Colorectal Cancer-specific Mortality Research Articles

Post-diagnosis adiposity and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

The adiposity influence on colorectal cancer prognosis remains poorly characterised. We performed a systematic review and meta-analysis on post-diagnosis adiposity measures (body mass index [BMI], waist circumference, waist-to-hip ratio, weight) or their changes and colorectal cancer outcomes. PubMed and Embase were searched through 28 February 2022. Random-effects meta-analyses were conducted when at least three studies had sufficient information. The quality of evidence was interpreted and graded by the Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel. We reviewed 124 observational studies (85 publications). Meta-analyses were possible for BMI and all-cause mortality, colorectal cancer-specific mortality, and cancer recurrence/disease-free survival. Non-linear meta-analysis indicated a reverse J-shaped association between BMI and colorectal cancer outcomes (nadir at BMI 28 kg/m2). The highest risk, relative to the nadir, was observed at both ends of the BMI distribution (18 and 38 kg/m2), namely 60% and 23% higher risk for all-cause mortality; 95% and 26% for colorectal cancer-specific mortality; and 37% and 24% for cancer recurrence/disease-free survival, respectively. The higher risk with low BMI was attenuated in secondary analyses of RCTs (compared to cohort studies), among studies with longer follow-up, and in women suggesting potential methodological limitations and/or altered physiological state. Descriptively synthesised studies on other adiposity-outcome associations of interest were limited in number and methodological quality. All the associations were graded as limited (likelihood of causality: no conclusion) due to potential methodological limitations (reverse causation, confounding, selection bias). Additional well-designed observational studies and interventional trials are needed to provide further clarification.

Post-diagnosis dietary factors, supplement use and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post-diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random-effects dose-response meta-analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all-cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease-free events). Meta-analyses, including 3-10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega-3 polyunsaturated fatty acids, supplemental calcium, circulating 25-hydroxyvitamin D (25[OH]D) and all-cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer-specific mortality; and for circulating 25(OH)D and recurrence/disease-free survival. The overall evidence was graded as 'limited'. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), whole grains, total, caffeinated, or decaffeinated coffee and all-cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all-cause mortality provided 'limited-suggestive' evidence. All other exposure-outcome associations provided 'limited-no conclusion' evidence. Additional, well-conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors.

Robust best linear weighted estimator with missing covariates in survival analysis.

Missing data in covariates can result in biased estimates and loss of power to detect associations. We consider Cox regression in which some covariates are subject to missing. The inverse probability weighted approach is often applied to regression analysis with missing covariates. Inverse probability weighted estimators typically are less efficient than likelihood-based estimators, but in general are more robust against model misspecification. In this article, we propose a robust best linear weighted estimator for Cox regression with missing covariates. Our proposed estimator is the projection of the simple inverse probability weighted estimator onto the orthogonal complement of the score space based on a working regression model of the observed data. The efficiency gain is from the use of the association between the survival outcome variable and the available covariates, which is the working regression model. The asymptotic distribution is derived, and the finite sample performance of the proposed estimator is examined via extensive simulation studies. The methods are applied to a colorectal cancer study to assess the association of the microsatellite instability status with colorectal cancer-specific mortality.

Variation in colorectal cancer treatment and outcomes in Scotland: real world evidence from national linked administrative health data.

Colorectal cancer (CRC) is the fourth most common type of cancer in the United Kingdom and the second leading cause of cancer death. Despite improvements in CRC survival over time, Scotland lags behind its UK and European counterparts. In this study, we carry out an exploratory analysis which aims to provide contemporary, population level evidence on CRC treatment and survival in Scotland. We conducted a retrospective population-based analysis of adults with incident CRC registered on the Scottish Cancer Registry (Scottish Morbidity Record 06 (SMR06)) between January 2006 and December 2018. The CRC cohort was linked to hospital inpatient (SMR01) and National Records of Scotland (NRS) deaths records allowing a description of their demographic, diagnostic and treatment characteristics. Cox proportional hazards regression models were used to explore the demographic and clinical factors associated with all-cause mortality and CRC specific mortality after adjusting for patient and tumour characteristics among people identified as early-stage and treated with surgery. Overall, 32,691 (73%) and 12,184 (27%) patients had a diagnosis of colon and rectal cancer respectively, of whom 55% and 53% were early-stage and treated with surgery. Five year overall survival (CRC specific survival) within this cohort was 72% (82%) and 76% (84%) for patients with colon and rectal cancer respectively. Cox proportional hazards models revealed significant variation in mortality by sex, area-based deprivation and geographic location. In a Scottish population of patients with early-stage CRC treated with surgery, there was significant variation in risk of death, even after accounting for clinical factors and patient characteristics.

Prediagnosis ultra-processed food consumption and prognosis of patients with colorectal, lung, prostate, or breast cancer: a large prospective multicenter study.

Whether ultra-processed food consumption is associated with cancer prognosis remains unknown. We aimed to test whether prediagnosis ultra-processed food consumption is positively associated with all-cause and cancer-specific mortality in patients with colorectal, lung, prostate, or breast cancer. This study included 1,100 colorectal cancer patients, 1750 lung cancer patients, 4,336 prostate cancer patients, and 2,443 breast cancer patients. Ultra-processed foods were assessed using the NOVA classification before the diagnosis of the first cancer. Multivariable Cox regression was used to calculate hazard ratio (HR) and 95% confidence interval (CI) for all-cause and cancer-specific mortality. High ultra-processed food consumption before cancer diagnosis was significantly associated with an increased risk of all-cause mortality in lung (HRquartile 4 vs. 1: 1.18; 95% CI: 0.98, 1.40; Ptrend = 0.021) and prostate (HRquartile 4 vs. 1: 1.18; 95% CI: 1.00, 1.39; Ptrend = 0.017) cancer patients in a nonlinear dose-response manner (all Pnonlinearity < 0.05), whereas no significant results were found for other associations of interest. Subgroup analyses additionally revealed a significantly positive association with colorectal cancer-specific mortality among colorectal cancer patients in stages I and II but not among those in stages III and IV (Pinteraction = 0.006), and with prostate cancer-specific mortality among prostate cancer patients with body mass index <25 but not among those with body mass index ≥25 (Pinteraction = 0.001). Our study suggests that reducing ultra-processed food consumption before cancer diagnosis may improve the overall survival of patients with lung or prostate cancer, and the cancer-specific survival of certain subgroups of patients with colorectal or prostate cancer.

Prediagnostic 25-Hydroxyvitamin D in Association with Cancer-specific and All-cause Mortality among Low-income, Non-Hispanic Black Americans with Colorectal Cancer.

Observational studies show high prediagnosis 25-hydroxyvitamin D is associated with lower mortality after colorectal cancer diagnosis. Results from clinical trials suggest vitamin D supplementation may improve outcomes among patients with colorectal cancer. Most studies included few Black Americans, who typically have lower 25-hydroxyvitamin D. We evaluated associations between serum 25-hydroxyvitamin D and mortality after colorectal cancer diagnosis among Black American cases. Data arose from 218 Black Americans from the Southern Community Cohort Study diagnosed with colorectal cancer during follow-up (age 40-79 at enrollment). Prediagnostic 25-hydroxyvitamin D was measured at enrollment and categorized as deficient (<12 ng/mL), insufficient (12-19.9 ng/mL), or sufficient (≥20 ng/mL). Mortality was determined from the National Death Index. Cox proportional hazards were used to estimate HRs and 95% confidence intervals (CI) for associations between 25-hydroxyvitamin D and mortality. As a continuous exposure, higher 25-hydroxyvitamin D was associated with overall mortality [HR = 0.79 (0.65-0.96) per-SD increase, Ptrend = 0.02] and colorectal cancer-specific mortality [HR = 0.83 (0.64-1.08), Ptrend = 0.16]. For overall mortality, associations were strongest among females [HR = 0.65 (0.42-0.92)], current smokers [HR = 0.61 (0.38-0.98)], and obese participants [HR = 0.47 (0.29-0.77)]. Compared with those with deficiency, participants with sufficient 25-hydroxyvitamin D had lower overall mortality after multivariable adjustment [HR: 0.61 (0.37-1.01)]. Prediagnosis 25-hydroxyvitamin D is inversely associated with overall and colorectal cancer-specific mortality among Black Americans with colorectal cancer. Correcting vitamin D deficiency may improve survival of these patients, particularly for obese individuals and smokers. Our results support including more Black Americans in trials of vitamin D supplementations to improve colorectal cancer outcomes.

Mortality risk according to smoking trajectories after cancer diagnosis among Korean male cancer survivors: A population-based cohort study.

Previous research on post-diagnosis smoking among cancer survivors mainly relied on smoking status, which may not fully reflect the impact of changes in smoking levels. This study aimed to evaluate mortality risk according to smoking trajectories among Korean male cancer survivors, using a trajectory approach to comprehensively capture smoking patterns. The study included 110555 men diagnosed with cancer between 2002 and 2018 from the Korean National Health Information Database. Group-based trajectory modelling was used to identify post-diagnosis smoking trajectories among pre-diagnosis current smokers (n=45331). Cox hazards models were fitted to evaluate mortality risk according to smoking trajectories for pooled cancers, pooled smoking-related cancers, smoking-unrelated cancers, and gastric, colorectal, liver, and lung cancers. Smoking trajectories included light-smoking quitters, heavy-smoking quitters, consistent moderate smokers, and decreasing heavy smokers. Smoking significantly increased all-cause and cancer mortality risks in cancer patients for pooled cancers, pooled smoking-related cancers, and pooled smoking-unrelated cancers. Compared to non-smokers, all-cause mortality risk for pooled cancers significantly increased according to smoking trajectories:(AHR=1.33; 95% CI: 1.27-1.40), (AHR=1.39; 95% CI: 1.34-1.44), (AHR=1.44; 95% CI: 1.34-1.54), and (AHR=1.47; 95% CI: 1.36-1.60), respectively. Smoking increased all-cause and cancer mortality risks in gastric and colorectal cancer patients and cancer-specific mortality in lung cancer patients. The significant associations of smoking trajectories with all-cause and cancer mortality risks were primarily observed in 5-year survivors but not in short-term survivors. Among heavy smokers, smoking cessation significantly reduced all-cause mortality risk in the long-term. The post-diagnosis smoking trajectory independently predicts cancer prognosis among male cancer patients. Proactive cessation support should be strengthened, particularly for those who smoke heavily.

Effectiveness of Colorectal Cancer (CRC) Screening on All-Cause and CRC-Specific Mortality Reduction: A Systematic Review and Meta-Analysis.

(1) Background: The aim of this study was to pool and compare all-cause and colorectal cancer (CRC) specific mortality reduction of CRC screening in randomized control trials (RCTs) and simulation models, and to determine factors that influence screening effectiveness. (2) Methods: PubMed, Embase, Web of Science and Cochrane library were searched for eligible studies. Multi-use simulation models or RCTs that compared the mortality of CRC screening with no screening in general population were included. CRC-specific and all-cause mortality rate ratios and 95% confidence intervals were calculated by a bivariate random model. (3) Results: 10 RCTs and 47 model studies were retrieved. The pooled CRC-specific mortality rate ratios in RCTs were 0.88 (0.80, 0.96) and 0.76 (0.68, 0.84) for guaiac-based fecal occult blood tests (gFOBT) and single flexible sigmoidoscopy (FS) screening, respectively. For the model studies, the rate ratios were 0.45 (0.39, 0.51) for biennial fecal immunochemical tests (FIT), 0.31 (0.28, 0.34) for biennial gFOBT, 0.61 (0.53, 0.72) for single FS, 0.27 (0.21, 0.35) for 10-yearly colonoscopy, and 0.35 (0.29, 0.42) for 5-yearly FS. The CRC-specific mortality reduction of gFOBT increased with higher adherence in both studies (RCT: 0.78 (0.68, 0.89) vs. 0.92 (0.87, 0.98), model: 0.30 (0.28, 0.33) vs. 0.92 (0.51, 1.63)). Model studies showed a 0.62-1.1% all-cause mortality reduction with single FS screening. (4) Conclusions: Based on RCTs and model studies, biennial FIT/gFOBT, single and 5-yearly FS, and 10-yearly colonoscopy screening significantly reduces CRC-specific mortality. The model estimates are much higher than in RCTs, because the simulated biennial gFOBT assumes higher adherence. The effectiveness of screening increases at younger screening initiation ages and higher adherences.

Faecal haemoglobin concentration predicts all-cause mortality

BackgroundPopulation-based screening for colorectal cancer by a faecal immunochemical test (FIT) is recommended by the European Union. Detectable faecal haemoglobin can indicate colorectal neoplasia as well as other conditions. A positive FIT predicts an increased risk of death from colorectal cancer but might also predict an increased risk of all-cause mortality. MethodsA cohort of screening participants was followed using the Danish National Register of Causes of Death. Data were retrieved from the Danish Colorectal Cancer Screening Database supplemented with FIT concentrations. Colorectal cancer specific and all-cause mortality were compared between FIT concentration groups using multivariate cox proportional hazards regression models. FindingsIn 444,910 Danes invited for the screening program, 25,234 (5·7%) died during a mean follow-up of 56·5 months. Colorectal cancer caused 1120 deaths. The risk of colorectal cancer death increased with the increasing FIT concentration. The hazard ratios ranged from 2·6 to 25·9 compared to individuals with FIT concentrations <4 μg hb/g faeces. Causes other than colorectal cancer caused 24,114 deaths. The risk of all-cause death increased with the increasing FIT concentration, with the hazard ratios ranging from 1·6 to 5·3 compared to individuals with FIT concentrations <4 μg hb/g faeces. InterpretationThe risk of colorectal cancer mortality increased with the increasing FIT concentrations even for FIT concentrations considered negative in all European screening programs. The risk of all-cause mortality was also increased for individuals with detectable faecal blood. For colorectal cancer specific mortality and all-cause mortality, the risk was increased at the FIT concentrations as low as 4–9 μg hb/g faeces. FundingThe study was funded by the Odense University Hospital grants A3610 and A2359.

Prognostic role of inflammatory diets in colorectal cancer overall and in strata of tumor-infiltrating lymphocyte levels.

Certain dietary patterns can elicit systemic and intestinal inflammatory responses, which may influence adaptive anti-tumor immune responses and tumor behavior. We hypothesized that pro-inflammatory diets might be associated with higher colorectal cancer mortality and that the association might be stronger for tumors with lower immune responses. We calculated an empirical dietary inflammatory pattern (EDIP) score in 2829 patients among 3988 incident rectal and colon carcinoma cases in the Nurses' Health Study and Health Professionals Follow-up Study. Using Cox proportional hazards regression analyses, we examined the prognostic association of EDIP scores and whether it might be modified by histopathologic immune reaction (in 1192 patients with available data). Higher EDIP scores after colorectal cancer diagnosis were associated with worse survival, with multivariable-adjusted hazard ratios (HRs) for the highest versus lowest tertile of 1.41 (95% confidence interval [CI]: 1.13-1.77; Ptrend = 0.003) for 5-year colorectal cancer-specific mortality and 1.44 (95% CI, 1.19-1.74; Ptrend = 0.0004) for 5-year all-cause mortality. The association of post-diagnosis EDIP scores with 5-year colorectal cancer-specific mortality differed by degrees of tumor-infiltrating lymphocytes (TIL; Pinteraction = .002) but not by three other lymphocytic reaction patterns. The multivariable-adjusted, 5-year colorectal cancer-specific mortality HRs for the highest versus lowest EDIP tertile were 1.59 (95% CI: 1.01-2.53) in TIL-absent/low cases and 0.48 (95% CI: 0.16-1.48) in TIL-intermediate/high cases. Pro-inflammatory diets after colorectal cancer diagnosis were associated with increased mortality, particularly in patients with absent or low TIL.

Smoking and colorectal cancer survival in relation to tumor LINE-1 methylation levels: a prospective cohort study

BackgroundCarcinogens in cigarette smoke may cause aberrant epigenomic changes. The hypomethylation of long interspersed nucleotide element-1 (LINE-1) in colorectal carcinoma has been associated with genomic instability and worse clinical outcome. We hypothesized that the association between smoking behavior and colorectal cancer mortality might be stronger in tumors with lower LINE-1 methylation levels.FindingsTo test our hypothesis, we examined the interaction of tumor LINE-1 methylation levels and smoking status at diagnosis using data of 1208 cases among 4420 incident colorectal cancer cases that were ascertained in two prospective cohort studies. We conducted multivariable Cox proportional hazards regression analyses, using inverse probability weighting with covariate data of the 4420 cases to control for potential confounders and selection bias due to data availability. The prognostic association of smoking status at diagnosis differed by tumor LINE-1 methylation levels (Pinteraction = 0.050 for overall mortality and 0.017 for colorectal cancer-specific mortality; with an alpha level of 0.005). In cases with <60% LINE-1 methylation, current smoking (vs. never smoking) was associated with worse overall mortality (multivariable hazard ratio, 1.80; 95% confidence interval, 1.19–2.73). In contrast, smoking status was not associated with mortality in cases with ≥60% LINE-1 methylation.ConclusionsOur findings suggest that the association between smoking status and mortality is stronger in colorectal cancer patients with lower tumor LINE-1 methylation levels. These results warrant further investigation into an interactive role of smoking and aberrant DNA methylation in colorectal cancer progression.

The Associations of Multivitamin and Antioxidant Use With Mortality Among Women and Men Diagnosed With Colorectal Cancer.

BackgroundColorectal cancer survivors often use multivitamins and other over-the-counter dietary supplements, but evidence is limited regarding their potential associations with mortality.MethodsThis prospective analysis included women and men from the Cancer Prevention Study-II Nutrition Cohort who were cancer-free at baseline (1992 or 1993) and diagnosed with colorectal cancer through June 2015. Detailed information on multivitamin use, vitamin C supplements, and vitamin E supplements was self-reported on questionnaires at baseline, in 1997, and every 2 years thereafter. Pre- and postdiagnosis data were available for 3176 and 2006 colorectal cancer survivors, respectively, among whom 2116 (648 from colorectal cancer) and 1256 (242 from colorectal cancer) died. Multivariable-adjusted Cox proportional hazards regression models examined associations. All statistical tests were 2-sided.ResultsAmong colorectal cancer survivors, 49.7% and 58.5% reported multivitamin use before and after diagnosis, respectively (vitamin C use before and after diagnosis: 27.8% and 28.1%; vitamin E use before and after diagnosis: 27.5% and 29.4%, respectively). There were no statistically significant associations of pre- or postdiagnosis multivitamin use with all-cause, colorectal cancer-specific, or noncolorectal cancer mortality. Vitamin C was also not associated with any mortality outcomes. However, prediagnosis vitamin E use was associated with a non-statistically significant increased risk of all-cause mortality (multivariable adjusted hazard ratio = 1.08, 95% confidence intervals = 0.96 to 1.23) and all other noncolorectal cancer mortality (multivariable adjusted hazard ratio = 1.13, 95% confidence intervals = 0.97 to 1.31).ConclusionsThese results suggest that multivitamin use before or after diagnosis is not associated with mortality in colorectal cancer survivors. However, vitamin E use may be associated with increased risk of mortality and merits further investigation.

Long-Term Survival and Causes of Death After Diagnoses of Common Cancers in 3 Cohorts of US Health Professionals.

BackgroundFew studies investigated long-term overall survival and causes of death among men and women diagnosed with most commonly occurring cancers.MethodsWe estimated long-term (≥30-year) overall and cause-specific cumulative mortality for men diagnosed with prostate (n = 6873), lung and bronchus (n = 1290), colon and rectum (n = 1418), bladder (n = 1321), and melanoma (n = 2654) cancer in the Health Professionals Follow-up Study between 1986 and 2012 and women with breast (n = 18 280), lung and bronchus (n = 3963), colon and rectum (n = 3461), uterine corpus (n = 1641), and thyroid (n = 1103) cancer in the Nurses’ Health Study between 1976 and 2012 and Nurses’ Health Study II between 1989 and 2013.ResultsWe reported overall and cause-specific cumulative mortality of 30 years among men and 35 years among women. Among male cancer survivors, the 30-year cumulative cancer-specific mortality was 15.4% (95% confidence interval [CI] = 14.4% to 16.4%) for prostate, 83.5% (95% CI = 81.2% to 85.5%) for lung and bronchus, 37.0% (95% CI = 34.4% to 39.5%) for colon and rectum, 22.5% (95% CI = 20.0% to 25.0%) for urinary bladder, and 8.0% (95% CI = 6.9% to 9.1%) for melanoma. Among female cancer survivors, the 35-year cumulative cancer-specific mortality rate was 20.6% (95% CI = 19.7% to 21.6%) for breast, 83.5% (95% CI = 81.6% to 85.2%) for lung and bronchus, 39.6% (95% CI = 37.5% to 41.6%) for colon and rectum, 16.6% (95% CI = 14.7% to 18.6%) for uterine corpus, and 3.2% (95% CI = 2.1% to 4.3%) for thyroid. Except for lung cancer, most patients with common cancer were more likely to die from causes other than primary cancers. We observed 2 basic trends for cumulative cancer-specific mortality. The first is a sustained but nevertheless excess risk: Prostate or breast cancer-specific cumulative mortality continued to increase after diagnosis from 5 to 30 years or longer. The second is greatly diminished risk of index cancer-specific mortality following diagnosis 10 years or longer previously. For example, colorectal cancer–specific mortality increased by less than 4 percentage points between 10 and 30 or 35 years after diagnosis, and this finding also applied to lung, bladder, melanoma, uterine corpus, and thyroid cancer.ConclusionsExcept for lung cancer, patients diagnosed with common cancers were more likely to die from causes other than primary cancers. Patients with lung, colorectal, bladder, melanoma, uterine corpus, or thyroid cancer surviving longer than 10 years after diagnosis are unlikely to die from that disease.

Racial Disparities in Survival Outcomes of Colorectal Cancer Patients After Surgical Resection.

Introduction: Colorectal cancer is one of the most common cancers in the United States. Significant disparities exist among racial and ethnic minorities diagnosed with colorectal cancer compared to non-Hispanic Whites. However, understanding of survival outcomes following curative surgical resection in this population is limited.Objective: To evaluate the association between race and colorectal cancer-specific mortality in patients who were treated with major surgical resection of the colon. Materials and Methods: This study was a retrospective cohort analysis using the Surveillance, Epidemiology, and End Results (SEER) Program database from 2010 to 2016. The patient population consisted of adult patients (≥18 years old) diagnosed with a primary malignancy of colorectal cancer treated with major surgical resection of the colon. The main outcome measures were survival time at one and five years following diagnosis and cancer-specific death.Results: A total of 120,598 patients with primary colorectal malignancy treated with surgical resection of the colon were identified. Across all racial groups, most patients presented with moderately differentiated colorectal cancer. Non-Hispanic Blacks had the highest proportion of diffuse metastases (p<0.001). After adjusting for covariates, Hispanic respondents had the lowest one-year survival (adjusted HR: 1.26, 95%CI (1.21-1.31) and five-year survival when compared to Whites (adjusted HR: 1.13, 95%CI: 1.10-1.15). Factors associated with a shorter survival include age ≥ 70 years old, unmarried status, metastatic disease, and high-grade tumors (p<0.001). Conclusions: Racial disparities exist in the overall survival of patients with colorectal cancer who are treated with surgical resection of the colon. Hispanic patients had the highest hazard of death, followed by Non-Hispanic Asian-Pacific Islanders and Non-Hispanic Blacks, compared to Whites. While surgical resection can be curative, the quality and accessibility of post-operative care may differentiate survival outcomes among racial groups.

Irritable Bowel Syndrome and Long-Term Risk of Cancer: A Prospective Cohort Study Among 0.5 Million Adults in UK Biobank.

To investigate the prospective association of irritable bowel syndrome (IBS) with long-term risk of overall, site-specific cancer and cancer-specific mortality in general population. Participants free of inflammatory bowel disease, celiac disease, and any cancer at baseline from the UK Biobank were included, with patients with IBS as the exposure group and non-IBS patients as the reference group. The primary outcome was the incidence of overall cancer and cancer-specific mortality. Secondary outcomes included site-specific cancers and types of digestive cancers. The Cox proportional hazard model was used to investigate the associated risk of incident malignancies and related mortality. Among 449,595 participants, 22,338 (5.0%) were diagnosed with IBS. During a median of 12.2-year follow-up, 2,937 cases of incident cancer were identified in patients with IBS (11.47 per 1,000 person-years), compared with 60,556 cases in reference individuals (12.51 per 1,000 person-years). Of these cases, 512 and 12,282 cancer-specific deaths occurred in IBS and non-IBS groups. Compared with non-IBS, the adjusted hazard ratio for overall cancer and cancer-specific mortality was 0.97 (95% confidence interval: 0.93-1.00, P = 0.062) and 0.83 (0.76-0.91, P < 0.001) among patients with IBS. Specifically, decreased risk of digestive (0.79 [0.71-0.89]), particularly colon (0.75 [0.62-0.90]) and rectal (0.68 [0.49-0.93]), cancers was observed in patients with IBS. Further sensitivity analysis and subgroup analysis by age and sex indicated similar results. Compared with the general population, IBS does not increase the overall risk of cancer. Conversely, IBS is associated with lower risk of incident colorectal cancer and cancer-specific mortality.

Coffee Intake of Colorectal Cancer Patients and Prognosis According to Histopathologic Lymphocytic Reaction and T-Cell Infiltrates

Given previous biologic evidence of immunomodulatory effects of coffee, we hypothesized that the association between coffee intake of colorectal cancer patients and survival differs by immune responses. Using a molecular pathologic epidemiology database of 4465 incident colorectal cancer cases, including 1262 cases with molecular data, in the Nurses’ Health Study and the Health Professionals Follow-up Study, we examined the association between coffee intake of colorectal cancer patients and survival in strata of levels of histopathologic lymphocytic reaction and T-cell infiltrates in tumor tissue. We did not observe a significant association of coffee intake with colorectal cancer–specific mortality (multivariable-adjusted hazard ratio [HR] for 1-cup increase of coffee intake per day, 0.93; 95% CI, 0.84 to 1.03). Although statistical significance was not reached at the stringent level (α=.005), the association of coffee intake with colorectal cancer–specific mortality differed by Crohn disease–like lymphoid reaction (Pinteraction=.007). Coffee intake was associated with lower colorectal cancer–specific mortality in patients with high Crohn disease–like reaction (multivariable HR for 1-cup increase of coffee intake per day, 0.55; 95% CI, 0.37 to 0.81; Ptrend=.002) but not in patients with intermediate Crohn disease–like reaction (the corresponding HR, 1.02; 95% CI, 0.72 to 1.44) or negative/low Crohn disease–like reaction (the corresponding HR, 0.95; 95% CI, 0.83 to 1.07). The associations of coffee intake with colorectal cancer–specific mortality did not significantly differ by levels of other lymphocytic reaction or any T-cell subset (Pinteraction>.18). There is suggestive evidence for differential prognostic effects of coffee intake by Crohn disease–like lymphoid reaction in colorectal cancer.

Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis.

Fusobacterium nucleatum (F. nucleatum) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis. We characterized F. nucleatum and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of nusA, nusG, and bacterial 16s rRNA genes in tumors from 1,994 patients with colorectal cancer and assessed associations between F. nucleatum presence and clinical characteristics, colorectal cancer-specific mortality, and somatic mutations. F. nucleatum, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies animalis. Presence of F. nucleatum was associated with higher colorectal cancer-specific mortality (HR, 1.97; P = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; P = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07-3.45; P = 0.029). Only F. nucleatum subspecies animalis, the main subspecies detected (65.8%), was associated with colorectal cancer-specific mortality (HR, 2.16; P = 0.0016), subspecies vincentii and nucleatum were not (HR, 1.07; P = 0.86). Additional adjustment for tumor stage suggests that the effect of F. nucleatum on mortality is partly driven by a stage shift. Presence of F. nucleatum was associated with microsatellite instable tumors, tumors with POLE exonuclease domain mutations, and ERBB3 mutations, and suggestively associated with TP53 mutations. F. nucleatum, and particularly subspecies animalis, was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes. Our findings identify the F. nucleatum subspecies animalis as negatively impacting colorectal cancer mortality, which may occur through a stage shift and its effect on chemoresistance.

Racial disparities in treatments and mortality among a large population-based cohort of older men and women with colorectal cancer

BackgroundThere were racial disparities in treatment and mortality among patients with colorectal cancer, but few studies incorporated information on hypertension and diabetes and their treatment status. Patients and methodsThe study identified 101,250 patients from Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in the United States who were diagnosed with colorectal cancer at age ≥65 years between 2007 and 2015 with follow-up to December 2016. ResultsThere were substantial racial and ethnic disparities in the prevalence of hypertension and diabetes in patients with colorectal cancer, in receiving chemotherapy and radiation therapy, and in receiving antihypertensive and antidiabetic treatment. Racial disparities in receiving these therapies remained significant in this large cohort of Medicare beneficiaries after stratifications by private health insurance status at the time of cancer diagnosis and by tumor stage. Non-Hispanic black patients had a significantly higher risk of all-cause mortality (hazard ratio: 1.07, 95% CI: 1.04–1.10), which remained significantly higher (1.05, 1.02–1.08) after adjusting for patient sociodemographics, tumor factors, comorbidity and treatments as compared to non-Hispanic white patients. The adjusted risk of colorectal cancer-specific mortality was also significantly higher (1.08, 1.04–1.12) between black and white patients. ConclusionsThere were substantial racial disparities in prevalence of hypertension and diabetes in men and women diagnosed with colorectal cancer and in receipt of chemotherapy, radiation therapy, antihypertensive and antidiabetic treatment. Black patients with colorectal cancer had a significantly higher risk of all-cause mortality and colorectal cancer-specific mortality than whites, even after adjusting for sociodemographic characteristics, tumor factors, comorbidity scores, and treatments.

Knowledge of primary and secondary colorectal cancer prevention among young people in Poland

Colorectal cancer-specific mortality in Poland exceeds the average for European Union countries. The aim of this study was to assess the knowledge about colorectal cancer and primary and secondary prevention. The original questionnaire was used in the study. 184 randomly selected respondents were included in the analysis (mean age 35 years). Only half of respondents knew the correct definition of screening test and only one-third of respondents correctly indicated the target group of Colorectal Cancer Screening Program in Poland. The main source of information about colorectal cancer was internet, rather than physicians and nurses. Lower knowledge of colorectal cancer was reported among respondents from small cities and villages, with less education and unemployed. The knowledge about colorectal cancer prevention is insufficient among polish population. Education seems to be an important part of health promotion, especially among people with low awareness of cancer risk factors and screening test.

Physical Activity after Colorectal Cancer Diagnosis and Mortality in a Nationwide Retrospective Cohort Study.

Simple SummaryPhysical activity can help to prevent colorectal cancer, but its importance after cancer diagnosis has not been validated. In this nationwide insurance data-based study of 43,596 colorectal cancer patients, a high level of physical activity after colorectal cancer diagnosis was negatively associated with a risk of death in both colon and rectal cancer patients, particularly in the surgically treated group. Our findings support the importance of the physical activity among colorectal cancer patients.Physical activity reduces the risk of colon cancer, but its prognostic impact after cancer diagnosis remains unclear. To evaluate the association between post-diagnosis activity and cause-specific mortality, we reconstructed a colorectal cancer patient cohort from the 2009–16 Korean National Health Insurance Service (NHIS) database. Subgroup analyses were performed by treatment group. In total, 27,143 colon cancer patients and 16,453 rectal cancer patients were included in the analysis (mean follow-up, 4.3 years; median 4.0 years). In the surgically treated group, a high level of activity (the weighted sum of the frequencies for walking, moderate, and vigorous activity greater than or equal to 3 times/week) was inversely associated with all-cause mortality (colon cancer: HR, 0.79; 95% CI, 0.72 to 0.88; rectal cancer: HR, 0.75; 95% CI, 0.66 to 0.86) and colorectal cancer-specific mortality (colon cancer: HR, 0.85; 95% CI, 0.76 to 0.97; rectal cancer: HR, 0.77; 95% CI, 0.66 to 0.90). No significant results were shown for cardiovascular disease-specific mortality. No association was shown in patients who received chemoradiotherapy without surgery. The present study may provide evidence for post-diagnosis physical activity as a prognostic factor in colorectal cancer, particularly in surgically treated early-stage patients.