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Current recommendations of The US Preventive Services Task Force (USPSTF) on colorectal cancer (CRC) screening strategies are based on models that assume 100% adherence. Since adherence can have a large effect on screening outcomes, we aimed to compare the effectiveness of CRC screening strategies under reported adherence rates at the population level. We developed and validated a microsimulation model to assess the effectiveness of colonoscopy (COL), flexible sigmoidoscopy (FS), high‐sensitivity guaiac fecal occult blood‐test (HS‐gFOBT), fecal immunochemical test (FIT), multitarget stool DNA test (FIT‐DNA), computed tomography colonography (CTC), and methylated SEPT9 DNA test (SEPT9) in terms of CRC incidence and mortality, incremental life years gained (LYG), number of colonoscopies, and adverse events for men and women 50 years or older over their lifetime. We assessed outcomes under 100% adherence rates and reported adherence rates. We also performed sensitivity analyses to evaluate the impact of varying adherence levels on CRC outcomes. Assuming 100% adherence, FIT‐DNA, FIT, HS‐gFOBT, and SEPT9 averted 42‐45 CRC cases and 25‐26 CRC deaths, COL 46 cases and 26 deaths, CTC 39 cases and 23 deaths, FS 32 cases and 19 deaths per 1000 individuals. Assuming reported adherence, SEPT9 averted 37 CRC cases and 23 CRC deaths, COL 34 cases and 20 deaths, FIT‐DNA, FIT, CTC and HS‐gFOBT 16‐25 cases and 10‐16 deaths per 1000 individuals. LYG reflected the effectiveness of each strategy in reducing CRC cases and deaths. Adverse events were more common for COL (3.7 per 1000 screened) and annual SEPT9 (3.4 per 1000 screened), and proportional to the number of colonoscopies. Among the screening strategies recommended by USPSTF, colonoscopy results in the largest benefit when we account for adherence. Adherence rates higher than 65%‐70% would be required for any stool or blood‐based screening modality to match the benefits of colonoscopy. [ABSTRACT FROM AUTHOR]

Background & Aims Microsatellite instability (MSI) in colorectal cancer cells results from deficient mismatch repair (MMR) protein function, either acquired or from germline alterations such as in patients with Lynch syndrome. Universal screening initiatives for Lynch syndrome have been encouraged. However, little is known about the true prevalence of MMR deficiency and MSI in colorectal tumors among individuals from different racial and ethnic subgroups or their clinical effects in these populations. Methods We performed a retrospective analysis of 253 surgically resected, primary colorectal adenocarcinoma specimens identified from the University of Miami tumor registry from 2005 through 2010. We collected clinical data, including overall survival (OS), the proportion of patients alive at specific intervals, from non-Hispanic white, Hispanic, and black patients matched by stage. We performed immunohistochemical staining to detect MMR proteins in all specimens and polymerase chain reaction analysis of 51 tumors to detect MSI. Results We detected MMR deficiency in 28 of 253 cases (11.1%), evenly distributed among blacks (9.6%), non-Hispanic whites (10.4%), and Hispanics (12.6%) ( P = .79). Combined deficiencies in MLH1 and PMS2 were found in 23 of 28 MMR-deficient samples (82.1%); MSH2 and MSH6 were most frequently absent in tumor samples from Hispanics ( P = .03). Eleven of 51 tumor samples (21.6%) had high levels of MSI, and we observed a high level of concordance between MMR and MSI (κ = .81). OS was significantly better in patients whose tumors had deficient MMR (hazard ratio for patients with MMR-deficient tumors vs MMR proteins intact = 0.37; 95% confidence interval, 0.15–0.91; P = .03). Race and ethnicity were not significant predictors of OS. Conclusions MMR deficiency in colorectal tumors occurs with similar rates among patients of different racial and ethnic groups, which is based on immunohistochemical analysis of 253 primary tumor specimens. This finding indicates the potential value of universal testing of colorectal cancer by immunohistochemistry in minority populations and confirms the benefit of MMR deficiency to OS. [ABSTRACT FROM AUTHOR]

Purpose: We examined individual-level and neighborhood-level predictors of mortality in CRC patients diagnosed in Florida to identify high-risk groups for targeted interventions. Methods: Demographic and clinical data from the Florida Cancer Data System registry (2007–2011) were linked with Agency for Health Care Administration and US Census data (n = 47,872). Cox hazard regression models were fitted with candidate predictors of CRC survival and stratified by age group (18–49, 50–64, 65+). Results: Stratified by age group, higher mortality risk per comorbidity was found among youngest (21%), followed by middle (19%), and then oldest (14%) age groups. The two younger age groups had higher mortality risk with proximal compared to those with distal cancer. Compared with private insurance, those in the middle age group were at higher death risk if not insured (HR = 1.35), or received healthcare through Medicare (HR = 1.44), Medicaid (HR = 1.53), or the Veteran’s Administration (HR = 1.26). Only Medicaid in the youngest (52% higher risk) and those not insured in the oldest group (24% lower risk) were significantly different from their privately insured counterparts. Among 18–49 and 50–64 age groups there was a higher mortality risk among the lowest SES (1.17- and 1.23-fold higher in the middle age and 1.12- and 1.17-fold higher in the older age group, respectively) compared to highest SES. Married patients were significantly better off than divorced/separated (HR = 1.22), single (HR = 1.29), or widowed (HR = 1.19) patients. Conclusion: Factors associated with increased risk for mortality among individuals with CRC included being older, uninsured, unmarried, more comorbidities, living in lower SES neighborhoods, and diagnosed at later disease stage. Higher risk among younger patients was attributed to proximal cancer site, Medicaid, and distant disease; however, lower SES and being unmarried were not risk factors in this age group. Targeted interventions to improve survivorship and greater social support while considering age classification may assist these high-risk groups. [ABSTRACT FROM AUTHOR]

Background Inflammation increases the risk of colorectal cancer (CRC). We and others have described a role for TLR4, the receptor for LPS, in colon cancer. To explore the relationships between TLR4 expression and CRC, we combined the strength of transcriptome array data and immunohistochemical (IHC) staining. Methods TLR4 signal intensity was scored in the stromal and epithelial compartments. Detection of differential expression between conditions of interest was performed using linear models, Cox proportional hazards models, and empirical Bayes methods. Results A strong association between TLR4 expression and survival was noted, though a dichotomous relationship between survival and specific TLR4 transcripts was observed. Increasing TLR4 expression was seen with advancing tumor stage and was also overexpressed in some adenomas. IHC staining confirmed the positive relationship between TLR4 staining score in the CRC tumor stroma and epithelium with tumor stage, with up to 47% of colon cancer stroma positive for TLR4 staining. Increased TLR4 expression by IHC was also marginally associated with decreased survival. We now also describe that pericryptal myofibroblasts are responsible for a portion of the TLR4 stromal staining. Conclusions Increased TLR4 expression occurs early in colonic neoplasia. TLR4 is associated with the important cancer-related outcomes of survival and stage. [ABSTRACT FROM AUTHOR]