CRC-specific Mortality Research Articles

Alcohol consumption and smoking history at time of diagnosis, and risk of colorectal cancer recurrence and mortality: Results from the ColoCare Study.

Findings from studies investigating the impacts of alcohol use and smoking on colorectal cancer (CRC) outcomes are inconclusive. This study aimed to investigate associations between alcohol use and smoking status at the time of diagnosis on recurrence and overall mortality among patients with CRC. The present study included 2,216 stage I-IV patients with CRC from the longitudinal multi-center ColoCare study, with available data on recurrence and CRC-specific mortality. Cox proportional hazards models adjusted for age, sex, race, ethnicity, stage, tumor site, treatment, comorbidities, body mass index, and study site were fit, with imputations for missing data. We observed 235 recurrences and 308 CRC-specific deaths over an average of 3 years of follow-up. After adjusting for confounders, current alcohol consumption and ever smoking, relative to not current consumption and never smoking, respectively, were not statistically significantly associated with CRC recurrence (Alcohol - HR: 0.95. 95% CI: 0.71-1.29; Ever smoking - HR: 0.98, 95% CI: 0.75-1.29) or CRC-specific mortality (Alcohol - HR: 0.95. 95% CI: 0.74-1.22; Ever smoking - HR: 0.98, 95% CI: 0.77-1.24). No associations were observed between alcohol and smoking at diagnosis and clinical outcomes in this well-annotated longitudinal cohort. Our cohort study reports no significant associations; however, limiting alcohol use and avoiding smoking are health behaviors recommended for CRC survivors for prevention of other cancers and chronic conditions.

Associations of diabetes and mortality among colorectal cancer patients from the Southern Community Cohort Study.

We investigated associations between diabetes and mortality among participants with incident colorectal cancer (CRC) from the Southern Community Cohort Study. Participants (73% non-Hispanic Black; 60% income < $15,000) were recruited between 2002-2009. Diabetes was self-reported at enrollment and follow-up surveys at approximately 5-year intervals. Incident CRC and mortality were identified via state registries and the National Death Index. Proportional hazards models calculated associations between diabetes with overall, CRC-specific mortality among 1059 participants with incident CRC. Diabetes prior to diagnosis is associated with elevated overall (hazard ratio [95% confidence interval]: (1.46[1.22-1.75]), and CRC-specific mortality (1.36[1.06-1.74])) after adjustment for tumor stage. For non-Hispanic Black and non-Hispanic White participants, consistent associations were observed for overall (1.35[1.10-1.66] vs. 1.89[1.31-2.72], respectively, p-interaction = 0.11) and CRC-specific mortality (1.30[0.99-1.71] vs. 1.77[1.06-2.95], respectively, p-interaction = 0.28). For individuals with incomes <$15,000/year, associations with overall (1.44[1.15-1.79]) and CRC-specific mortality (1.28[0.94-1.73]) were similar to the full sample. Associations with overall (1.71[1.37-2.13]) and CRC-specific mortality (1.65[1.22-2.22]) were highest for diabetes ≥ 10 years at diagnosis. Pre-diagnosis diabetes is associated with higher mortality among participants with incident CRC from a predominantly non-Hispanic Black cohort with lower socioeconomic status. The higher prevalence of diabetes in this population may contribute to racial disparities in CRC mortality.

Higher levels of neighborhood deprivation and risk for incident colorectal cancer and mortality outcomes: A systematic review and meta-analysis.

131 Background: Significant geographic and racial disparities exist for colorectal cancer (CRC) incidence and mortality in the United States (US), which may be caused by neighborhood-level deprivation and limited access to preventative cancer screening. We completed the first systematic review and meta-analysis of neighborhood-level deprivation in relation to CRC incidence, mortality, and screening among individuals from the US. Methods: A systematic literature review was completed to identify original research articles from PubMed, Scopus, and Web of Science. Eligible studies reported associations between deprivation at the census block or tract level using a validated deprivation index (e.g. the Area Deprivation Index or Yost Index) and CRC incidence, mortality, or screening outcomes in a US-based sample. A fixed-effects meta-analysis was completed using inverse-variance weighting to estimated hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for CRC incidence, mortality, and screening outcomes, comparing the highest vs. lowest quantiles of neighborhood-level deprivation. All analyses were completed using the meta package in R. Results: In total, 19 studies were included in the meta-analysis. Living in a neighborhood in the highest quantile of deprivation was associated with significantly higher risk for incident CRC (HR 1.37, 95% CI 1.34-1.41, seven studies). In stratified analysis, positive associations with incident CRC were observed for White (HR 1.43, 95% CI 1.39-1.47, three studies), Black (HR 1.18, 95% CI 0.96-1.44, three studies), and Asian/Pacific Islander individuals (HR 1.18, 95% CI 1.08-1.28, two studies). For individuals diagnosed with CRC, higher deprivation was associated with elevated risk for overall mortality (HR 1.11, 95% CI 1.10-1.13, four studies) and CRC-specific mortality (HR 1.17, 95% CI 1.15-1.19, seven studies). Higher deprivation was associated with lower completion of recommended screening for CRC, including colonoscopy, sigmoidoscopy, or fecal occult blood testing (OR 0.76, 95% CI 0.74-0.79, four studies). Conclusions: Individuals who reside in neighborhoods with high levels of deprivation have significantly elevated risk for CRC incidence and mortality compared to individuals from low deprivation neighborhoods. Targeting healthcare resources to highly deprived neighborhoods to increase uptake of preventative screening may help to address racial and geographic disparities for CRC.

Prognostic Study of Colorectal Cancer: Differences between Screen-Detected and Symptom-Diagnosed Patients

Abstract: Background and objective: Colorectal cancer (CRC) is the leading cause of mortality in Spain, with screening programs, such as the faecal occult blood test and colonoscopy, having shown effectiveness in reducing CRC incidence and mortality. Despite these advancements, CRC screening uptake remains low in Spain, highlighting the need for studies comparing outcomes between screening-diagnosed and symptom-diagnosed patients to better understand the impact on overall survival and to quantify the clinical benefit in prognosis at diagnosis and at the end of follow-up. Methods: We conducted a retrospective cohort study with the following objectives: to compare stage at diagnosis, all-cause mortality, and disease-specific mortality among people diagnosed with CRC based on screening and based on symptoms; to identify the risk factors associated with mortality in this population; and to evaluate the effectiveness of screening on survival and early detection. Our study included people diagnosed with CRC in the public hospital of Elda (Spain) from 2014 to 2018; follow-up was until 2023 or death. Our primary outcome was all-cause mortality, which we analysed using Kaplan–Meier curves. We also investigated CRC-specific mortality and other-cause mortality. Results: Our sample included 315 people (186 with symptom-based diagnoses, 129 with screening-based diagnoses). The mean length of follow-up was 62.8 months. The screening group had a higher prevalence of a family history of CRC (p = 0.008), a distal tumour location (p = 0.002), and a cancer stage of 0 or I (p &lt; 0.001). The symptoms group had a higher prevalence of a proximal CRC (p = 0.002), other chronic diseases (p &lt; 0.001), and stages II, III, and IV (p &lt; 0.001). Two variables were associated with mortality: stage IV at diagnosis and previous cancers. People with a symptom-based diagnosis had a higher prevalence of stage IV at diagnosis and a higher cumulative incidence of CRC mortality and all-cause mortality at the end of follow-up (p &lt; 0.05). The Kaplan–Meier curves also showed a higher rate of all-cause mortality in the symptoms group throughout the follow-up. Conclusion: CRC screening enables an earlier diagnosis and improves survival. These findings support public health policies that promote accessible and effective screening.

Abstract C155: Differential colorectal cancer mortality across racial and ethnic groups: Impact of socioeconomic status, clinicopathology, and treatment-related factors

Abstract Introduction: Non-Hispanic Black colorectal cancer (CRC) patients have a higher risk of mortality compared to most other racial/ethnic groups. Limited studies examine the contribution of socioeconomic (SES), clinicopathologic, or treatment variations toward mortality disparities. This retrospective cohort investigation examined the extent to which SES, clinicopathologic, and treatment factors explain racial/ethnic differences in CRC mortality. Methods: We studied 146,515 individuals ,18+ years old, with a confirmed diagnosis of CRC within 2010-2017 identified from the Surveillance, Epidemiology, and End Results (SEER) database. We performed Cox regression analyses to examine the association of race/ethnicity, surgery type, and tumor site with all-cause mortality and CRC-specific mortality. We then performed mediation analysis to quantify the extent to which mortality differences were mediated by SES, clinicopathologic, and treatment factors. Results: Non-Hispanic Black patients had a significantly higher hazard of all-cause mortality than non-Hispanic White patients. The non- Hispanic White versus non-Hispanic Black patients’ comparison demonstrated that variations in SES and clinicopathologic factors significantly explained 46.63% (indirect effect HR: 0.92, 95% CI 0.91-0.93) and 10.87% (indirect effect HR: 0.98, 95% CI 0.97-99) of the excess all-cause mortality among non-Hispanic Black patients, respectively. The Hispanic vs. non-Hispanic Black comparisons identified SES as the most influential mediator, explaining 19.68% of the excess all-cause mortality. The proportions mediating for CRC-specific mortality showed comparable outcomes to all-cause mortality. Conclusions Non-Hispanic Black patients had greater risk for all-cause mortality and CRC-specific mortality attributed to SES and clinicopathologic variations compared to other racial/ethnic groups. Future studies should investigate equity in healthcare through interventions addressing SES-related disparities. Citation Format: Pierre Fwelo, Toluwani E. Adekunle, Tiwaladeoluwa B. Adekunle, Ella R. Garza, Emily S. Huang, Wayne R. Lawrence, Aldenise P. Ewing. Differential colorectal cancer mortality across racial and ethnic groups: Impact of socioeconomic status, clinicopathology, and treatment-related factors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C155.

Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients

BackgroundResearch on calcium intake as well as variants in the calcium sensor receptor (CaSR) gene and their interaction in relation to CRC survival is still limited.MethodsData from 18,952 CRC patients, were included. Associations between primarily pre-diagnostic dietary (n = 13.085), supplemental (n = 11,837), total calcium intake (n = 5970) as well as 325 single nucleotide polymorphisms (SNPs) of the CaSR gene (n = 15,734) in relation to CRC-specific and all-cause mortality were assessed using Cox proportional hazard models. Also interactions between calcium intake and variants in the CaSR gene were assessed.ResultsDuring a median follow-up of 4.8 years (IQR 2.4–8.4), 6801 deaths occurred, of which 4194 related to CRC. For all-cause mortality, no associations were observed for the highest compared to the lowest sex- and study-specific quartile of dietary (HR 1.00, 95%CI 0.92–1.09), supplemental (HR 0.97, 95%CI 0.89–1.06) and total calcium intake (HR 0.99, 95%CI 0.88–1.11). No associations with CRC-specific mortality were observed either. Interactions were observed between supplemental calcium intake and several SNPs of the CaSR gene.ConclusionCalcium intake was not associated with all-cause or CRC-specific mortality in CRC patients. The association between supplemental calcium intake and all-cause and CRC-specific mortality may be modified by genetic variants in the CaSR gene.

Investigating the Obesity Paradox in Colorectal Cancer: An Analysis of Prospectively Collected Data in a Diverse Cohort.

Prior studies are inconclusive regarding the effect of obesity on mortality in persons with colorectal cancer (CRC). We sought to determine the association of pre-diagnosis body mass index (BMI) trajectories on mortality after CRC diagnosis. Utilizing the Multiethnic Cohort, we included adults aged 18-75 between 1 January 1993 and 1 January 2019 with a diagnosis of CRC and at least three available BMIs. The primary exposure, BMI, was subjected to group-based trajectory modeling (GBTM). We evaluated all-cause and CRC-specific mortality, using Cox proportional hazard (PH) models. Of 924 persons, the median age was 60 years, and 54% were female. There was no statistically significant association between pre-cancer BMI trajectory and either all-cause or cancer-specific mortality. In competing risk analysis, the risk of CRC-specific mortality was higher for African Americans (HR = 1.56, 95% CI [1.00-2.43], p = 0.048) and smokers (HR = 1.59, 95% CI [1.10-2.32], p = 0.015). Risk of all-cause mortality was higher for Hawaiian persons (HR = 2.85, 95% CI [1.31-6.21], p = 0.009) and persons with diabetes (HR = 1.83, 95% CI [1.08-3.10], p = 0.026). Pre-diagnosis BMI trajectories were not associated with mortality after CRC diagnosis, whereas race/ethnicity, diabetes, and smoking were associated with an increased risk of death. Our findings suggest the obesity paradox alone does not account for mortality after CRC diagnosis.

Effect of statin use on long-term survival after diagnosis of colorectal cancer: Emulating hypothetical target trials using a nationwide real-world database.

82 Background: Observational studies suggest that statin use after colorectal cancer (CRC) diagnosis is associated with improved survival. However, potential bias due to misalignment of time zero in observational studies may distort associations and therefore requires validation using robust epidemiological methods. We aimed to emulate a hypothetical randomized trial—a target trial—for estimating per-protocol effects of statin initiation in patients with incident colorectal cancer on long-term survival. Methods: To emulate a target trial using real-world data, we extracted information from 103,005 patients diagnosed with CRC between 2005 and 2015 from the Korean National Health Insurance (KNHI) database, encompassing health records for the entire Korean population. We excluded individuals who had been prescribed statins for at least 180 days before the CRC diagnosis or those with missing or incomplete demographic information. We set a 180-day grace period and compared the group that initiated statin treatment within 180 days after the CRC diagnosis with the non-statin group using the “clone-censor-weight” method. Patients' demographic and socioeconomic information, along with colorectal cancer treatment, were included as baseline covariates. Additionally, the Charlson Comorbidity Index (CCI) score was included both as a baseline covariate and as a time-varying covariate. Hazard ratios (HRs) for all-cause mortality and CRC-specific mortality within 60 months of baseline were calculated using pooled logistic regression models. Results: Among the 103,005 patients diagnosed with CRC, 88,516 were finally analyzed after the exclusion process. A total of 2,071 (2.3%) individuals initiated statin treatment during the grace period and 86,445 (97.7%) patients did not. Statin initiators, compared with statin noninitiators tended to be older (mean age: 65.7 vs. 62.6) and had a higher CCI score at baseline (mean CCI score: 1.38 vs.1.26). Individuals who initiated statin treatment did not reduce the hazard of all-cause mortality (The adjusted HR 1.01, 95% CI 0.98-1.04) and CRC-specific mortality (The adjusted HR 1.01, 95% CI 0.97-1.04). Conclusions: The results of the analysis after removing potential biases showed that statin was not related to improving survival in CRC patients. The study results conflict with those of previous observational studies but are consistent with the findings of other recently conducted target trial emulations.

Conditional survival and the prognostic value of serum carcinoembryonic antigen level in oldest old with colorectal cancer

BackgroundTo evaluate the clinical value of serum CEA levels and their implications on the diagnostic value of the conventional TNM staging system in the oldest-old patients with colorectal cancer (CRC).MethodsThe recruited subjects were colorectal cancer patients aged 85 and older. The cutoff value for normal CEA level is 5 ng/mL. Patients with elevated CEA levels were categorized as stage C1, and those with normal CEA levels as stage C0. A number of Cox proportional hazard regression models were established to evaluate the prognosis of different prognostic factors with hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan–Meier method was utilized to display the disparate prognostic impact of multiple clinicopathological factors with the log-rank test.ResultsA total of 17,359 oldest-old patients diagnosed with CRC were recruited from the SEER database. The conditional survival of oldest-old patients with CRC was dismal with a 1-year conditional survival of only 11%, 18%, and 30% for patients surviving 1, 3, and 5 years, respectively. Patients with stage C1 exhibited a 48.5% increased risk of CRC-specific mortality compared with stage C0 (HR = 1.485, 95%CI = 1.393–1.583, using stage C0 patients as the reference, P < 0.001). All the stage C0 patients indicated lower HRs relative to the corresponding stage C1 patients.ConclusionsDismal conditional survival of oldest-old patients with CRC should be given additional consideration. C stage influences the prognosis of oldest-old patients with CRC.

Disaggregating U.S. Asian and Pacific Islanders: Colorectal cancer

BackgroundColorectal cancer remains a public health concern as the 4th most common cancer in the US. Incidence and mortality have been observed to differ between races; however, Asian and Pacific Islander ethnicities are often documented in aggregate. Recognizing that these groups are heterogeneous, this study seeks to disaggregate Native Hawaiian from the broader “Asian/Pacific Islander” group and examine disparate outcomes in colorectal cancer. MethodsDe-identified data from the Hawaii Tumor Registry was queried to evaluate colorectal cancer in the state of Hawaii. Primary outcomes were cancer stage at diagnosis, first course of therapies received, and duration of survival from diagnosis. Chi-square analyses were performed for differences in categorical variables. Results7943 Hawaii residents were diagnosed with colorectal cancer in 2008–2018 with 1151 (14.5 %) patients identifying as Native Hawaiian. Native Hawaiians were less likely to present with localized cancer (36.7 % vs. 41.7 %; p = 0.002) and more likely to be diagnosed with distant stage cancer compared to non-Native Hawaiians (25.2 % vs. 17.67 %; p < 0.0001) and, among those with distant metastases, more likely to receive chemotherapy (68.3 % vs. 61.1 %; p = 0.029). No significant differences were observed between races on analysis of CRC-specific mortality. ConclusionSignificant differences exist between disaggregated Asian and Pacific Islander ethnic groups. Native Hawaiians are observed to present with more advanced cancer at the time of diagnosis in comparison to ethnicities. Disaggregating these groups reveals racial and ethnic disparities that may inform public health measures. SynopsisDisaggregating Asian and Native Hawaiian and Pacific Islander groups reveals disparities in colorectal cancer. Native Hawaiians presented with more advanced disease across all studied ethnic groups. No significant differences were observed in colorectal cancer specific mortality across groups.

Longer Interval Between First Colonoscopy With Negative Findings for Colorectal Cancer and Repeat Colonoscopy

For individuals without a family history of colorectal cancer (CRC), colonoscopy screening every 10 years is recommended to reduce CRC incidence and mortality. However, debate exists about whether and for how long this 10-year interval could be safely expanded. To assess how many years after a first colonoscopy with findings negative for CRC a second colonoscopy can be performed. This cohort study leveraged Swedish nationwide register-based data to examine CRC diagnoses and CRC-specific mortality among individuals without a family history of CRC. The exposed group included individuals who had a first colonoscopy with findings negative for CRC at age 45 to 69 years between 1990 and 2016. The control group included individuals matched by sex, birth year, and baseline age (ie, the age of their matched exposed individual when the exposed individual's first colonoscopy with findings negative for CRC was performed). Individuals in the control group either did not have a colonoscopy during the follow-up or underwent colonoscopy that resulted in a CRC diagnosis. Up to 18 controls were matched with each exposed individual. Individuals were followed up from 1990 to 2018, and data were analyzed from November 2022 to November 2023. A first colonoscopy with findings negative for CRC, defined as a first colonoscopy without a diagnosis of colorectal polyp, adenoma, carcinoma in situ, or CRC before or within 6 months after screening. The primary outcomes were CRC diagnosis and CRC-specific death. The 10-year standardized incidence ratio and standardized mortality ratio were calculated to compare risks of CRC and CRC-specific death in the exposed and control groups based on different follow-up screening intervals. The sample included 110 074 individuals (65 147 females [59.2%]) in the exposed group and 1 981 332 (1 172 646 females [59.2%]) in the control group. The median (IQR) age for individuals in both groups was 59 (52-64) years. During up to 29 years of follow-up of individuals with a first colonoscopy with findings negative for CRC, 484 incident CRCs and 112 CRC-specific deaths occurred. After a first colonoscopy with findings negative for CRC, the risks of CRC and CRC-specific death in the exposed group were significantly lower than those in their matched controls for 15 years. At 15 years after a first colonoscopy with findings negative for CRC, the 10-year standardized incidence ratio was 0.72 (95% CI, 0.54-0.94) and the 10-year standardized mortality ratio was 0.55 (95% CI, 0.29-0.94). In other words, the 10-year cumulative risk of CRC in year 15 in the exposed group was 72% that of the 10-year cumulative risk of CRC in the control group. Extending the colonoscopy screening interval from 10 to 15 years in individuals with a first colonoscopy with findings negative for CRC could miss the early detection of only 2 CRC cases and the prevention of 1 CRC-specific death per 1000 individuals, while potentially avoiding 1000 colonoscopies. This cohort study found that for the population without a family history of CRC, the 10-year interval between colonoscopy screenings for individuals with a first colonoscopy with findings negative for CRC could potentially be extended to 15 years. A longer interval between colonoscopy screenings could be beneficial in avoiding unnecessary invasive examinations.

Ultra-processed food consumption and mortality among patients with stages I–III colorectal cancer: a prospective cohort study

Ultra-processed foods (UPFs) are emerging as a risk factor for colorectal cancer (CRC), yet how post-diagnostic UPF intake may impact CRC prognosis remains unexplored. Data collected from food frequency questionnaires were used to estimate intakes of total UPFs and UPF subgroups (serving/d) at least 6 months but less than 4 years post-diagnosis among 2498 patients diagnosed with stages I-III CRC within the Nurses' Health Study and Health Professionals Follow-up Study during 1980-2016. Hazard ratios (HR) and 95% confidence intervals (CIs) of all-cause, CRC- and cardiovascular disease (CVD)-specific mortality in association with UPF consumption were estimated using an inverse probability weighted multivariable Cox proportional hazards regression model, adjusted for confounders. The mean (SD) age of patients at diagnosis was 68.5 (9.4) years. A total of 1661 deaths were documented, including 321 from CRC and 335 from CVD. Compared to those in the lowest quintile (median=3.6 servings/d), patients in the highest quintile (median=10 servings/d) of post-diagnostic UPF intake had higher CVD mortality (HR=1.65, 95% CI=1.13-2.40) but not CRC or all-cause mortality. Among UPF subgroups, higher consumption of fats/condiments/sauces was associated with a higher risk of CVD-specific mortality (highest vs. lowest quintile of intake, HR=1.96, 95% CI=1.41-2.73), and higher intake of ice cream/sherbet was associated with an increased risk of CRC-specific mortality (highest vs. lowest quintile, HR=1.86, 95% CI: 1.33-2.61). No statistically significant association was found between UPF subgroups and overall mortality. Higher post-diagnostic intake of total UPFs and fats/condiments/sauces in CRC survivors is associated with higher CVD mortality, and higher ice cream/sherbet intake is linked to higher CRC mortality. US National Institutes of Health and the American Cancer Society.

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

BackgroundColorectal 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. MethodsWe 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. ResultsOverall, 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. ConclusionsIn 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.

Post-diagnostic multivitamin supplement use and colorectal cancer survival: A prospective cohort study.

Use of multivitamin supplements has been associated with lower incidence of colorectal cancer (CRC). However, its influence on CRC survival remains unknown. Among 2424 patients with stage I-III CRC who provided detailed information about multivitamin supplements in the Nurses' Health Study and Health Professionals Follow-up Study, the authors calculated multivariable hazard ratios (HRs) of multivitamin supplements for all-cause and CRC-specific mortality according to post-diagnostic use and dose of multivitamin supplements. During a median follow-up of 11years, the authors documented 1512 deaths, among which 343 were of CRC. Compared to non-users, post-diagnostic users of multivitamin supplements at a dose of 3-5 tablets/week had lower CRC-specific mortality (HR, 0.55; 95% confidence interval [CI], 0.36-0.83, p=.005), and post-diagnostic users at doses of 3-5 and 6-9 tablets/week had lower all-cause mortality (HR, 0.81; 95% CI, 0.67-0.99, p=.04; HR, 0.79; 95% CI, 0.70-0.88), p<.001). The dose-response analysis showed a curvilinear relationship for both CRC-specific (pnonlinearity < .001) and all-cause mortality (pnonlinearity=.004), with the maximum risk reduction observed at 3-5 tablets/week and no further reduction at higher doses. Compared to non-users in both pre- and post-diagnosis periods, new post-diagnostic users at dose of <10 tablets/week had a lower all-cause mortality (HR, 0.81; 95% CI, 0.71-0.94, p=.005), whereas new users at a dose of ≥10 tablets/week (HR, 1.58; 95% CI, 1.07-2.33) and discontinued users (HR, 1.35; 95% CI, 1.14-1.59) had a higher risk of mortality. Use of multivitamin supplements at a moderate dose after a diagnosis of nonmetastatic CRC is associated with lower CRC-specific and overall mortality, whereas a high dose (≥10 tablets/week) use is associated with higher CRC-specific mortality.

Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: Results from the European Prospective Investigation into Cancer and Nutrition study.

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine-Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HRQ4vsQ1 = 0.95, 95% CI: 0.73-1.23; Ptrend = .97; and HRper doubling of resistin concentration = 1.00; 95% CI: 0.84-1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

Warfarin intake in relation to diagnosis reduces mortality in patients with colorectal cancer – a register-based study

BackgroundSeveral studies have analyzed the effect of anticoagulants on cancer survival, with varying results. This study aimed to assess the effect of warfarin on survival in patients with colorectal cancer (CRC) in relation to timing of warfarin initiation. MethodsData on 10,051 individuals aged ≥45 years in the Västra Götaland Region of Sweden, and diagnosed with CRC between 2000 and 2009, were obtained from the Swedish National Cancer Register. Those who received warfarin treatment (n= 1,216) during the study period were labeled cases and those who did not (n= 8,873) were labeled controls. For statistical analysis, National Cancer Register data were merged with mortality data from the Swedish National Cause of Death register and data from the regional warfarin treatment register. ResultsHazard rates for CRC-specific mortality were lower in cases than in controls. When warfarin was used for any reason at any time, cases had a significantly lower CRC-specific mortality than controls among both women (hazard ratio [HR] 0.71; 95 % confidence interval [CI] 0.59–0.85; p= 0.0002) and men (HR 0.61; 95 % CI 0.52–0.72; p < 0001). Warfarin treatment after CRC diagnosis reduced CRC-specific mortality by 80 %; however, when warfarin was given before or ≥5 years after diagnosis, CRC-specific mortality did not significantly decrease. The number needed to treat to avoid one death was four. ConclusionUse of warfarin early after diagnosis in patients with CRC was associated with improved survival.

Vitamin C intake and colorectal cancer survival according to KRAS and BRAF mutation: a prospective study in two US cohorts.

The associations of vitamin C intake with colorectal cancer (CRC) survival according to tumour KRAS or BRAF mutation status remain unclear. We used the inverse probability weighted multivariable Cox proportional hazards regression model to calculate the hazard ratio (HR) of mortality, and spline analysis to evaluate the dose-response relationship in the Nurses' Health Study and Health Professionals Follow-up Study. We also assessed SLC2A1 mRNA expression according to KRAS or BRAF mutation in the TCGA database. During an average of 12.0 years of follow-up, we documented 2,096 CRC cases, of which 703 cases had KRAS and BRAF mutation data. The association between total vitamin C intake and CRC-specific mortality suggestively differed according to KRAS or BRAF mutation status (Pinteraction = 0.04), with the multivariable HR (95% CI) per 400 mg/day increase in vitamin C intake for CRC-specific mortality of 1.07 (0.87-1.32, Ptrend = 0.52) in cases with both wild type and 0.74 (0.55-1.00, Ptrend < 0.05) in cases with either KRAS or BRAF mutant type. TCGA analysis showed a higher mRNA SLC2A1 expression in KRAS or BRAF-mutated tumours than in wild-type tumours (P = 0.02). Our findings support the laboratory evidence for a potential benefit of vitamin C for CRC patients with KRAS or BRAF mutated tumours.

Association of pre-diagnostic physical exercise and peri-diagnostic body composition with mortality in non-metastatic colorectal cancer

PurposeSarcopenia and myosteatosis, quantified via computed tomography (CT), are associated with poor colorectal cancer outcomes. These body composition estimates can be influenced by physical exercise. We explored the correlation between pre-diagnostic physical exercise, body composition close to diagnosis, and the combined prognosis impact of these factors.MethodsWe studied 519 stage I–III colorectal cancer (CRC) cases diagnosed 2000–2016 with pre-diagnostic self-reported recreational physical exercise data collected in the prospective, population-based Northern Sweden Health and Disease Study, and CT-estimated skeletal muscle index (SMI) or skeletal muscle density (SMD). Risk estimates were calculated by multivariable logistic regression and Cox proportional hazards models.ResultsNo association was seen between low pre-diagnostic physical exercise and sarcopenia/myosteatosis in the multivariable model adjusted for age, sex, educational level, tumor stage, and tumor location. In multivariable Cox regression models, the combination of low pre-diagnostic physical exercise and either sarcopenia or myosteatosis at the time of diagnosis was associated with cancer-specific mortality compared to the reference group of high physical exercise combined with no sarcopenia/myosteatosis (adjusted HR 1.94 95% CI 1.00–3.76 for sarcopenia and adjusted HR 2.39 95% CI 1.16–4.94 for myosteatosis).ConclusionsThe combined presence of low pre-diagnostic physical exercise and sarcopenia or myosteatosis was associated with increased CRC-specific mortality. Despite the positive effect on prognosis, physical exercise did not alter body composition estimates at diagnosis, which could indicate attenuation from other factors.

Mortality After Postcolonoscopy Colorectal Cancer in the Veterans Affairs Health Care System

Postcolonoscopy colorectal cancer (PCCRC) refers to colorectal cancer (CRC) diagnosed after a colonoscopy in which no cancer was found and is reflective of colonoscopy quality at the individual and system levels. Colonoscopy is widely performed in the Veterans Affairs (VA) health care system, but the prevalence of PCCRC and its associated mortality are unknown. To examine PCCRC prevalence and its all-cause mortality (ACM) and CRC-specific mortality (CSM) within the VA health care system. This retrospective cohort study used VA-Medicare administrative data to identify 29 877 veterans aged 50 to 85 years with newly diagnosed CRC between January 1, 2003, and December 31, 2013. Patients whose colonoscopy occurred less than 6 months before CRC diagnosis with no other colonoscopy within the previous 36 months were categorized as having detected CRC (DCRC). Those who had a colonoscopy that did not detect CRC between 6 and 36 months before CRC diagnosis were categorized as having postcolonoscopy CRC (PCCRC-3y). A third group included patients with CRC and no colonoscopy within the prior 36 months. The final analysis of the data was performed in September 2022. Prior receipt of colonoscopy. Cox proportional hazards regression (with censoring, last follow-up December 31, 2018) analyses were conducted to compare PCCRC-3y and DCRC for 5-year ACM and CSM after CRC diagnosis. Of 29 877 patients with CRC (median [IQR] age, 67 [60-75] years; 29 353 [98%] male; 5284 [18%] Black, 23 971 [80%] White, and 622 [2%] other), 1785 (6%) were classified as having PCCRC-3y and 21 811 (73%) as having DCRC. The 5-year ACM rates were 46% vs 42% for patients with PCCRC-3y vs patients with DCRC. The 5-year CSM rates were 26% vs 25% for patients with PCCRC-3y vs patients with DCRC. In multivariable Cox proportional hazards regression analysis, there was no significant difference in ACM and CSM between patients with PCCRC-3y (adjusted hazard ratio [aHR], 1.04; 95% CI, 0.98-1.11; P = .18) and patients with DCRC (aHR, 1.04; 95% CI, 0.95-1.13; P = .42). However, compared with patients with DCRC, patients with no prior colonoscopy had significantly higher ACM (aHR, 1.76; 95% CI, 1.70-1.82; P < .001) and CSM (aHR, 2.22; 95% CI, 2.12-2.32; P < .001). Compared with patients with DCRC, patients with PCCRC-3y had significantly lower odds of having undergone colonoscopy performed by a gastroenterologist (odds ratio, 0.48; 95% CI, 0.43-0.53; P < .001). This study found that PCCRC-3y constituted 6% of CRCs in the VA system, which is similar to other settings. Compared with patients with CRC detected by colonoscopy, those with PCCRC-3y have comparable ACM and CSM.

Associations of advanced age with comorbidity, stage and primary subsite as contributors to mortality from colorectal cancer.

Although survival from colorectal cancer (CRC) has improved substantially in recent decades, people with advanced age still have a high likelihood of mortality from this disease. Nonetheless, few studies have investigated how cancer stage, subsite and comorbidities contribute collectively to poor prognosis of older people with CRC. Here, we decided to explore the association of age with mortality measures and how other variables influenced this association. Using linkage of several administrative datasets, we investigated the risk of death among CRC cases during 2003-2014. Different models were used to explore the association of age with mortality measures and how other variables influenced this association. Our results indicated that people diagnosed at a young age and with lower comorbidity had a lower likelihood of all-cause and CRC-specific mortality. Aging had a greater association with mortality in early-stage CRC, and in rectal cancer, compared that seen with advanced-stage CRC and right colon cancer, respectively. Meanwhile, people with different levels of comorbidity were not significantly different in terms of their increased likelihood of mortality with advanced age. We also found that while most comorbidities were associated with all-cause mortality, only dementia [SHR = 1.43 (1.24-1.64)], Peptic ulcer disease [SHR = 1.12 (1.02-1.24)], kidney disease [SHR = 1.11 (1.04-1.20)] and liver disease [SHR = 1.65 (1.38-1.98)] were risk factors for CRC-specific mortality. This study showed that the positive association of advanced age with mortality in CRC depended on stage and subsite of the disease. We also found only a limited number of comorbidities to be associated with CRC-specific mortality. These novel findings implicate the need for more attention on factors that cause poor prognosis in older people.