Faculty Bibliography

BACKGROUND:Several US organizations now recommend starting average-risk colorectal cancer (CRC) screening at age 45 years, but the prevalence of colonic neoplasia in individuals younger than 50 years has not been well characterized. We used a national endoscopic registry to calculate age-stratified prevalence and predictors of colorectal neoplasia. METHODS:Outpatient screening colonoscopies performed during 2010-2020 in the GIQuIC registry were analyzed. We measured the prevalence of advanced neoplasia and adenomas by age, sex, and race/ethnicity, as well as the prevalence ratio (PR) of neoplasia compared to the reference group of 50-54 year-olds. Multivariable logistic regression models were used to identify predictors of neoplasia. RESULTS:We identified 3,928,727 screening colonoscopies, of which 129,736 (3.3%) were performed on average-risk individuals younger than 50 years. The prevalence of advanced neoplasia was 6.2% for 50-54 year-olds and 5.0% (PR 0.81, 95% CI 0.78-0.83) for average-risk 45-49 year-olds. Men had higher prevalence of neoplasia than women for all age groups. White individuals had higher prevalence of advanced neoplasia than persons of other racial/ethnic groups in most age groups, which was partially driven by serrated lesions. On multivariable regression, White individuals had higher odds of advanced neoplasia than Black, Hispanic, and Asian individuals in both younger and older age groups. CONCLUSIONS:In a large US endoscopy registry, the prevalence of advanced neoplasia in 45-49 year-olds was substantial and supports beginning screening at age 45 years. White individuals had higher risk of advanced neoplasia than Black, Hispanic, and Asian individuals across the age spectrum. These findings may inform adenoma detection benchmarks and risk-based screening strategies.

BACKGROUND/UNASSIGNED:In May 2021, the U.S. Preventive Services Task Force began recommending initiating colorectal cancer screening at age 45 (vs. 50) years. METHODS/UNASSIGNED:We estimated prevalence of colorectal cancer screening (by colonoscopy, sigmoidoscopy, CT colonography, or stool-based tests) in adults ages 50 to 75 years using data from the National Health Interview Survey in 2000, 2003, 2005, 2008, 2010, 2013, 2015, and 2018. For each survey year, we estimated prevalence by age, race/ethnicity, educational attainment, family income, and health insurance. We also compared increases in prevalence of screening from 2000 to 2018 in 5-year age groups (50-54, 55-59, 60-64, 65-69, and 70-75 years). RESULTS/UNASSIGNED:Overall, prevalence of colorectal cancer screening increased from 36.7% in 2000 to 66.1% in 2018. Screening prevalence in 2018 was lowest for age 50 to 54 years (47.6%), Hispanics (56.5%), Asians (57.1%), and participants with less than a high school degree (53.6%), from low-income families (56.6%), or without insurance (39.7%). Increases in prevalence over time differed by five-year age group. For example, prevalence increased from 28.2% in 2000 to 47.6% in 2018 (+19.4%; 95% CI, 13.1-25.6) for age 50 to 54 years but from 46.4% to 78.0% (+31.6%; 95% CI, 25.4%-37.7%) for age 70 to 75 years. This pattern was consistent across race/ethnicity, educational attainment, family income, and health insurance. CONCLUSIONS/UNASSIGNED:Prevalence of colorectal cancer screening remains low in adults ages 50 to 54 years. IMPACT/UNASSIGNED:As new guidelines are implemented, care must be taken to ensure screening benefits are realized equally by all population groups, particularly newly eligible adults ages 45 to 49 years.

BACKGROUND & AIMS/OBJECTIVE:Colorectal cancer (CRC) incidence has decreased overall in the last several decades, but it has increased among younger adults. Prior studies have characterized this phenomenon in the United States (U.S.) using only a small subset of cases. We describe CRC incidence trends using high-quality data from 92% of the U.S. population, with an emphasis on those younger than 50 years. METHODS:We obtained 2001 to 2016 data from the U.S. Cancer Statistics database and analyzed CRC incidence for all age groups, with a focus on individuals diagnosed at ages 20 to 49 years (early-onset CRC). We compared incidence trends stratified by age, as well as by race/ethnicity, sex, region, anatomic site, and stage at diagnosis. RESULTS:We observed 191,659 cases of early-onset and 1,097,765 cases of late-onset CRC during the study period. Overall, CRC incidence increased in every age group from 20 to 54 years. Whites were the only racial group with a consistent increase in incidence across all younger ages, with the steepest rise seen after 2012. Hispanics also experienced smaller increases in incidence in most of the younger age groups. Asians/Pacific Islanders and blacks saw no increase in incidence in any age group in 2016, but blacks continued to have the highest incidence of CRC for every age group. Greater increase in early-onset CRC incidence was observed for males, left-sided tumors, and regional and distant disease. CONCLUSIONS:Early-onset CRC incidence increased overall from 2001 to 2016, but the trends were markedly different for whites, blacks, Asians/Pacific Islanders, and Hispanics. These results may inform future research on the risk factors underlying early-onset CRC.

BACKGROUND:Incidence of colorectal cancer (CRC) among individuals aged less than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS), of 141 variants. METHODS:Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3,486 cases and 3,890 controls aged less than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve. RESULTS:Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per standard deviation of ERS = 1.14, 95% confidence interval [CI] = 1.08, 1.20; odds ratio per standard deviation of PRS = 1.59, 95% CI = 1.51, 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615, 0.647). Based on absolute risks, we can expect 26 excess cases per 10,000 men and 21 per 10,000 women, among those scoring at the 90th percentile for both risk scores. CONCLUSIONS:Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.

The multitarget stool DNA test with fecal immunochemical test (sDNA-FIT) is recommended by all major US guidelines as an option for colorectal cancer screening. It is approved by the Food and Drug Administration for use in average-risk individuals aged 45 years and older. The sDNA-FIT tests for 11 biomarkers, including point mutations in KRAS, aberrant methylation in NDRG4 and BMP3, and human hemoglobin. Patients collect a stool sample at home, send it to the manufacturer's laboratory within 1 day, and the result is reported in approximately 2 weeks. Compared with FIT, sDNA-FIT has higher sensitivity but lower specificity for colorectal cancer, which translates to a higher false-positive rate. A unique feature of sDNA-FIT is the manufacturer's comprehensive patient navigation system, which operates 24 hours a day and provides active outreach for patient education and reminders in the first month after a test is ordered. Retesting is recommended every 1-3 years, although the optimal testing interval has not yet been determined empirically. The cost of sDNA-FIT is $681 without insurance, but Medicare and most private insurers cover it with no copay or deductible.

Colorectal cancer screening incorporates various testing modalities. Factors including effectiveness, harms, cost, screening interval, patient preferences, and test availability should be considered when determining which test to use. Fecal occult blood testing and endoscopic screening have the most robust evidence, while newer blood- and imaging-based techniques require further evaluation. In this review, we compare the effectiveness, harms, and costs of the various screening strategies.

BACKGROUND:Use of the dietary supplement glucosamine has been associated with reduced risk of colorectal cancer (CRC); however, it remains unclear if the association varies by screening status, time, and other factors. METHODS:We therefore evaluated these questions in UK Biobank. Multivariable-adjusted Hazard Ratios (HRs) and 95% Confidence Intervals (95% CI) were estimated using Cox proportional hazards regression. RESULTS:No association was observed between use of glucosamine and risk of CRC overall (HR: 0.94; 95% CI: 0.85-1.04). However, the association varied by screening status (p-interaction:0.05), with an inverse association observed only among never-screened individuals (HR: 0.86; 95% CI: 0.76-0.98). When stratified by study time, an inverse association was observed in early follow-up among those entering the cohort in early years (2006-2008, HR: 0.80; 95% CI: 0.67-0.95). No heterogeneity was observed by age, sex, body mass index, smoking status, or use of non-steroidal anti-inflammatory drugs. CONCLUSIONS:While there was no association between glucosamine use and CRC overall, the inverse association among never-screened individuals mirrors our observations in prior exploratory analyses of US cohorts. The National Health Service Bowel Cancer Screening Program started in 2006 in England and was more widely implemented across the UK by 2009. In line with this, we observed an inverse association limited to early follow-up in those surveyed 2006-2008, before screening was widely implemented. IMPACT/CONCLUSIONS:These data suggest that unscreened individuals may benefit from use of glucosamine; however, further studies are needed to confirm the interplay of screening and timing.

INTRODUCTION/BACKGROUND:The Veterans Health Administration introduced a clinical reminder system in 2018 to help address process gaps in colorectal cancer screening, including the diagnostic evaluation of positive fecal immunochemical test (FIT) results. We conducted a qualitative study to explore the differences between facilities who performed in the top vs bottom decile for follow-up colonoscopy. METHODS:Seventeen semi-structured interviews with gastroenterology (GI) providers and staff were conducted at 9 high-performing and 8 low-performing sites. RESULTS:We identified 2 domains, current practices and perceived barriers, and most findings were described by both high- and low-performing sites. Findings exclusive to 1 group mainly pertained to current practices, especially arranging colonoscopy for FIT positive patients. We observed only 1 difference in the perceived barriers domain, which pertained to primary care providers. DISCUSSION/CONCLUSIONS:These results suggest that what primarily distinguishes high- and low-performing sites is not a difference in barriers, but rather in the GI clinical care process. Developing and disseminating patient education materials about the importance of diagnostic colonoscopy, eliminating in-person pre-colonoscopy visits when clinically appropriate, and involving GI in missed colonoscopy appointments and outside referrals should all be considered to increase follow-up colonoscopy rates. Our study illustrates the challenges of performing a timely colonoscopy after a positive FIT result and provides insights on improving the clinical care process for patients who are at substantially increased risk for colorectal cancer.