) and no history of advanced CRN (high-grade dysplasia or colorectal cancer) or colectomy. The primary outcome was occurrence of advanced CRN according to PIP status; secondary outcomes were occurrence of CRN (inclusive of low-grade dysplasia) and colectomy. Results Of 1582 eligible patients, 462 (29.2%) had PIPs. PIPs were associated with more severe inflammation (adjusted odds ratio 1.32; 95% confidence interval [CI] 1.13–1.55), greater disease extent (adjusted odds ratio 1.92; 95% CI 1.34–2.74), and lower likelihood of primary sclerosing cholangitis (adjusted odds ratio 0.38; 95% CI 0.26–0.55). During a median follow-up period of 4.8 years, the time until development of advanced CRN did not differ significantly between patients with and those without PIPs. PIPs did not independently increase the risk of advanced CRN (adjusted hazard ratio 1.17; 95% CI 0.59–2.31). The colectomy rate was significantly higher in patients with PIPs (P = .01). Conclusions In a retrospective analysis of data from 2 large independent surveillance cohorts, PIPs were associated with greater severity and extent of colon inflammation and higher rates of colectomy, but were not associated with development of any degree of CRN. Therefore, intervals for surveillance should not be shortened based solely on the presence of PIPs.

Background & Aims: Patients with inflammatory bowel diseases who have postinflammatory polyps (PIPs) have an increased risk of colorectal neoplasia (CRN). European guidelines propose that patients with PIPs receive more frequent surveillance colonoscopies, despite limited evidence of this increased risk. We aimed to define the risk of CRN and colectomy in patients with inflammatory bowel diseases and PIPs. Methods: We conducted a multicenter retrospective cohort study of patients with inflammatory bowel diseases who underwent colonoscopic surveillance for CRN, from January 1997 through January 2017, at 5 academic hospitals and 2 large nonacademic hospitals in New York or the Netherlands. Eligible patients had confirmed colonic disease with duration of at least 8 years (or any duration, if they also had primary sclerosing cholangitis) and no history of advanced CRN (high-grade dysplasia or colorectal cancer) or colectomy. The primary outcome was occurrence of advanced CRN according to PIP status; secondary outcomes were occurrence of CRN (inclusive of low-grade dysplasia) and colectomy. Results: Of 1582 eligible patients, 462 (29.2%) had PIPs. PIPs were associated with more severe inflammation (adjusted odds ratio 1.32; 95% confidence interval [CI] 1.13–1.55), greater disease extent (adjusted odds ratio 1.92; 95% CI 1.34–2.74), and lower likelihood of primary sclerosing cholangitis (adjusted odds ratio 0.38; 95% CI 0.26–0.55). During a median follow-up period of 4.8 years, the time until development of advanced CRN did not differ significantly between patients with and those without PIPs. PIPs did not independently increase the risk of advanced CRN (adjusted hazard ratio 1.17; 95% CI 0.59–2.31). The colectomy rate was significantly higher in patients with PIPs (P =.01). Conclusions: In a retrospective analysis of data from 2 large independent surveillance cohorts, PIPs were associated with greater severity and extent of colon inflammation and higher rates of colectomy, but were not associated with development of any degree of CRN. Therefore, intervals for surveillance should not be shortened based solely on the presence of PIPs.

About 10-20% of patients with metastatic colorectal cancer (mCRC) are candidates for metastasis directed therapies such as surgical resection, ablation and stereotactic radiotherapy. We examined the temporal changes in use of metastasis directed therapies and established prognostic factors for survival in a nationwide cohort study. The Danish nationwide medical registries were used to retrieve data on treatment for liver and/or lung metastasis in patients with metastatic colorectal cancer in the period 2000-2013. Overall survival through 2014 was calculated from the time of treatment of metastases by Kaplan-Meier method and mortality between groups was assessed using Cox regression. We report 2912 patients undergoing a total of 3602 procedures with an increased use of all modalities during 14 calendar years. Median survival was 3.7 years (interquartile range (IQR) 2.0-9.7 years). In the multivariate analysis the nodal stage of the primary tumor had the most pronounced association with survival with a hazard ratio for mortality of 1.56 (95% CI: 1.33-1.83) for N2 stage with reference to N0. Furthermore, female gender, age, comorbidity, surgical treatment, administration of chemotherapy and left sided primary tumors were associated with improved prognosis in the multivariate analysis. This article is protected by copyright. All rights reserved.

Objective - To systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts. Design - Models were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability). Results - The systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC. Conclusion - Several of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.

Socioeconomic inequalities in cancer stage at diagnosis and survival are important public health issues. This study investigates the association between socioeconomic position (SEP) and colorectal cancer (CRC) stage at diagnosis and survival in Switzerland, a European country with highest level of medical facilities and life expectancy. We used population‐based CRC data from seven Swiss cantonal cancer registries 2001–2008 (N = 10,088) linked to the Swiss National Cohort (SNC). Follow‐up information was available until the end of 2013. SEP was estimated based on education. The association between cancer stage and SEP was assessed using logistic regression models including cancer localization (colon/rectum), sex, age, civil status, urbanity of residence, language region, and nationality (Swiss/non‐Swiss). Survival was analyzed using competing risk regressions reporting subhazard ratios (SHRs) for the risk of dying due to CRC. We observed a social gradient for later stage CRC with adjusted odds ratios (ORs) of 1.11 (95% CI: 0.97–1.19) and 1.28 (95% CI: 1.08–1.50) for middle and low SEP compared to high SEP. Further, single compared to married people had elevated odds of being diagnosed at later stages. Survival was lower in patients with CRC with low SEP in the unadjusted model (SHR: 1.18, 95% CI: 1.07–1.30). After adjustment for stage at diagnosis and further sociodemographic characteristics, significant survival inequalities by SEP disappeared but remained for non‐Swiss compared to Swiss citizens and for patients living in nonurban areas compared to their urban counterparts. Swiss public health strategies should facilitate equal access to CRC screening and optimal CRC care for all social groups and in all regions of Switzerland.

Background: The overall risk of cancer following ileal pouch-anal anastomosis [IPAA] is unknown, and pouch cancer surveillance is controversial. We evaluated long-term risk of cancer in a national cohort of patients with ulcerative colitis and IPAA, with emphasis on pouch cancer.Methods: Data on incident cancers were extracted from the national Danish Cancer Registry. Incidence rates for all site-specific cancers were compared between patients with IPAA and a gender- and age-matched comparison cohort from the background population to obtain incidence rate ratios [IRRs].Results: A total of 1723 patients with IPAA, operated for ulcerative colitis in the period 1980-2010, were matched to 8615 individuals from the background population. During a median follow-up of 12.9 years (interquartile range [IQR] 7.7-19.6 years), two pouch cancers [0.12%] were found after 16 and 27 years, respectively. In the population comparison cohort, 38 intestinal cancers [0.45%] were found, of which 35 were colorectal. The risk of hepatobiliary cancer was higher for patients with IPAA {IRR = 13.0 (95% confidence interval [CI]: 3.1-76.1)}, and half of the affected patients had coexisting primary sclerosing cholangitis. The risk of cancer overall following IPAA was identical to that of the comparison cohort: IRR = 1.05 [0.84-1.31].Conclusions: Pouch cancer following IPAA is very rare, questioning the need for general, rather than selective, surveillance. The overall cancer risk is comparable to that of the background population, and the increased risk of hepatobiliary cancer is likely an effect of coexisting liver disease and not causally related to IPAA.

INTRODUCTION: Colorectal cancer is the third most common type of cancer worldwide. Recurrence is an important end-point in colorectal cancer research. This study aimed to validate a previously developed algorithm to determine recurrence after surgery for rectal cancer.METHODS: Information about a cohort of 500 patients with rectal cancer was retrieved from the Danish Civil Registration System, the Danish National Patient Register and the Danish National Pathology Register. Patients with an ICD-10 code for metastatic disease, chemotherapy or SNOMED code suggesting metastasis were identified as having recurrence. In a previous study, medical records of the same cohort had been reviewed to identify recurrence. Recurrence identified by the algorithm was compared with the previously retrieved information from the medical records using Kappa statistics. The sensitivity and specificity of the algorithm were determined.RESULTS: Of the 500 patients, 393 were included in the validation analysis. Kappa statistics showed good concordance with a Kappa value (95% confidence interval) of 0.80 (0.72-0.88). The sensitivity and specificity of the algorithm were 88% (77-95%) and 96% (93-98%), respectively.CONCLUSIONS: The study showed good concordance between the algorithm and medical record information. The algorithm makes it possible to perform large register-based studies of recurrence and disease-free survival in colorectal cancer patients without the need for evaluation of medical records.FUNDING: none.TRIAL REGISTRATION: not relevant.

Contains fulltext : 177780.pdf (Publisher’s version ) (Open Access) BACKGROUND: Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens. METHODS: In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses. RESULTS: After a median follow-up of 22.9 years, 55 patients developed CRC. The standardized incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95%CI) 1.8-3.2), leading to 5.7 excess cases per 10 000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95%CI: 1.6-4.6). The highest (SIR: 6.5, 95%CI: 3.3-11.3) was seen for transverse colon cancer (15.0 (95%CI: 4.3-40.8) after inverted-Y irradiation). A prescribed cumulative procarbazine dose >4.2 g m-2 was associated with a 3.3-fold higher CRC risk (95%CI: 1.8-6.1) compared to treatment without procarbazine. Patients receiving >4.2 g m-2 procarbazine and infradiaphragmatic radiotherapy had a hazard ratio of 6.8 (95%CI: 3.0-15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (Padditivity=0.004). CONCLUSIONS: Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.

Supplemental Digital Content is Available in the Text., Background: As people with HIV live longer, the numbers of colorectal cancer cases are expected to increase. We sought to compare the colorectal cancer incidence and cause-specific mortality among people living with and without HIV. Design: Systematic review and meta-analysis. Methods: We searched 5 electronic databases up to June 28, 2016, for primary studies reporting standardized incidence ratios (SIRs), standardized mortality ratios (SMRs)/hazard ratios or data sufficient for estimating these summary measures. We performed a random effects pooled analysis to estimate SIR and SMR of colorectal cancer in HIV. Results: Of 8110 articles, we included 27 studies from North America (n = 18), Europe (n = 7), the Pacific region (n = 4), and South America (n = 1). Overall, 1660 cases of colorectal cancer and colon cancer (excluding rectal cancer) occurred among 1,696,070 persons with HIV. In pooled analysis, we found no summary risk of malignancy among those with HIV relative to an uninfected population (SIR 1.00; 95% confidence interval 0.82 to 1.22; I2 = 89.2%). Colorectal cancer–specific mortality was higher among people with HIV but did not reach statistical significance (SMR 2.09; 95% confidence interval: 1.00 to 4.40; I2 = 85.0%). Conclusions: Rates of colorectal cancer are similar between people with and without HIV. Existing screening guidelines are likely adequate for people with HIV.

In vitro and animal studies indicate that metformin prevents colorectal cancer (CRC). Epidemiological studies, however, have been equivocal. We undertook this study to assess whether metformin prevents CRC in individuals with type II diabetes. We performed a nested case-control study restricted to Danish citizens with type II diabetes. Data were collected from four Danish nationwide registries. Cases were type II diabetics with a primary CRC between 2000 and 2009, and controls were sampled among subjects with type II diabetes. Long-term exposure to metformin was defined by the redeeming of prescriptions for a cumulative dose of 2000 g within 5 years prior to the index date. To control for potential confounders, we used unconditional logistic regression. We generated adjusted odds ratios (OR) for the association between metformin and CRC and performed subanalyses for selected subgroups and for the dose-response relation. We identified 2088 cases and 9060 controls during the study period. The association between long-term metformin use and CRC gave an adjusted OR at 0.83 (95% CI 0.68-1.00). A protective effect on CRC with long-term use of metformin was only evident for women (OR 0.66 vs. 0.99 for men). There was a significant dose-response association of metformin use >250 defined daily dose (DDD) and for the duration of metformin use >1 year. We found an indication of a protective effect of long-term metformin use against CRC in type II diabetics, although this effect was only seen in women. We performed a nested case-control study restricted to Danish citizens with type II diabetes. The association between long-term metformin use and colorectal cancer (CRC) gave an adjusted odds ratios at 0.83 (95 % CI 0.68-1.00). A protective effect on CRC with long-term use of metformin was only evident for women (OR 0.66 vs. 0.99 for men). There was a significant dose-response association of metformin use >250 defined daily dose (DDD) and for the duration of metformin use >1 year.

OBJECTIVE: To systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts. DESIGN: Models were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability). RESULTS: The systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC. CONCLUSION: Several of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.

Background Little is known about the use of complementary and alternative medicine (CAM) for colorectal cancer, despite the high incidence of colorectal cancer and the frequency of CAM use for cancer-related symptoms. This is the first Danish study to examine the use of CAM by individuals who completed hospital treatment for colorectal cancer. Methods In 2011–12, a pragmatic trial on energy healing as rehabilitation after colorectal cancer was conducted in Denmark with participants who had completed cancer-related hospital treatment within the past 18 months prior to study inclusion. As part of the trial, participants (n = 247) completed a questionnaire on the use, motivations, pathways and perceived benefits of CAM. Socio-demographic information was obtained via the Danish National Patient Registry and self-report. Descriptive statistics were generated, using SPSS, version 18, and logistic regression analysis was carried out. Results Of 247 individuals, 49.4% used some form of CAM in the past month. Nearly half of the CAM users (49.2%) used natural medicines and/or dietary supplements only; 32% consulted an alternative therapist; 18.9% used both. Those who consulted alternative therapists were most commonly women (OR: 3.36; p = .002; CI: 1.54-7.33) with high educational levels (OR: 2.77; p = 0.010; CI: 1.28-6.01); more women than men used natural medicines and/or dietary supplements (OR: 1.83; p = .047; CI: 1.01-3.30) independent of educational levels. A majority commenced CAM on their own initiative; CAM was predominantly used to achieve better physical wellbeing. Beneficial effects were reported particularly in relation to physical health; few harmful effects were reported. Of those using CAM, 51.5% did not disclose its use to their physician; 8.5% of participants reported to have been asked by their physician about CAM use. Conclusion The use of CAM following completion of hospital treatment for colorectal cancer seems widespread in Denmark. The identified extensive CAM use suggests a need for more reliable and diverse information about CAM for both patients and biomedical providers, and improved communication about its use in the clinical context. Electronic supplementary material The online version of this article (doi:10.1186/1472-6882-14-388) contains supplementary material, which is available to authorized users.

Introduction: Colorectal carcinoma is hardly found in individuals below 50 years of age, and there are still controversies regarding its behavior and prognosis. Objective: To evaluate the epidemiological, clinical, histopathological and treatment of patients with colorectal carcinoma, comparing the age groups up to 50 years and older than 50 years. Method: This is a descriptive study, which examined records of 505 patients with colorectal carcinoma, treated from January 1998 to December 2008. Clinical and pathological parameters were collected. Results: Individuals aged 50 years or less accounted for 26.53% of the sample and there was no gender predilection. Change in bowel habits such as initial complaint to the physical examination and anemia were significantly more common in the younger group. Patients aged 50 years or younger also showed more advanced lymph nodes staging, higher incidence of squamous cell or neuroendocrine carcinoma and worse histopathological differentiation, as well as increased local recurrence, despite a higher rate of surgical treatment and chemotherapy. Conclusion: The colorectal carcinomas in younger patients were more aggressive and undifferentiated. The complaints, even from young patients, should be promptly investigated to enable early diagnosis and a higher chance of cure for patients with colorectal carcinoma. Introducción: El cáncer colorrectal suele ser poco frecuente en personas menores de 50 años, aún existen controversias em cuanto a su comportamiento y el pronóstico. Objetivo: Evaluar los aspectos epidemiológicos, clínicos, histopatológicos y tratamiento de pacientes con cáncer colorrectal, en la comparación de los grupos de edad hasta 50 años y mayores de 50 años. Método: Se realizó un estudio descriptivo, que han sido examinados los registros hospitalarios de 505 pacientes con cáncer colorrectal, tratados entre enero de 1998 a diciembre 2008. Parámetros clínicos y histopatológicos han sido recogidos. Resultados: Las personas con edad hasta 50 años representaban el 26,53% de la muestra y no hubo predilección por el género. Cambio en los hábitos intestinales, como queja inicial de la exploración física y la anemia han sido significativamente más frecuentes en el grupo más joven. Los pacientes de hasta 50 años también han exhibido estadiamiento linfonodo más avanzado, mayor incidencia de carcinoma de espinocelular o neuroendrocino y peor diferenciación histopatológica, así como la mayor recurrencia local, a pesar de una mayor tasa de tratamiento quirúrgico y quimioterapia. Conclusión: El cáncer colorrectal en pacientes con edad hasta 50 años se ha mostrado más agresivo y no diferenciado. Las quejas, incluso de los pacientes jóvenes, deben ser investigadas con prontitud a fin de posibilitar un diagnóstico precoz y una mayor posibilidad de curación para los pacientes con cáncer colorrectal. Introdução: O câncer colorretal costuma ser pouco frequente em indivíduos abaixo dos 50 anos, persistindo ainda controvérsias quanto ao seu comportamento e prognóstico. Objetivo: Avaliar as características epidemiológicas, clínicas, histopatológicas e terapêuticas de pacientes com câncer colorretal, comparando os grupos de faixa etária até 50 anos e idade superior a 50 anos. Método: Trata-se de um estudo descritivo, em que foram analisados prontuários de 505 pacientes com câncer colorretal, atendidos de janeiro de 1998 a dezembro de 2008. Parâmetros clínicos e histopatológicos foram coletados. Resultados: Os indivíduos com idade ate 50 anos corresponderam a 26,53% da amostra e não houve predileção por gênero. Alteração no hábito intestinal como queixa inicial e anemia ao exame físico foram significativamente mais comuns no grupo mais jovem. Os pacientes ate 50 anos exibiram também estadiamento linfonodal mais avançado, maior ocorrência de carcinoma espinocelular ou neuroendócrino e pior diferenciação histopatologia, bem como maior recorrencial local, apesar de maior índice de tratamento cirúrgico e quimioterápico. Conclusão: O câncer colorretal em pacientes com idade ate 50 anos mostrou-se mais agressivo e indiferenciado. As queixas, mesmo dos pacientes jovens, devem ser prontamente investigadas, a fim de possibilitar o diagnóstico precoce e maior chance de cura ao paciente com câncer colorretal. &nbsp

INTRODUÇÃO: O estudo das vias moleculares e das alterações específicas responsáveis pela progressão desfavorável de pacientes com CCR parece essencial para o desenvolvimento de terapias mais efetivas. OBJETIVO: Comparar a expressão quantitativa dos genes TACSTD2, Ku70, KRAS mutante e SERIN1 em amostras de tecidos normal e tumoral de pacientes com CCR e relacionar sua expressão com variáveis clínico-patológicas. MÉTODOS: Foram estudados 37 pacientes com CCR submetidos à ressecção cirúrgica entre julho de 2005 e julho de 2009 e cujas amostras congeladas de tecidos tumoral e normal foram armazenadas em um banco de tecidos. Através da RT-PCR foi sintetizado o cDNA a partir do RNA extraído das amostras teciduais. A expressão dos genes TACSTD2, KRAS mutante, Ku70 e SERIN1 foi quantificada pela técnica de PCR em tempo real. RESULTADOS: A expressão do KRAS mutante foi maior no tecido tumoral do que no normal (p = 0,024). A expressão tumoral dos genes Ku70, TACSTD2 e SERIN1 foi respectivamente menor, igual e maior que o tecido normal, porém sem significância estatística. Associação estatisticamente significativa também foi observada entre idade e expressão de KRAS mutante no tecido normal e tumores pouco diferenciados e expressão de Ku70 no tecido normal. Não foram observadas outras associações estatisticamente significativas. CONCLUSÕES: A expressão do KRAS mutante no tecido tumoral é maior do que no tecido normal (p = 0,024) na casuística de 37 pacientes com CCR estudados através da técnica de PCR em tempo real. INTRODUCTION: Knowledge of the molecular pathways and of the specific alterations responsible for the unfavorable progression of patients with CCR appears essential for the development of more effective therapies. PURPOSE: To compare the quantitative expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 in samples of normal and tumoral tissues of patients with CCR and to relate their expression to clinicopathologic characteristics. METHODS: 37 patients with CCR were studied. The patients had been operated on between July 2005 and July 2009, and their frozen samples of tumoral and normal tissues had been stored in a tissue bank. The expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 was quantified through the technique of real time polymerase chain reaction. RESULTS: The mutant KRAS expression was higher in the tumoral tissue than in the normal tissue (p = 0,024). Although not significant, the tumoral expression of the genes Ku70, TACSTD2 and SERIN1 was respectively lower, equal to, and higher than in the normal tissue. Statistically significant association was also observed between age and mutant KRAS expression in normal tissue and between poorly-differentiated tumors and Ku70 expression in normal tissue. No other statistically significant associations were observed. CONCLUSIONS: Tumoral tissues express mutant KRAS at higher levels than normal tissues in the casuistic of 37 patients with CCR studied through the technique of PCR real time.

Le cancer colorectal atteint, chaque année, plus d'un million de personnes dans le monde et plus de 500'000 en meurent [1]. Il affecte de manière très inégalitaire les différentes parties du monde. En effet, s'il constitue un problème de santé publique majeur dans des régions telles que l'Amérique du Nord, l'Europe ou l'Océanie (incidence supérieure à 50 pour 100'000), il est nettement plus rare dans certains pays d'Asie, d'Afrique ou d'Amérique du Sud (incidence inférieure à 10 pour 100'000) [2]. Aux Etats-Unis, on estime que 5 à 6% de la population générale présentera un cancer colorectal au cours de sa vie [3]. En Suisse, le cancer colorectal est le deuxième cancer le plus mortel, avec quelque 1'600 décès par an, après le cancer du poumon [4]. Avec 4'000 nouveaux cas annuels, il représente 11% de tous les cancers chez l'homme et chez la femme [5]. Le cancer colorectal est le troisième cancer le plus fréquent après celui du poumon et de la prostate chez l'homme, alors qu'il n'est précédé chez la femme que par le cancer du sein. Pour la période 2003-07, l'incidence en Suisse est estimée à 50 cas/100'000 hommes et 32 cas/100'000 femmes (taux standardisés selon la population européenne) [5] et son taux de survie relative à 5 ans est de 60%, ce qui en fait le taux le plus élevé d'Europe [6]. Le fait que l'incidence chez les migrants ait tendance à rattraper celle des indigènes en moins d'une génération suggère que les facteurs environnementaux jouent un rôle prédominant dans la carcinogénèse des tumeurs colorectales [7]. Cependant, d'autres facteurs, notamment génétiques, interviennent dans la survenue des cancers colorectaux. En effet, dans des conditions de vie similaires, on observe une incidence de cancers colorectaux différente entre différentes ethnies. Des études américaines ont par exemple montré une incidence plus élevée chez les noirs (48 pour 100'000) que chez les blancs (40/100'000) ou les hispaniques (26/100'000) [8]. Les hommes sont plus fréquemment touchés par le cancer colorectal que les femmes, avec un sexe ratio de 1,5 [9]. Les premiers cas de cancers colorectaux apparaissent à partir de 25 ans et l'incidence augmente de manière quasi exponentielle jusqu'à un âge de 75-80 ans, puis se stabilise [10]. L'âge moyen au diagnostic se situe entre 65 et 70 ans. Environ 66% des cancers colorectaux sont localisés dans le côlon (dans l'ordre décroissant: au niveau du sigmoïde, du côlon ascendant, descendant et transverse), 27% dans le rectum, 4% dans l'anus tandis qu'environ 4% restent multiples et indéfinis [10]. Notons encore, qu'à des fins de comparaisons épidémiologiques, les cancers du côlon, du rectum et de l'anus sont souvent regroupés dans l'unique groupe des tumeurs colorectales.

A clear relationship between diabetes and cancer has been demonstrated. An increased incidence of several cancers is observed in diabetic patients, notably pancreatic, hepatic, colo-rectal, breast, urinary tract and endometrial cancer. By contrast a decreased incidence of prostate cancer is observed in diabetes patients implying a protective effect. Multiple potential mechanisms have been proposed but they remain hypothetical.

There is a high prevalence of depression after cancer treatment. In the literature, several authors have raised questions about assessing somatic symptoms to explore depression after cancer treatment. These somatic sequelae are a consequence of cancer treatment and should cause higher depression rates in cancer patients. In this study, the Somatic domain on a depression questionnaire, the Center for Epidemiologic Studies-Depression scale (CES-D) was analyzed in different cancer patients after treatment, as compared with a control group. Data from 566 cancer patients (oral/oropharyngeal, gynecological, colorectal, and breast cancer) and 255 randomly chosen comparison patients were analyzed. The total score on the CES-D domain of Somatic Retarded Activity significantly differed between the cancer and comparison groups; but the cancer groups showed both less somatic morbidity (colorectal cancer) and more somatic morbidity (oral/oropharyngeal, breast) than the comparison group. In the analyses of the CES-D with and without the Somatic domain, the prevalence of depression symptoms with the Somatic domain is lower for the cancer groups. Authors conclude that cancer patients are not a homogenous group as regards somatic sequelae. Evidence for removing Somatic items from the CES-D for patients after cancer treatment was not confirmed.