Differences In Colorectal Cancer Incidence Research Articles

Abstract 3453: U.S. Geographic and socio-demographic characteristics of Voyage Study participants

Abstract The Voyage Study is a large-scale, prospective cohort study of long-term health outcomes among participants with a valid multi-target stool DNA (mt-sDNA) test order. Recently, the Voyage Study achieved its enrollment target of 150,000 participants. The intent of this descriptive analysis is to provide baseline geographic and socio-demographic characteristics of Voyage Study participants to set the stage for future comparisons to the broader mt-sDNA user population. Participants were randomly selected from all persons in the U.S. or Puerto Rico who had a valid order for mt-sDNA screening during the enrollment period (10/18/2019 - 10/17/2023). Enrolled participants completed a baseline questionnaire that collected socio-demographic and health information. Participant characteristics and baseline survey answers were compared between regions using chi-square tests where appropriate. Regional geographic data was aggregated for the broader mt-sDNA user population during the enrollment period, though no formal comparisons were made between the broader population and the Voyage population at this time. Analyses were limited to 139,369 participants with available baseline questionnaire data. Voyage participants were more likely to reside in the Midwest, Northeast, or Southeast (29.9%, 22.5%, 22.6% respectively) and less likely to reside in the Southwest and West (11.6%, 13.4%). During the enrollment period, differential participation was also observed in the mt-sDNA user population, with the Midwest, Northeast, and Southeast having the greatest proportion (25.4%, 22.2%, 26.7%) and the Southwest and West having the lowest proportion of mt-sDNA users (13.8%, 11.9%). In the Voyage cohort, Midwest participants reported the lowest education attainment as characterized by years of school completed (14.1% high school or below, 59.2% college or greater), while participants in the West reported the highest education attainment (7.9% high school or below, 67.3% college or greater). The West also had the highest percentage of participants reporting an income of $100,000 or greater (51.6%), with the Southeast being the lowest (42.2%), as compared to the other regions. We report here early results of geographic and socio-demographic characteristics from a new research resource that will enable future analyses of health outcomes and behaviors in a population of mt-sDNA users. We observed that the greatest percentage of Voyage participants resided in the Midwest, Northeast, or Southeast, and that there was differential socio-demographic participant characteristics based on region. Future analyses will compare long-term healthcare outcomes and differences in colorectal cancer incidence and mortality between the broader mt-sDNA user population and the Voyage cohort. Citation Format: Allison M. Berry, Jessica A. Grimm, Christine R. Kirt, Emily J. Kirsch, Rachel E. Dixon, Winnie Z. Fan, Kandace A. Bohn, Jennifer St. Sauver, Kathleen J. Yost, Lila J. Finney Rutten, Janet E. Olson. U.S. Geographic and socio-demographic characteristics of Voyage Study participants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3453.

Survival by race and ethnicity among insured patients with early-onset colorectal cancer.

18 Background: Colorectal cancer (CRC) incidence and mortality have decreased in the United States over the past 3 decades, but the incidence is increasing in those <50 years of age (i.e., early-onset CRC). Studies have examined racial and ethnic differences in CRC incidence in this age group, but little is known about differences in survival. Examining survival by race and ethnicity among patients with early-onset CRC may provide insights about differences in risk factors, access to care, and treatment. Methods: This retrospective cohort study included Kaiser Permanente Northern California health plan members 18-49 years of age and diagnosed with CRC between 2006-2019. Race and ethnicity were self-reported as Asian/Pacific Islander, Black, Hispanic, or White. 5-year survival probability was assessed using Kaplan-Meier analyses. Cox regression with adjustment was used to evaluate associations between race and ethnicity and 5-year survival. Results: Of 1620 patients, median age was 45.4 years, 47% were female, 20% were Asian/Pacific Islander, 8% Black, 22% Hispanic, and 50% non-Hispanic White persons. Adjusted for age, sex, and comorbidities, Hispanic persons had a higher risk of death at 5 years compared to White persons (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.09-1.83) (Table). Sequentially adding annual household income and neighborhood deprivation index had no impact on the association; adding tumor stage decreased the HR to 1.14 (0.87-1.49) and adding tumor and treatment factors decreased the HR to 1.08 (0.82-1.42). Risk of death among Asian/Pacific Islander and Black patients did not differ from White patients. Conclusions: Among insured patients with early-onset CRC, Hispanic patients had a higher risk of death at 5 years than patients of White race. The higher risk was associated with differences in tumor stage at diagnosis, tumor factors, and treatment factors. Targeted interventions to improve CRC symptom awareness and remove barriers to CRC diagnosis and treatment among vulnerable populations may be needed to eliminate disparities in early-onset CRC survival. [Table: see text]

Black-White disparities in colorectal cancer outcomes: a simulation study of screening benefit.

The US Black population has higher colorectal cancer (CRC) incidence rates and worse CRC survival than the US White population, as well as historically lower rates of CRC screening. The Surveillance, Epidemiology, and End Results incidence rate data in people diagnosed between the ages of 20 and 45 years, before routine CRC screening is recommended, were analyzed to estimate temporal changes in CRC risk in Black and White populations. There was a rapid rise in rectal and distal colon cancer incidence in the White population but not the Black population, and little change in proximal colon cancer incidence for both groups. In 2014-2018, CRC incidence per 100 000 was 17.5 (95% confidence interval [CI] = 15.3 to 19.9) among Black individuals aged 40-44 years and 16.6 (95% CI = 15.6 to 17.6) among White individuals aged 40-44 years; 42.3% of CRCs diagnosed in Black patients were proximal colon cancer, and 41.1% of CRCs diagnosed in White patients were rectal cancer. Analyses used a race-specific microsimulation model to project screening benefits, based on life-years gained and lifetime reduction in CRC incidence, assuming these Black-White differences in CRC risk and location. The projected benefits of screening (via either colonoscopy or fecal immunochemical testing) were greater in the Black population, suggesting that observed Black-White differences in CRC incidence are not driven by differences in risk. Projected screening benefits were sensitive to survival assumptions made for Black populations. Building racial disparities in survival into the model reduced projected screening benefits, which can bias policy decisions.

Improvement of a clinical colorectal cancer risk prediction model integrating polygenic risk.

81 Background: Improving colorectal cancer risk prediction and stratification is pivotal for implementing better screening and prevention programs in public health and for enabling a personalised approach for assessing patients’ colorectal cancer risk. Methods: In this study, we used the UK Biobank to compare the performance of a risk prediction model incorporating two different polygenic risk scores – one comprising 45 SNPs and the other comprising 140 SNPs. The clinical component of the risk prediction model included a simple measure of first-degree family history. We used age- and sex-specific population incidence rates to calculate full-lifetime risks. Results: The model using the 140-SNP PRS showed an improvement in discrimination, calibration and risk stratification over the model using the 45-SNP PRS for full-lifetime risk: discrimination was 0.706 (95% CI 0.697–0.715) and 0.674 (95% CI 0.664–0.683), respectively, and the P for difference was < 0.001. The 140-SNP model was well calibrated and showed a small overestimation of risk 0.951 (95% CI 0.918–0.986). Standard incidence ratios compared to population incidence rates showed that, for the 140-SNP model, the top quintile of risk shows a 27% improvement compared to the 45-SNP model. Furthermore, there was a 3-fold difference in colorectal cancer incidence between adults identified in the top quintile compared to the bottom quintile of risk using the 140-SNP model versus the 45-SNP model. Conclusions: This updated risk prediction score with a 140–SNP PRS and a simple measure of family history, improves risk prediction and risk stratification in the general population compared with a similar model with a 45-SNP PRS, and will ultimately assist in colorectal cancer disease prevention in the clinic.

Colorectal cancer incidence and survival inequalities among labour immigrants in Belgium during 2004–2013

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality. We aim to map out differences in CRC incidence and survival between first-generation traditional labour immigrants of Italian, Turkish and Moroccan descent and native Belgians; and assess the contribution of socioeconomic position (SEP) to these differences. Individually-linked data of the 2001 Belgian Census, the Crossroads Bank for Social Security and the Belgian Cancer Registry are used. Age-standardized incidence rates and incidence rate ratios are calculated by country of origin, with and without adjusting for SEP. For CRC patients, 5-year relative survival rates and the relative excess risk for dying within five years after diagnosis are calculated by migrant origin. Lower CRC incidence was observed among immigrants compared to native Belgians, in particular among non-Western immigrants, which could not be explained by SEP. Survival inequalities were less clear, yet, after adjusting for age and stage at diagnosis and educational attainment, we observed a survival advantage among Turkish and Italian immigrant men. Health gains can be made for the native population by adapting lifestyle. The later stage at diagnosis for immigrants is of concern. Barriers regarding screening as perceived by the vulnerable groups should be identified.

Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial: Planned 10-Year Follow-up.

The CAPP2 trial investigated the long-term effects of aspirin and resistant starch on cancer incidence in patients with Lynch syndrome (LS). Participants with LS were randomized double-blind to 30 g resistant starch (RS) daily or placebo for up to 4 years. We present long-term cancer outcomes based on the planned 10-year follow-up from recruitment, supplemented by National Cancer Registry data to 20 years in England, Wales, and Finland. Overall, 463 participants received RS and 455 participants received placebo. After up to 20 years follow-up, there was no difference in colorectal cancer incidence (n = 52 diagnosed with colorectal cancer among those randomized to RS against n = 53 on placebo) but fewer participants had non-colorectal LS cancers in those randomized to RS (n = 27) compared with placebo (n = 48); intention-to-treat (ITT) analysis [HR, 0.54; 95% confidence interval (CI), 0.33-0.86; P = 0.010]. In ITT analysis, allowing for multiple primary cancer diagnoses among participants by calculating incidence rate ratios (IRR) confirmed the protective effect of RS against non-colorectal cancer LS cancers (IRR, 0.52; 95% CI, 0.32-0.84; P = 0.0075). These effects are particularly pronounced for cancers of the upper GI tract; 5 diagnoses in those on RS versus 21 diagnoses on placebo. The reduction in non-colorectal cancer LS cancers was detectable in the first 10 years and continued in the next decade. For colorectal cancer, ITT analysis showed no effect of RS on colorectal cancer risk (HR, 0.92; 95% CI, 0.62-1.34; P = 0.63). There was no interaction between aspirin and RS treatments. In conclusion, 30 g daily RS appears to have a substantial protective effect against non-colorectal cancer cancers for patients with LS. Regular bowel screening and aspirin reduce colorectal cancer among patients with LS but extracolonic cancers are difficult to detect and manage. This study suggests that RS reduces morbidity associated with extracolonic cancers. See related Spotlight, p. 557.

The impact of cumulative colorectal cancer screening delays: A simulation study.

Annual fecal immunochemical tests can reduce colorectal cancer incidence and mortality. However, screening is a multi-step process and most patients do not perfectly adhere to guideline-recommended screening schedules. Our objective was to compare the reduction in colorectal cancer incidence and life-years gained based on US guideline-concordant fecal immunochemical test screening to scenarios with a range of delays. The Colorectal Cancer Simulated Population model for Incidence and Natural history (CRC-SPIN) microsimulation model was used to estimate the effect of systematic departures from fecal immunochemical test screening guidelines on lifetime screening benefit. The combined effect of consistent modest delays in screening initiation (1 year), repeated fecal immunochemical test screening (3 months), and receipt of follow-up or surveillance colonoscopy (3 months) resulted in up to 1.3 additional colorectal cancer cases per 10,000, 0.4 additional late-stage colorectal cancer cases per 10,000 and 154.7 fewer life-years gained per 10,000. A 5-year delay in screening initiation had a larger impact on screening effectiveness than consistent small delays in repeated fecal immunochemical test screening or receipt of follow-up colonoscopy after an abnormal fecal immunochemical test. The combined effect of consistent large delays in screening initiation (5 years), repeated fecal immunochemical test screening (6 months), and receipt of follow-up or surveillance colonoscopy (6 months) resulted in up to 3.7 additional colorectal cancer cases per 10,000, 1.5 additional late-stage colorectal cancer cases per 10,000 and 612.3 fewer life-years gained per 10,000. Systematic delays across the screening process can result in meaningful reductions in colorectal cancer screening effectiveness, especially for longer delays. Screening delays could drive differences in colorectal cancer incidence across patient groups with differential access to screening.

Characteristics of colorectal cancers among Alaska Native people before and after implementing programs to promote screening

BackgroundAlaska Native (AN) people have the highest rates of colorectal cancer (CRC) globally. Increasing CRC screening has been effective in reducing CRC-related morbidity and mortality in other populations. ObjectiveTo examine recent descriptive epidemiology and longer-term CRC trends among AN people. To determine any changes in the descriptive epidemiology of CRC among AN people concurrent with increases in screening prevalence.Methods: We estimated age-specific CRC incidence and mortality rates 2000−2017. To examine longer-term trends in incidence and mortality 1990–2017, we conducted Joinpoint regression analyses of three-year rolling average incidence and mortality rates. We calculated descriptive statistics for two time-periods: 2000−2008, and 2009−2017. Finally, we examined five-year survival probability. ResultsCRC incidence increased over time (1990–2017) among AN people aged less than 50 years, while there were modest declines in AN people older than 50 years old since 2000. Overall, AN CRC mortality rates declined between 1990 and 2004, but have been increasing steadily since that time. Comparing 2000−2008 with 2009−2017 we observed no difference in CRC incidence and mortality, age at diagnosis, tumor size, tumor location, or stage distribution. Survival analyses indicated no change in hazard of death between 2004−2008 and 2009−2017 (HR 1.02, 95 % CI: 0.74, 1.38, P = 0.93). ConclusionsColorectal cancer prevention and control efforts across the Alaska Tribal Health System have not yet resulted in reduced mortality rates, or induced earlier stage migration. Policy summary statementIntensified efforts will be necessary to reduce the burden of CRC among this high-risk population. Continued and increased focus on primary and secondary prevention efforts is warranted.

P-216 Gender-specific genomic alterations among Hispanic patients with metastatic colorectal cancer

Colorectal cancer (CRC) the third most common cause of cancer among men and women in the USA. In 2021, an estimated 147,950 new cases of CRC will be diagnosed in the US, and 53,200 people will die from CRC. The incidence of CRC among Hispanics living in the USA varies according to their country of origin, supporting the idea that differences in ancestry may contribute to the differences in CRC incidence. For unclear reasons, the incidence of CRC is dramatically increasing among younger Hispanics.

The effect of aspirin on colorectal cancer incidence in African Americans.

4085 Background: From 2011 to 2016, the incidence and mortality rate of colorectal cancer(CRC) were highest among African Americans(AA), compared to other US racial/ethnic groups. Long-term aspirin use is recommended as a strategy to reduce the risk of CRC. Yet, there is scant information on the chemopreventive effect of aspirin among AA. It is imperative to assess whether the reported chemo-preventive effect also occurs in AA. Our central hypothesis is that aspirin use in AA is associated with a lower incidence of CRC, irrespective of race/ethnicity. Methods: We conducted a secondary analysis, using data from AA participants in the Atherosclerosis Risk in Communities(ARIC) longitudinal study, who did not have CRC at enrollment, from 1987 to 1998. We extracted demographic, clinical and mortality data to compare the incidence of CRC among participants taking aspirin compared to those who were not taking aspirin, stratified by age, tobacco use, and body mass index. All-cause mortality and CRC mortality will also be assessed, and we will use Cox proportional hazard regression to determine the relationship between aspirin use and CRC incidence, and mortality. Results: At baseline in 1987, 15,026 participants enrolled in the ARIC study, 25% of whom were AA, median age 54(range 44-66), including 46.7% who reported using aspirin. We analyzed follow-up data from 10,960 participants in 1996-1998, 20% of whom were AA, and 56.9% of whom were taking aspirin. Non-AA participants were more likely to report using aspirin at baseline and follow-up, compared to AA, 53% vs 30% and 59% vs 50% respectively. After 10years, the total incidence of CRC in AA participants was 1% compared with 1.1% in non-AA(p = 0.7). There was no difference in CRC incidence by aspirin use among all participants, and when stratified by race(among all participants p = 0.81, amongAA p = 0.68, among non-AA p = 0.94). Conclusions: We found no difference in the incidence of CRC among AA compared to Caucasians, by aspirin use. Investigation of consistency and/or dose of aspirin use by race may provide further insights on the relationship between aspirin use and CRC incidence, comparing AA to Caucasians.

Exploring geographical differences in the incidence of colorectal cancer in the Norwegian Women and Cancer Study: a population-based prospective study.

PurposeNorway has experienced an unexplained, steep increase in colorectal cancer (CRC) incidence in the last half-century, with large differences across its counties. We aimed to determine whether geographical distribution of lifestyle-related CRC risk factors can explain these geographical differences in CRC incidence in Norwegian women.MethodsWe followed a nationally representative cohort of 96,898 women with self-reported information on lifestyle-related CRC risk factors at baseline and at follow-up 6–8 years later in the Norwegian Women and Cancer Study. We categorized Norwegian counties into four county groups according to CRC incidence and used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk factors. We used the Karlson, Holm, and Breen (KHB) method of mediation analysis to investigate the extent to which the risk factors accounted for the observed differences in CRC incidence between counties.ResultsDuring an average of 15.5 years of follow-up, 1875 CRC cases were diagnosed. Height (HR=1.12; 95% CI 1.08, 1.17 per 5 cm increase); being a former smoker who smoked ≥10 years (HR=1.34; 95% CI 1.15, 1.57); or being a current smoker who has smoked for ≥10 years (HR=1.28; 95% CI 1.12, 1.46) relative to never smokers was associated with increased CRC risk. Duration of education >12 years (HR=0.78; 95% CI 0.69, 0.87) vs ≤12 years, and intake of vegetables and fruits >300 g (HR=0.90; 95% CI 0.80, 0.99) vs ≤300 g per day were associated with reduced CRC risk. However, these risk factors did not account for the differences in CRC risk between geographical areas of low and high CRC incidence. This was further confirmed by the KHB method using baseline and follow-up measurements (b=0.02, 95% CI −0.02, 0.06, p=0.26).ConclusionLifestyle-related CRC risk factors did not explain the geographical variations in CRC incidence among Norwegian women. Possible residual explanations may lie in heritable factors.

Gender-Related Differences in the Incidence and Mortality of Late-Onset Colorectal Cancer: Estimates Based on the PLCO Cohort Study

Background: Gender differences in colorectal cancer (CRC) are more pronounced among older adults (age ≥55 years), and few studies have comprehensively investigated variations in this age group. It is important to investigate patterns of age- and gender-driven differences in CRC incidence and mortality among older adults. Methods: We evaluated gender differences in CRC incidence and mortality utilizing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (126,291 subjects). The effect of gender differences on older adults was further confirmed in the Surveillance, Epidemiology, and End Results (SEER) database for (442,104 CRC cases). Incidence rate ratio (IRR) and mortality rate ratio (MRR) were estimated using Poisson regression models. Findings: We found that the IRR (male: female) increased from 1.33 at 55-59 years (33% higher in males) to 1.63 at 70-74 years (63% higher in males), even after adjusting for confounders. A similar trend of male predominance in CRC incidence was also observed in SEER (IRR=1.38-1.47, P<0.05). In particular, we observed that compared with age-matched females, older males were more likely to be diagnosed with left-sided, early-stage, and well/moderately differentiated CRC. The gender differences in CRC incidence were significant in nonsmoking subjects, normal weight/overweight subjects and subjects without a family history of CRC. Compared with age-matched females, males aged 70-74 years had a greater risk of fatal CRC (MRR=1.79, P<0.05). Interpretation: Understanding gender differences in CRC incidence and mortality may offer novel preventive strategies. Further functional studies are required to reveal the mechanisms underlying gender differences in CRC incidence and mortality. Funding: This study was supported by the National Key R&D Program of China (2017YFC0908200), the National Natural Science Foundation of China (81822039, 81872697, 81773516), the Foundation of Six Talent Peaks Project of Jiangsu (YY-020), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine). Declaration of Interest: The authors declare no competing interests. Ethical Approval: Both study protocols were authorized by the ethics committees of the data providers and our university.

Disparities in colorectal cancer between Northern and SouthernSweden – a report from the new RISK North database

Background: Geographic cancer health disparities have been reported in Sweden. The disparities are not fully understood, but may be attributed to differences in exposure to risk factors as well as differences in health care, socioeconomics and demography. The aim of this study was to describe the new nationwide population based RISK North database and its potential by analysing health disparities in colorectal cancer between Northern and Southern Sweden.Methods: Cancer-specific data from the National Cancer Quality Registers for colorectal, gastric and oesophageal cancer and brain tumours were linked to several nationwide registers hereby creating a new database – RISK North. To exemplify the potential of RISK North, we analyzed differences in colorectal cancer incidence, mortality and survival in relation to gender, age, cohabitation and education between Northern and Southern Sweden 2007–2013.Results: In colon cancer, the age-adjusted incidence per 100.000 was lower in Northern than Southern Sweden, 35.9 in the North vs. 41.1 in the South (p < .01); mortality rates were 11.0 vs. 12.2 (p < .01). For rectal cancer, incidence rates were 17.6 vs. 19.7 (p < .01) and mortality rates 5.33 vs. 5.89 (p = .07), respectively. The largest difference in incidence was demonstrated for colon cancer among individuals >79 years old (190. vs. 237, i.e., ∼20%). Survival in colon cancer was higher in Southern Sweden, HR 0.92 (0.87–0.98) adjusted for age, gender, co-habiting, education and m-stage at diagnosis. No difference in survival was seen for rectal cancer.Conclusions: The new RISK North database enabled analysis of cancer disparities between Northern and Southern Sweden. The incidence of colorectal cancer were lower in the North of Sweden whereas colon cancer survival was higher in the South. These differences can be further analysed utilising the RISK North database.

A review of sex-related differences in colorectal cancer incidence, screening uptake, routes to diagnosis, cancer stage and survival in the UK

BackgroundColorectal cancer (CRC) is an illness strongly influenced by sex and gender, with mortality rates in males significantly higher than females. There is still a dearth of understanding on where sex differences exist along the pathway from presentation to survival. The aim of this review is to identify where actions are needed to improve outcomes for both sexes, and to narrow the gap for CRC.MethodsA cross-sectional review of national data was undertaken to identify sex differences in incidence, screening uptake, route to diagnosis, cancer stage at diagnosis and survival, and their influence in the sex differences in mortality.ResultsOverall incidence is higher in men, with an earlier age distribution, however, important sex differences exist in anatomical site. There were relatively small differences in screening uptake, route to diagnosis, cancer staging at diagnosis and survival. Screening uptake is higher in women under 69 years. Women are more likely to present as emergency cases, with more men diagnosed through screening and two-week-wait. No sex differences are seen in diagnosis for more advanced disease. Overall, age-standardised 5-year survival is similar between the sexes.ConclusionsAs there are minimal sex differences in the data from routes to diagnosis to survival, the higher mortality of colorectal cancer in men appears to be a result of exogenous and/or endogenous factors pre-diagnosis that lead to higher incidence rates. There are however, sex and gender differences that suggest more targeted interventions may facilitate prevention and earlier diagnosis in both men and women.

No Difference in Colorectal Cancer Incidence or Stage at Detection by Colonoscopy Among 3 Countries With Different Lynch Syndrome Surveillance Policies

Patients with Lynch syndrome are at high risk for developing colorectal cancer (CRC). Regular colonoscopic surveillance is recommended, but there is no international consensus on the appropriate interval. We investigated whether shorter intervals are associated with lower CRC incidence and detection at earlier stages by comparing the surveillance policies in Germany, which evaluates patients by colonoscopy annually, in the Netherlands (patients evaluated at1-2-year intervals), and Finland (patients evaluated at 2-3-year intervals). We collected data from 16,327 colonoscopic examinations (conducted from 1984 through 2015) of 2747 patients with Lynch syndrome (pathogenic variants in the MLH1, MSH2, or MSH6 genes) from the German HNPCC Consortium, the Dutch Lynch Syndrome Registry, and the Finnish Lynch Syndrome Registry. Our analysis included 23,309 person-years of cumulative observation time. Time from the index colonoscopy to incident CRC or adenoma was analyzed using the Kaplan-Meier method; groups were compared using the log-rank test. We performed multivariable Cox regression analyses to identify factors associated with CRC risk (diagnosis of CRC before the index colonoscopy, sex, mutation, age, and presence of adenoma at the index colonoscopy). The 10-year cumulative CRC incidence ranged from 4.1% to 18.4% in patients with low- and high-risk profiles, respectively, and varied with age, sex, mutation, and prior detection of CRC or adenoma. Observed colonoscopy intervals were largely in accordance with the country-specific recommendations. We found no significant differences in cumulative CRC incidence or CRC stage at detection among countries. There was no significant association between CRC stage and time since last colonoscopy. We did not find a significant reduction in CRC incidence or stage of detection in Germany (annual colonoscopic surveillance) than in countries with longer surveillance intervals (the Netherlands, with 1-2-year intervals, and Finland, with 2-3-year intervals). Overall, we did not find a significant association of the interval with CRC risk, although age, sex, mutation, and prior neoplasia were used to individually modify colonoscopy intervals. Studies are needed to develop and validate risk-adapted surveillance strategies and to identify patients who benefit from shorter surveillance intervals.

A novel role for estrogen-induced signaling in the colorectal cancer gender bias.

Colorectal cancer (CRC) is a malignancy whose incidence is increasing globally, and there is a gender difference in the increasing risk. Evidence from hormone replacement therapy studies points to a role for circulating estrogens in suppressing the development of CRC. Estrogen receptor-β has been identified as a tumor suppressor, but other actions of estrogen may also contribute to the difference in CRC incidence between men and women. The KCNQ1/KCNE3 potassium channel is regulated by estrogen in order to modulate chloride secretion during the menstrual cycle; the effect of estrogen on the colon is to promote fluid conservation during the implantation window. KCNQ1 is also a tumor suppressor in CRC, and its sustained expression has been linked to suppression of the Wnt/β-catenin signaling pathway that contributes to CRC tumor progression. KCNQ1 regulation may represent a link between the normal physiological actions of estrogen in the colon and the hormone's apparent tumor-suppressive effects in CRC development.

The Future Burden of Colorectal Cancer Among US Blacks and Whites.

Although overall colorectal cancer (CRC) incidence rates in the United States are declining, rates among younger persons (age < 55 years) are increasing, particularly among US whites. We assessed how these trends will impact the future burden (up to 2040) of CRC among US blacks and whites using an age-period-cohort model. Over the last four decades (1973 to 2014), CRC incidence rates for all ages (both sexes) have dropped by 6.6% and 33.9% in US blacks and whites, respectively. Yet we predict an upward turn in CRC cancer incidence rates over the next quarter century, particularly among US whites. The age-standardized rates of CRC were 55.4 and 43.2 per 100 000 among US blacks and whites in 2014, respectively, and are projected to be 49.5 and 43.1 in 2040, respectively. Future interventions are needed to reduce the striking differences in CRC incidence between blacks and whites.

Increased paracellular permeability of tumor-adjacent areas in 1,2-dimethylhydrazine-induced colon carcinogenesis in rats.

Objective:The morphology and functions of the proximal and distal large intestine are not the same. The incidence of colorectal cancer in these regions is also different, as tumors more often appear in the descending colon than in the ascending colon. Inflammatory bowel disease and colorectal cancer can increase transepithelial permeability, which is a sign of reduced intestinal barrier function. However, there is not enough evidence to establish a connection between the difference in colorectal cancer incidence in the proximal and distal colon and intestinal permeability or the effects of carcinogenesis on the barrier properties in various areas of the colon. The aim of the study was to assess the permeability of different segments of the large intestine according to a developed mapping methodology in healthy rats and rats with 1,2-dimethylhydrazine (DMH)-induced colon adenocarcinoma.Methods:The short circuit current, the transepithelial electrical resistance and the paracellular permeability to fluorescein of large intestine wall of male Wistar rats were examined in the Ussing chambers. The optical density of the solution from the serosa side to assess the concentration of the diffused fluorescein from mucosa to serosa was analyzed by spectrophotometry. The morphometric and histological studies were performed by optical microscopy.Results:Rats with DMH-induced colon adenocarcinomas showed elevated transepithelial electrical resistance in the areas of neoplasm development. In contrast, there was no change in the electrophysiological properties of tumor adjacent areas, however, the paracellular permeability of these areas to fluorescein was increased compared to the control rats and was characterized by sharply reduced barrier function.Conclusions:The barrier properties of the colon vary depending on tumor location. The tumors were less permeable than the intact intestinal wall and probably have a negative influence on tumor-adjacent tissues by disrupting their barrier function.

Issue Highlights

Issue Highlights

Abstract B25: Black-white differences in colorectal cancer screening and incidence over time by age and sex

Abstract Introduction: Blacks have the highest colorectal cancer (CRC) burden of any racial/ethnic group and the underlying reason for this disparity has not been fully elucidated. Continued examination of incidence in relation to screening, which is recommended for men and women beginning at age 50 years, may provide valuable insights into these disparities. The present study examined black-white differences in CRC incidence and screening patterns by age and sex over time. Methods: National Health Interview Surveys between 2000-2015 were used to estimate screening prevalence and prevalence ratios (PR) among adults 50 years and older by non-Hispanic white/black race and sex. Data from the SEER were used to estimate age-sex-specific incidence rates from 1992-2013. Results: From 2000 to 2015, CRC screening prevalence in age 50 years and older increased by 69% in whites (from 39.4% to 66.5%) and by 98% in blacks (from 31.1% to 61.4%) on a relative scale. Increases in CRC screening were evident in both men and women. During this time period, black-white differences also narrowed, such that CRC screening in blacks was 19% lower than in whites in 2000 (PR=0.81, 95%CI 0.71,0.92) but only 6% lower in 2015 (PR=0.94, 95%CI 0.88, 1.00). Absolute black-white differences in CRC incidence rates were slightly larger for men than for women (men: 3.0-6.0 versus women: 2.8-5.4 per 100,000) in people 35-49 years old, but decreased overtime in both groups. In 50-79-year-olds, absolute black-white incidence differences were larger for men prior to 2003 (men: 19.8-28.9 versus women: 28.3-33.1 per 100,000) and during 2004-2013 (men: 27.7-53.3 versus women: 20.6-38.7 per 100,000). In 35-49-year-olds, black-white incidence rate ratios (IRR) decreased overtime from 1992-2000 to 2009-2013 in both men (1.47 to 1.19) and women (1.49 to 1.17), but increased in both men (1.06 to 1.38) and women (1.15 to 1.49) for those 50 years and older. Conclusions: Black-white differences in CRC incidence in both absolute and relative terms are greatest in screening-eligible adults and have persisted in recent years whereas absolute differences in incidence in those younger than 50 are relatively small. These patterns may reflect racial gaps in screening uptake. However, disparities in CRC screening prevalence have narrowed in recent years and may portend convergence in CRC incidence rates. Note: This abstract was not presented at the conference. Citation Format: Stacey A. Fedewa, Douglas Corley, Ahmedin Jemal, Rebecca Siegel, Michael Goodman, Chyke Doubeni. Black-white differences in colorectal cancer screening and incidence over time by age and sex. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B25.