Reduce Colorectal Cancer Incidence Research Articles

Adherence to the Mediterranean diet and its protective effects against colorectal cancer: a meta-analysis of 26 studies with 2,217,404 participants.

Colorectal cancer (CRC) is a major global health concern and represents a significant public health challenge in Hungary, where it exhibits some of the highest morbidity and mortality rates in the European Union. The Mediterranean diet has been suggested to reduce the incidence of CRC, but comprehensive evidence from diverse study designs is needed to substantiate this effect. A systematic literature search was conducted in PubMed, ClinicalTrials.gov, CENTRAL, and the Web of Science to identify randomized controlled trials and human clinical trials from 2008 to 2024 to identify relevant studies. Statistical analysis was performed using the https://metaanalysisonline.com web application using a random effects model to estimate the pooled hazard rates (HRs). Forest plots, funnel plots, and Z-score plots were utilized to visualize results. We identified 15 clinical trials and 9 case-control studies, encompassing a total of 2,217,404 subjects. The pooled analysis indicated that adherence to the Mediterranean diet significantly reduced the prevalence of CRC (HR = 0.84, 95% CI = 0.78-0.91, p < 0.01). This protective effect was consistent across sexes, with HRs of 0.85 (95% CI = 0.75-0.97, p = 0.01) for males and 0.88 (95% CI = 0.79-0.99, p = 0.03) for females. Case-control studies specifically showed a substantial effect (HR = 0.51, 95% CI = 0.38-0.68, p < 0.01). Notable heterogeneity was observed across studies, yet the a priori information size was substantially below the cumulative sample size, ensuring sufficient data for reliable conclusions.The findings from this meta-analysis reinforce the protective role of the Mediterranean diet against CRC. The results of this meta-analysis will inform dietary interventions designed to mitigate CRC risk, which are conducted within the framework of the Semmelweis Study, an ongoing comprehensive cohort study at Semmelweis University, designed to explore the multifaceted causes of unhealthy aging in Hungary. These interventions aim to explore the practical application of Mediterranean dietary patterns in reducing CRC incidence among the Hungarian population.

Impact of racial disparities in follow-up and quality of colonoscopy on colorectal cancer outcomes.

The benefits of colorectal cancer (CRC) screening programs rely on completing follow-up colonoscopy when a noncolonoscopy test is abnormal and on quality of colonoscopy screening as measured by the endoscopists' adenoma detection rate. Existing data demonstrate substantially lower follow-up colonoscopy rates and adenoma detection rate for Black Americans than White Americans. However, the contributions of racial differences in follow-up colonoscopy and adenoma detection rate on CRC outcomes have not been rigorously evaluated. We used established and validated CRC-Adenoma Incidence and Mortality (CRC-AIM) model as our analysis platform, with inputs from published literature that report lower follow-up colonoscopy rates and adenoma detection rate in Black adults compared with White adults (15% and 10% lower, respectively). We simulated screening with annual fecal immunochemical test, triennial multitarget stool DNA, and colonoscopy every 10 years between ages 45 and 75 years using real-world utilization of the screening modalities vs no screening. We reported lifetime outcomes per 1000 Black adults. Elimination of Black-White disparities in follow-up colonoscopy rates would reduce CRC incidence and mortality by 5.2% and 9.3%, respectively, and improve life-years gained with screening by 3.4%. Elimination of Black-White disparities in endoscopists' adenoma detection rate would reduce CRC incidence and mortality by 9.4% and improve life-years gained by 3.7%. Elimination of both disparities would reduce CRC incidence and mortality by 14.6% and 18.7%, respectively, and improve life-years gained by 7.1%. This modeling study predicts eliminating racial differences in follow-up colonoscopy rates, and quality of screening colonoscopy would substantially reduce Black-White disparities in CRC incidence and mortality.

Endoscopic techniques for management of large colorectal polyps, strictures and leaks

The implementation of screening colonoscopy with polyp removal has significantly decreased mortality rates associated with colorectal cancer (CRC), although it remains a major cause of cancer-related deaths globally. CRC typically originates from adenomatous polyps, and increased removal of these growths has led to reduced CRC incidence and mortality. Endoscopic polypectomy techniques, including hot and cold snare polypectomy, play a pivotal role in this process. While both methods are effective for small polyps (<10 mm), recent evidence favors cold snare polypectomy due to its superior safety profile and comparable complete resection rates. Large polyps (>10 mm), particularly those with advanced features, pose increased cancer risks and often require meticulous assessment and advanced endoscopic techniques, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), for resection.This chapter also provides a practical overview of endoscopic techniques for managing colonic obstructions and pericolonic fluid collections, detailing their indications, advantages, disadvantages, and complications. The goal is to improve understanding and application in clinical practice. Additionally, we provide a summary of endoscopic closure techniques that have revolutionized the management of perforations and fistulas, offering safe and effective alternatives to surgery.

Real-world multi-target stool DNA longitudinal adherence for colorectal cancer re-screening in a large, national population.

e15633 Background: Colorectal cancer (CRC) is the fourth most diagnosed cancer, as well as the second leading cause of cancer death in the United States – with an estimated 152,810 diagnoses and 53,010 fatal cases in 2024. Regular screening and early detection can reduce CRC incidence and improve overall survival; however, recent national survey data (2021) demonstrate that only 59% of the US screen-eligible population (≥ age 45) is up to date. Home-based, non-invasive CRC screening test options, such as the multi-target stool DNA (mt-sDNA) test, have the potential to improve patient outcomes and overcome CRC screening adherence barriers at multiple levels. Given that the recommended interval for mt-sDNA is three years, a better understanding of use in repeat users is warranted. We evaluated the effective rescreen rate of previous mt-sDNA test users. Methods: In this retrospective cohort study, we included patients between the ages of 45 and 75 years who were shipped an mt-sDNA test kit between January 1st – December 31st, 2023, and had previously completed mt-sDNA screening with a negative result &gt; 2.5 years prior. Our primary variable of interest was mt-sDNA completion rate on repeat testing, defined as kit receipt with a valid result within 120 days of the shipment date. Regression analysis was performed to determine baseline characteristics associated with repeat test completion rate. Results: During the analysis period, a total of 481,748 patients who met the inclusion criteria received an mt-sDNA kit. The majority of the cohort was female (61.4%) and between the ages of 65-75 years (50.9%). Overall repeat test completion rate was 83.6%, with the average time to kit return being 18.9 days. Completion rates were similar between males (83.8%) and females (83.6%), and patients receiving included navigation support via mobile phones demonstrated the shortest average time to kit return (18.7 days). Completion rates increased concordantly with patient age: 81.6%, (45-49 years), 82.2% (50-64 years), and 85% (65-75 years). For first-time rescreen participants (2nd lifetime mt-sDNA test), the completion rate was 83.1%. For second-time rescreen participants (3rd lifetime mt-sDNA test), the completion rate was even higher at 93.6%. Logistic regression analyses revealed that patients re-screening for a second-time were three times more likely to return the mt-sDNA kit for CRC screening (OR = 3.118; p &lt; 0.001). Conclusions: Data from this large, retrospective cohort study revealed that repeat CRC screening with the mt-sDNA test is associated with high adherence to triennial follow-up among participants. suggesting a high-level of perceived patient confidence in repeat performance of the mt-sDNA test. These novel data provide relevant insights regarding strong patient willingness to continue with home-based, non-invasive mt-sDNA testing over multiple cycles of average-risk CRC screening.

Duration of risk reduction in colorectal cancer incidence and mortality after a complete colonoscopy in Ontario, Canada: a population-based cohort study

Colorectal cancer guidelines recommend screening colonoscopy every 10 years after a negative procedure. If risk reduction extends past 10 years, the recommended interval could be extended, reducing the burden on the individual and health-care system. We aimed to estimate the duration that patients remain at reduced risk of colorectal cancer incidence and mortality after a complete colonoscopy. We did a population-based cohort study of individuals aged 50-65 years between Jan 1, 1994, to Dec 31, 2017. We excluded individuals with previous exposure to colonoscopy or colorectal surgery, those previously diagnosed with colorectal cancer, or a history of hereditary or other bowel disorders. We followed up participants until Dec 31, 2018, and identified all colonoscopies performed in this time period. We used a 9-level time-varying measure of exposure, capturing time since last complete colonoscopy (no complete colonoscopy, ≤5 years, >5-10 years, >10-15 years, and >15 years) and whether an intervention was performed (biopsy or polypectomy). A Cox proportional hazards regression model adjusting for age, sex, comorbidity, residential income quintile, and immigration status was used to estimate the association between exposure to a complete colonoscopy and colorectal cancer incidence and mortality. 5 298 033 individuals (2 609 060 [49·2%] female and 2 688 973 [50·8%] male; no data on ethnicity were available) were included in the cohort, with a median follow-up of 12·56 years (IQR 6·26-20·13). 90 532 (1·7%) individuals were diagnosed with colorectal cancer and 44 088 (0·8%) died from colorectal cancer. Compared with those who did not have a colonoscopy, the risk of colorectal cancer in those who had a complete negative colonoscopy was reduced at all timepoints, including when the procedure occurred more than 15 years earlier (hazard ratio [HR] 0·62 [95% CI 0·51-0·77] for female individuals and 0·57 [0·46-0·70] for male individuals. A similar finding was observed for colorectal cancer mortality, with lower risk at all timepoints, including when the procedure occurred more than 15 years earlier (HR 0·64 [95% CI 0·49-0·83] for female participants and 0·65 [0·50-0·83] for male participants). Those who had a colonoscopy with intervention had a significantly lower colorectal cancer incidence than those who did not undergo colonoscopy if the procedure occurred within 10 years for females (HR 0·70 [95% CI 0·63-0·77]) and up to 15 years for males (0·62 [(0·53-0·72]). Compared with those who do not receive colonoscopy, individuals who have a negative colonoscopy result remain at lower risk for colorectal cancer incidence and mortality more than 15 years after the procedure. The current recommendation of repeat screening at 10 years in these individuals should be reassessed. Canadian Institutes of Health Research.

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.

Utilization of colorectal cancer screening tests across European countries: a cross-sectional analysis of the European health interview survey 2018–2020

Colorectal cancer (CRC) screening has been shown to reduce CRC incidence and mortality, and most European countries have started to implement CRC screening programs in the past 20 years. Consequently, this study aimed to estimate the utilization of fecal tests and colonoscopy, as well as investigate factors associated with their utilization based on specific screening program characteristics in European countries. We analyzed data from the European Health Interview Survey 2018-2020 to determine the utilization of fecal tests [guaiac-based fecal occult blood test (gFOBT) or fecal immunochemical test (FIT)] within the preceding 2 years or colonoscopy within the preceding 10 years among people aged 50-74 years, based on the type of screening offered in each country. Using multivariable logistic regression and sub-group meta-analysis, factors associated with screening use were determined. The analyses included data from 129,750 respondents across 29 European countries, with participant counts ranging from 1511 individuals in Iceland to 11,755 individuals in Germany. Unit response rates ranged from 22% to 88%. The use of either test was highest among countries with fully rolled-out programs with fecal tests [from 37.7% (867/2379) in Croatia to 74.9% (2321/3085) in Denmark] and in countries offering colonoscopy as an alternative screening method [from 26.2% (854/3329) in Greece to 75.4% (1192/1760) in Luxembourg]. We observed the lowest utilization of either test in countries with no program or small-scale programs [6.3% (195/3179) in Bulgaria to 34.2% (722/2144) in Latvia]. Across all types of screening offers, younger age, being without a partner, low education, rural residence, and living in large households were associated with lower utilization, as were poor lifestyle scores and prolonged periods without physician consultation. Our findings point to large disparities and much room for improvement in CRC screening offers and utilization across Europe. There was no funding source for this study.

Colorectal Cancer Screening by Fecal Immunochemical Tests (FIT): Considerations on Sampling and Markers (Hb and Hb/Hp Complex) of Fecal Occult Blood (FOB).

Formal demonstration of the efficacy of colorectal cancer (CRC) screening by fecal immunochemical tests (FITs) in reducing CRC incidence and mortality is still missing. The aim of this study was to analyze the impact of sampling and FIT marker in the recently implemented CRC screening program in Finland. Because only the index test [FIT hemoglobin (Hb)]-positive subjects are verified by the reference test (colonoscopy), the new screening program is subject to verification bias that precludes estimating the diagnostic accuracy (DA) indicators. A previously published study (5) with 100% biopsy verification of colonoscopy referral subjects (called validation cohort, n=300) was used to derive these missing DA estimates. Two points of concern were addressed: i) only one-day sample tested, and ii) only the Hb component (but not Hb/Hp complex) was analyzed by FIT. The estimated DA of one-sample testing for Hb in the screening setting had a very low sensitivity (SE) (12.5%; 95%CI=12.3-12.7) for adenomas, with AUC=0.560 (for CRC, AUC=0.950). Testing three samples for Hb improved SE to 19.4% (95%CI=19.1-19.7%) but had little effect on overall DA (AUC=0.590). For adenomas, one-sample testing for Hb and Hb/Hp complex provided higher SE than three-sample testing for Hb (SE 20.6%; 95%CI=20.3-21.0), and the best SE was reached when two samples were tested for Hb and Hb/Hp complex (SE 47.5%; 95%CI=46.9-48.1%) (AUC=0.730). The strategy of the current CRC screening could be significantly improved by testing two consecutive samples by Hb and Hb/Hp complex, instead of stand-alone Hb testing of one sample.

Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy

Colorectal cancer (CRC) screening is highly effective but underused. Blood-based biomarkers (liquid biopsy) could improve screening participation. Using our established Markov model, screening every 3 years with a blood-based test that meets minimum Centers for Medicare & Medicaid Services' thresholds (CMSmin) (CRC sensitivity 74%, specificity 90%) was compared with established alternatives. Test attributes were varied in sensitivity analyses. CMSmin reduced CRC incidence by 40% and CRC mortality by 52% vs no screening. These reductions were less profound than the 68%-79% and 73%-81%, respectively, achieved with multi-target stool DNA (Cologuard; Exact Sciences) every 3 years, annual fecal immunochemical testing (FIT), or colonoscopy every 10 years. Assuming the same cost as multi-target stool DNA, CMSmin cost $28,500/quality-adjusted life-year gained vs no screening, but FIT, colonoscopy, and multi-target stool DNA were less costly and more effective. CMSmin would match FIT's clinical outcomes if it achieved 1.4- to 1.8-fold FIT's participation rate. Advanced precancerous lesion (APL) sensitivity was a key determinant of a test's effectiveness. A paradigm-changing blood-based test (sensitivity >90% for CRC and 80% for APL; 90% specificity; cost ≤$120-$140) would be cost-effective vs FIT at comparable participation. CMSmin could contribute to CRC control by achieving screening in those who will not use established methods. Substituting blood-based testing for established effective CRC screening methods will require higher CRC and APL sensitivities that deliver programmatic benefits matching those of FIT. High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers. APL detection should not be penalized by a definition of test specificity that focuses on CRC only.

Abstract 7305: Chemoprevention of colorectal cancer: Role of trace minerals in conjunction with calcium

Abstract Background: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. CRC usually develops from adenomas (CRC precursors) after a long latency period. Prevention is crucial in reducing CRC incidence and progression to cancer. Among several prevention options, calcium has been a widely considered chemo-preventative agent. Aims: Calcium plays a vital role in the regulation of epithelial cell differentiation, which is essential for epithelial growth control. Epidemiological studies have demonstrated that adequate calcium intake is crucial for protection against colonic polyp formation and colorectal cancer. However, recent interventional trials with calcium have had only modest and mixed results, and the question is how to improve efficacy. One potential strategy is to use calcium in combination with additional minerals and trace elements. Results: Our preclinical studies employing monolayer cultures with CRC cell lines and colon organoids cultures from colon polyps have shown that a calcium-rich mineral combination derived from fossilized red algae (Aquamin) is more effective than calcium alone in inducing differentiation, suppressing growth and upregulation of calcium-sensing receptor. When colonic adenomas in culture were subjected to differential proteomic analysis, Aquamin upregulated several proteins involved in proliferation suppression, DNA mismatch repair and inducing differentiation, and apoptosis. Two long-term mouse studies have demonstrated that Aquamin is more effective in suppressing polyp &amp; CRC incidence compared to calcium alone. Based on these findings, we conducted a 90-day FDA-approved trial (a pilot study with ten subjects per arm) comparing the two interventions in human subjects at risk for CRC. Results showed that Aquamin treatment reduced proliferation and increased cell differentiation observed by immunohistochemistry. Proteomic analysis also revealed that the minerals upregulated several proteins related to growth suppression, inducing differentiation and those contributing to cell-cell and cell-matrix adhesion functions and downregulated proteins involved in proliferation and nucleic acid metabolism. Conclusion: These results provide convincing evidence that a multi-mineral combination derived from red algae can provide benefits in preventing CRC that are not seen with calcium alone. Further studies, such as a polyp-prevention trial in human subjects, are warranted to advance these CRC prevention efforts. Citation Format: Isabelle Harber, Shannon McClintock, James Varani, Muhammad N. Aslam. Chemoprevention of colorectal cancer: Role of trace minerals in conjunction with calcium [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 7305.

Establishment of standards for the referral of large nonpedunculated colorectal polyps: an international expert consensus using a modified Delphi process

Resection of colorectal polyps has been shown to decrease the incidence and mortality of colorectal cancer. Large nonpedunculated colorectal polyps are often referred to expert centers for endoscopic resection, which requires relevant information to be conveyed to the therapeutic endoscopist to allow for triage and planning of resection technique. The primary objective of this study was to establish minimum expected standards for the referral of large non-pedunculated colonic polyps for potential endoscopic resection. A Delphi method was used to establish consensus on minimum expected standards for the referral of large colorectal polyps among a panel of international endoscopy experts. The expert panel was recruited through purposive sampling, and 3 rounds of surveys were conducted to achieve consensus. Quantitative and qualitative data were analyzed for each round. A total of 24 international experts from diverse continents participated in the Delphi study, resulting in consensus on 19 statements related to the referral of large colorectal polyps. The identified factors, including patient demographic characteristics, relevant medications, lesion factors, photodocumentation, and the presence of a tattoo, were deemed important for conveying the necessary information to therapeutic endoscopists. The mean scores for the statements, which were scored on a scale of 1 to 10, ranged from 7.04 to 9.29, with high percentages of experts considering most statements as a very high priority. Subgroup analysis according to continent revealed some variations in consensus rates among experts from different regions. The identified consensus statements can aid in improving the triage and planning of resection techniques for large colorectal polyps, ultimately contributing to the reduction of colorectal cancer incidence and mortality.

Colorectal cancer screening at age 45 years in Israel: Cost-effectiveness and global implications.

Colorectal cancer (CRC) incidence at ages <50years is increasing worldwide. Screening initiation was lowered to 45years in the United States. The cost-effectiveness of initiating CRC screening at 45years in Israel was assessed with the aim of informing national policy and addressing internationally relevant questions. A validated CRC screening model was calibrated to Israeli data and examined annual fecal immunochemical testing (FIT) or colonoscopy every 10years from 45 to 74 years (FIT45-74 or Colo45-74) versus from 50 to 74 years (FIT50-74 or Colo50-74). The addition of a fourth colonoscopy at 75years was explored, subanalyses were performed by sex/ethnicity, and resource demands were estimated. FIT50-74 and Colo50-74 reduced CRC incidence by 57% and 70% and mortality by 70% and 77%, respectively, versus no screening, with greater absolute impact in Jews/Other versus Arabs but comparable relative impact. FIT45-74 further reduced CRC incidence and mortality by an absolute 3% and 2%, respectively. With Colo45-74 versus Colo50-74, CRC cases and deaths increased slightly as three colonoscopies per lifetime shifted to 5years earlier but mean quality-adjusted life-years gained (QALYGs) per person increased. FIT45-74 and Colo45-74 cost 23,800-53,900 new Israeli shekels (NIS)/QALYG and 110,600-162,700 NIS/QALYG, with the lowest and highest values among Jewish/Other men and Arab women, respectively. A fourth lifetime colonoscopy cost 48,700 NIS/QALYG. Lowering FIT initiation to 45years with modest participation required 19,300 additional colonoscopies in the first 3years. Beginning CRC screening at 45years in Israel is projected to yield modest clinical benefits at acceptable costs per QALYG. Despite different estimates by sex/ethnicity, a uniform national policy is favored. These findings can inform Israeli guidelines and serve as a case study internationally.

Prevalence of neoplasia at colonoscopy among testicular cancer survivors treated with platinum-based chemotherapy.

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have an increased risk of colorectal cancer (CRC). We determined the yield of colonoscopy in TCS to assess its potential in reducing CRC incidence and mortality. We conducted a colonoscopy screening study among TCS in four Dutch hospitals to assess the yield of colorectal neoplasia. Neoplasia was defined as adenomas, serrated polyps (SPs), advanced adenomas (AAs: ≥10 mm diameter, high-grade dysplasia or ≥25% villous component), advanced serrated polyps (ASPs: ≥10 mm diameter or dysplasia) or CRC. Advanced neoplasia (AN) was defined as AA, ASP or CRC. Colonoscopy yield was compared to average-risk American males who underwent screening colonoscopy (n = 24,193) using a propensity score matched analysis, adjusted for age, smoking status, alcohol consumption and body mass index. A total of 137 TCS underwent colonoscopy. Median age was 50 years among TCS (IQR 43-57) vs 55 years (IQR 51-62) among American controls. A total of 126 TCS were matched to 602 controls. The prevalence of AN was higher in TCS than in controls (8.7% vs 1.7%; P = .0002). Nonadvanced adenomas and SPs were detected in 45.2% of TCS vs 5.5% of controls (P < .0001). No lesions were detected in 46.0% of TCS vs 92.9% of controls (P < .0001). TCS treated with platinum-based chemotherapy have a higher prevalence of neoplasia and AN than matched controls. These results support our hypothesis that platinum-based chemotherapy increases the risk of colorectal neoplasia in TCS. Cost-effectiveness studies are warranted to ascertain the threshold of AN prevalence that justifies the recommendation of colonoscopy for TCS.

Abstract A138: Impact of racial disparities in follow-up colonoscopy for abnormal stool-screening test results on colorectal cancer incidence and mortality: A simulation modeling analysis

Abstract Introduction: The benefits of colorectal cancer (CRC) screening programs for average-risk adults rely on completion of follow-up colonoscopy (FU-Col) after a positive result from either the stool-based fecal immunochemical test (FIT) or multi-target stool DNA (mt-sDNA) test. Existing data demonstrate significantly lower rates of FU-Col for Black Americans than White Americans. However, the contribution of differential FU-Col rates on disparate CRC outcomes among Black and White Americans has not been rigorously evaluated. Methods: We used the CRC-Adenoma Incidence and Mortality (CRC-AIM) model as our analysis platform, with inputs from published literature that report Black adults are approximately 15% less likely to complete FU-Col compared to White adults. CRC-AIM was validated against United Kingdom Flexible Sigmoidoscopy Screening Trial and three National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network (CISNET) CRC models. We simulated screening with annual FIT and triennial mt-sDNA between ages 45 and 75 versus no screening. We considered two scenarios that assumed perfect adherence to FIT/mt-sDNA screening: 1) FU-Col rates for Black adults are 15% lower than those for White adults; 2) Black adults have the same FU-Col rates as White adults. In a secondary analysis, we considered real-world adherence to FIT (43%) and mt-sDNA (66%) and reran these two scenarios. Lifetime outcomes per 1,000 individuals were reported. Results: Assuming perfect adherence to FIT/mt-sDNA screening and 15% lower FU-Col rates, estimated life-year gains (LYG) from annual FIT and triennial mt-sDNA screening strategies compared to no screening was 227 and 239 per 1,000 individuals, respectively. If Black adults had the same FU-Col rates as White adults, the LYG would increase to 243 and 256 for FIT and mt-sDNA screening, respectively, which corresponds to a 7% improvement in LYG. Furthermore, elimination of racial disparities in FU-Col rates would reduce CRC incidence by 8% and 9% for FIT and mt-sDNA screening, respectively and reduce CRC mortality by 10% for both FIT and mt-sDNA screening. Secondary analysis shows that eliminating disparities in FU-Col would lead to 9-11% improvement in LYGs, 5-9% improvement in CRC incidence, and 7-11% improvement in CRC mortality for Black adults considering the real-world adherence to FIT/mt-sDNA screening. Conclusions: Data from this novel simulation modeling study that accounts for differences in FU-Col rates between Black and White Americans suggest that focused efforts to eliminate this gap would improve the anticipated LYG, CRC incidence, and CRC mortality benefits associated with stool-based CRC screening by over 7%, 8%, and 10%, respectively. Further investigation of this under-appreciated contributor to established racial disparities in CRC control may lead to innovative solutions for improving health equity. Citation Format: Oguz Alagoz, A. Mark Fendrick, Vahab Vahdat, Chris Estes, A. Burak Ozbay, Travelle Ellis, Paul J. Limburg, Durado Brooks. Impact of racial disparities in follow-up colonoscopy for abnormal stool-screening test results on colorectal cancer incidence and mortality: A simulation modeling analysis [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A138.

Probiotics intervention in colorectal cancer: From traditional approaches to novel strategies.

The intestine harbors a large population of microorganisms that interact with epithelial cells to maintain host healthy physiological status. These intestinal microbiota engage in the fermentation of non-digestible nutrients and produce beneficial metabolites to regulate host homeostasis, metabolism, and immune response. The disruption of microbiota, known as dysbiosis, has been implicated in many intestinal diseases, including colorectal cancer (CRC). As the third most common cancer and the second leading cause of cancer-related death worldwide, CRC poses a significant health burden. There is an urgent need for novel interventions to reduce CRC incidence and improve clinical outcomes. Modulating the intestinal microbiota has emerged as a promising approach for CRC prevention and treatment. Current research efforts in CRC probiotics primarily focus on reducing the incidence of CRC, alleviating treatment-related side effects, and potentiating the efficacy of anticancer therapy, which is the key to successful translation to clinical practice. This paper aims to review the traditional probiotics and new interventions, such as next-generation probiotics and postbiotics, in the context of CRC. The underlying mechanisms of probiotic anti-cancer effects are also discussed, including the restoration of microbial composition, reinforcement of gut barrier integrity, induction of cancer cell apoptosis, inactivation of carcinogens, and modulation of host immune response. This paper further evaluates the novel strategy of probiotics as an adjuvant therapy in boosting the efficacy of chemotherapy and immunotherapy. Despite all the promising findings presented in studies, the evaluation of potential risks, optimization of delivery methods, and consideration of intra-patient variability of gut microbial baseline must be thoroughly interpreted before bench-to-bedside translation.

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.

Reduction in colorectal cancer incidence by screening endoscopy.

Colorectal cancer (CRC) incidence rates decreased by up to 50% in older age groups in the USA in the era of the widespread uptake of screening colonoscopy, despite adverse trends in CRC risk factors and increasing CRC incidence at younger ages. However, reported first results from a randomized trial, the NordICC study, suggested rather modest effects of screening colonoscopy. As outlined in this Perspective, the apparent discrepancy between real-world and trial evidence could be explained by strong attenuation of effect estimates from screening endoscopy trials by several factors, including limited screening adherence, widespread uptake of colonoscopy outside the screening offers and the inclusion of prevalent, non-preventable CRC cases in reported numbers of incident cases. Alternative interpretations of screening endoscopy trial results accounting for prevalence bias are in line with trends in CRC incidence reduction in countries offering CRC screening, and should encourage more widespread implementation and uptake of effective CRC screening.

Colorectal cancer screening-what does the recent NordICC trial mean for the U.S. population?

The incidence of colorectal cancer (CRC) has declined over time, though it remains a significant cause of morbidity and mortality in the U.S. It has the third highest incidence in incidence among all cancers and is the second leading cause of cancer death in both men and women. Screening reduces the incidence and mortality from CRC. There are several modalities for CRC screening, but the most common ones are a choice between a non-invasive stool-based test, such as fecal immunochemical testing (FIT) or an invasive endoscopic modality, such as colonoscopy. In the U.S. colonoscopy is the predominant CRC screening modality, with observational studies reporting large reductions in CRC incidence and mortality. Recently, a large randomized controlled trial (RCT) on effectiveness of colonoscopy reported smaller than expected reduction in CRC incidence and no reduction in CRC mortality with colonoscopy screening. Explanations of the lower than expected benefit include low uptake of colonoscopy, short follow-up for mortality endpoints and quality indicators (QIs) for some of the endoscopists participating in the screening colonoscopies. The findings of the study need to be taken in context with other literature on effectiveness of colonoscopy, with the overall message of reassuring patients of the benefits of screening, and colonoscopy. Here, we discuss the latest evidence on colonoscopy screening and it in the context of other screening modalities and the landscape.

Genetically predicted thyroid function and risk of colorectal cancer: a bidirectional Mendelian randomization study.

Observational studies have reported an association between thyroid function and colorectal cancer (CRC), with conflicting results. Elucidating the causal relationship between thyroid function and CRC facilitates the development of new preventive strategies to reduce CRC incidence. We applied a two-sample Mendelian randomization (MR) method to evaluate the causal relationship between five thyroid-related indexes, including hyperthyroidism, hypothyroidism, thyroid stimulating hormone (TSH), free thyroxine (FT4) and basal metabolic rate (BMR), and CRC. Genome-wide association study statistics for thyroid-related phenotypes were obtained from the ThyroidOmics consortium, and summary statistics for genetic associations with CRC were obtained from the FinnGen consortium. We set a series of criteria to screen single nucleotide polymorphisms (SNPs) as instrumental variables and then performed bidirectional MR analysis, stratified analysis and extensive sensitivity analysis. Multiplicative random-effects inverse variance weighted was the primary analysis method, supplemented by weighted median and MR-Egger. We identified 12 SNPs for hyperthyroidism, 10 SNPs for hypothyroidism, 41 SNPs for TSH, 18 SNPs for FT4, and 556 SNPs for BMR. Genetically predicted hyperthyroidism, hypothyroidism, TSH, and FT4 were not associated with CRC risk (all P > 0.05). Sensitivity analysis revealed no heterogeneity or pleiotropy. Genetically predicted BMR was significantly associated with increased CRC risk after removing outlier (OR = 1.30, P = 0.0029). Stratified analysis showed that BMR was significantly associated with colon cancer (OR = 1.33, P = 0.0074) but not rectal cancer. In the reverse analysis, there was no evidence of an effect of CRC on thyroid function (all P > 0.05). Our bidirectional MR analysis provides new insights into the relationship between thyroid function and CRC. CRC prevention may benefit from enhanced screening of high BMR populations.

Loss of Pkd1 limits susceptibility to colitis and colorectal cancer

Colorectal cancer (CRC) is one of the most common cancers, with an annual incidence of ~135,000 in the US, associated with ~50,000 deaths. Autosomal dominant polycystic kidney disease (ADPKD), associated with mutations disabling the PKD1 gene, affects as many as 1 in 1000. Intriguingly, some studies have suggested that individuals with germline mutations in PKD1 have reduced incidence of CRC, suggesting a genetic modifier function. Using mouse models, we here establish that loss of Pkd1 greatly reduces CRC incidence and tumor growth induced by loss of the tumor suppressor Apc. Growth of Pkd1−/−;Apc−/− organoids was reduced relative to Apc−/− organoids, indicating a cancer cell-intrinsic activity, even though Pkd1 loss enhanced activity of pro-oncogenic signaling pathways. Notably, Pkd1 loss increased colon barrier function, with Pkd1-deficient animals resistant to DSS-induced colitis, associated with upregulation of claudins that decrease permeability, and reduced T cell infiltration. Notably, Pkd1 loss caused greater sensitivity to activation of CFTR, a tumor suppressor in CRC, paralleling signaling relations in ADPKD. Overall, these data and other data suggest germline and somatic mutations in PKD1 may influence incidence, presentation, and treatment response in human CRC and other pathologies involving the colon.