Family History Of Colorectal Cancer Research Articles

P453 Surveillance for colorectal dysplasia and neoplasia in Latin American patients with Ulcerative Colitis

Abstract Background colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) has worse prognostic features and a higher mortality rate compared to sporadic CRC. Screening colonoscopy is therefore an important tool to consider in this population. The aim of this study is to describe the findings of endoscopic surveillance of CRC in patients with IBD using the technology available in Latin American countries. Methods Descriptive, multicentre, cross-sectional, descriptive study conducted in multiple Latin American countries in patients with ulcerative colitis (UC) more than 8 years after diagnosis and ulcerative colitis with primary sclerosing cholangitis regardless of the time of diagnosis of colitis. Surveillance colonoscopies were performed according to the availability of technology in each country. Results 78 subjects, 50% women, from 5 countries (Colombia, Costa Rica, Peru, Ecuador, and Dominican Republic), with mean age 47.9 (range 20.01-89.71; SD 151.4) years, mean age at disease diagnosis of 34.7 (range 8.52-80.9; SD 14.08) years, and mean time of disease of 12.8 (range 4.6-56.8; SD 8.9) years. 57.7% (45/78) with extensive colitis, 8.9% (7/78) with a family history of colorectal cancer. 52.6% (41/78) on biologic therapy. 24.4% (19/78) current use of Azathioprine. 9% (7/78) of corticosteroids. 70.5% (55/78) oral mesalazine. In 5.1% it was used white light, 1.3% high resolution white light, 76.9% digital chromoendoscopy and 16.7% chromoendoscopy with staining. In those with digital chromoendoscopy, NBI was used in 38.3% (28/73), 37% (27/73) LCI/BLI, and 24.6% (14/73) I-Scan. It was found pseudopolyps in 50% (39/78), and 11.5% (9/78) stenosis. 7.7% (6/78) had a history of previous dysplasia. Regarding the Paris classification modified by SCENIC consensus, 28.2% (22/78) found 0-I lesions, 16 subjects were 0-I s, and 6 subjects 0-Ip. 5 subjects had 0-II lesions, of which 4 subjects in 0-IIa, and 1 in 0-IIc. 1 subject had lesion type 0-III. 1 subject had mixed lesions (0-IIa+0-IIc), 6.4% (5/78) lesion with ulceration, 10.2% (8/78) with disruption of lesion borders, with KUDO classification, Kudo III, 5.1 (4/78) Kudo IV and 3.8% (3/78) Kudo V. Endoscopic resectability was possible in all lesions. Histological findings were: (11/78) low grade dysplasia, (1/78) high grade dysplasia and (3/78) adenocarcinoma. As for the presence of dysplasia not visible in white light in random biopsies, it was only detected in (2/78). Conclusion in this first Latin American study, endoscopic techniques with digital chromoendoscopy with targeted biopsies were preferred, most were endoscopically visible and resectable lesions suggesting that the yield of targeted biopsies is superior to random biopsies.

N32 Implementation of chromoendoscopy in colorectal cancer screening in patients with Inflammatory Bowel Disease

Abstract Background Patients with inflammatory bowel disease (IBD) have a higher risk of colorectal cancer (CRC), so we must implement the best available endoscopic technique to detect it early, decreasing the risk of CRC and death. There is low adherence to CRC screening by chromoendoscopy with dye in patients with IBD, despite the fact that national and international clinical practice guidelines consider this technique of choice based on the available evidence. Description Of The Initiative The standardization of a screening procedure, based on the evidence of endoscopy, allows any member of the team, doctor or nurse, to detect the need for the indication, improving screening in terms of follow-up interval and technique. Likewise, the inflammatory nurse will have to know the technique to be able to inform the patient and improve their adherence, preparation and resolve doubts. The main aim is early detection of dysplasia and CRC. The side aims are: ▪ To improve the implementation of chromoendoscopy as a technique for CRC screening. ▪ Improve patient adherence to colonoscopy. Methods The development of an endoscopic follow-up procedure according to risk factors in patients with ulcerative colitis and colonic Crohn's disease, in which chromoendoscopy is the technique of choice. The technique in our center is with 0.4% carmine indigo diffusion with catheter-diffuser, but it is possible to adapt other alternatives according to availability. The procedure establishes the follow-up interval at 1, 3 or 5 years depending on the low, medium or high risk, respectively, depending on the activity, extent and duration of the disease, presence of stenosis and pseudopolyps, primary sclerosing cholangitis and/or family history of CRC. Results In our center, 100% of screenings are performed by chromoendoscopy with dye, by a single expert endoscopist, scheduled with a longer examination time than a conventional colonoscopy and with optimization of bowel preparation. Conclusion CRC screening of patients with IBD should preferably be performed with chromoendoscopy with dye, establishing follow-up intervals depending on known risk factors, both clinical, endoscopic and histological, and this indication should be standardized in a procedure that is known to all members of the team.

The impact of endoscopist performance and patient factors on distal adenoma detection and colorectal cancer incidence

BackgroundHigh quality endoscopy is key for detecting and removing precursor lesions to colorectal cancer (CRC). Adenoma detection rates (ADRs) measure endoscopist performance. Improving other components of examinations could increase adenoma detection.AimsTo investigate how endoscopist performance at flexible sigmoidoscopy (FS) affects adenoma detection and CRC incidence.MethodsAmong 34,139 participants receiving FS screening by the main endoscopist at one of 13 centres in the UK FS Screening Trial, median follow-up was 17 years. Factors examined included family history of CRC, bowel preparation quality, insertion and withdrawal time, bowel segment reached, patient pain and ADR. Odds ratios (OR) for distal adenoma detection were estimated by logistic regression. Hazard ratios (HR) for distal CRC incidence were estimated by Cox regression.ResultsAt screening, 4,104 participants had distal adenomas detected and 168 participants developed distal CRC during follow-up. In multivariable models, a family history of CRC (yes vs. no: OR 1.40, 95%CI 1.21–1.62), good or adequate bowel preparation quality (vs. excellent: OR 0.84, 95%CI 0.74–0.95; OR 0.56, 95%CI 0.49–0.65, respectively) and longer insertion and withdrawal times (≥ 4.00 vs. < 2.00 min: OR 1.96, 95%CI 1.68–2.29; OR 32.79, 95%CI 28.22–38.11, respectively) were associated with adenoma detection. Being screened by endoscopists with low or intermediate ADRs, compared to high ADRs, was positively associated with CRC incidence (multivariable: HR 4.71, 95%CI 2.65–8.38; HR 2.16, 95%CI 1.22–3.81, respectively).ConclusionsBowel preparation quality and longer insertion and withdrawal time are key for improving distal adenoma detection. Higher ADRs were associated with a lower risk of distal CRC.

Genetic testing of Japanese patients with serrated polyposis syndrome: A multicentric study.

75 Background: Serrated polyposis syndrome (SPS) is a rare condition associated with an increased risk of colorectal cancer. Previous studies have identified germline truncating variants of the RNF43; however, patients harboring these variants comprise a small part of those with SPS, in most of whom the causative gene remains unknown. To date, no study has described the genetic features of Japanese patients with SPS. The present study aimed to identify candidate causative genes of SPS in Japanese patients. Methods: Captures for equal to or more than 55 gene regions were performed using Agilent HaloPlex or Ion AmpliSeq technologies in SPS patients enrolled in The Study Group for Establishment of Diagnosis of Hereditary Gastrointestinal Tract Cancer Syndromes Based on a Next-Generation Sequencing Technology (SGHGCS). Whole exome sequencing of tumor tissue was performed whenever a candidate gene was identified. Results: Eleven patients (four males, seven females) were enrolled. Of these, nine had a history of colorectal cancer; four had a family history of colorectal cancer; and two had a family history of polyposis. Genetic testing identified two variants of VUS, POLD1 c.670C&gt;T (p.R224C) and BRCA2 c.4169T&gt;G (p.L1390W). Additionally, a nonsense variant, BUB1:c.1543G&gt;T p.Gly515Ter was deemed likely to be pathogenic. The patient with the BUB1 variant was 47-year-old female with transverse colon cancer with more than 50 serrated polyps. She was a non-smoker. The variants detected in the transverse colon cancer did not include the canonical variants in common colorectal cancer, such as APC, KRAS or TP53 and were mostly transition substitutions (C&gt;T). Conclusions: BUB1 was identified as a novel candidate causative gene of SPS in a patient with SPS with no smoking habit. These findings will hopefully contribute to our understanding of the genetic basis of SPS.

Identification of taxonomic changes in the fecal bacteriome associated with colorectal polyps and cancer: potential biomarkers for early diagnosis.

Colorectal cancer (CRC) commonly arises in individuals with premalignant colon lesions known as polyps, with both conditions being influenced by gut microbiota. Host-related factors and inherent characteristics of polyps and tumors may contribute to microbiome variability, potentially acting as confounding factors in the discovery of taxonomic biomarkers for both conditions. In this study we employed shotgun metagenomics to analyze the taxonomic diversity of bacteria present in fecal samples of 90 clinical subjects (comprising 30 CRC patients, 30 with polyps and 30 controls). Our findings revealed a decrease in taxonomic richness among individuals with polyps and CRC, with significant dissimilarities observed among the study groups. We identified significant alterations in the abundance of specific taxa associated with polyps (Streptococcaceae, Lachnoclostridium, and Ralstonia) and CRC (Lactobacillales, Clostridiaceae, Desulfovibrio, SFB, Ruminococcus, and Faecalibacterium). Clostridiaceae exhibited significantly lower abundance in the early stages of CRC. Additionally, our study revealed a positive co-occurrence among underrepresented genera in CRC, while demonstrating a negative co-occurrence between Faecalibacterium and Desulfovibrio, suggesting potential antagonistic relationships. Moreover, we observed variations in taxonomic richness and/or abundance within the polyp and CRC bacteriome linked to polyp size, tumor stage, dyslipidemia, diabetes with metformin use, sex, age, and family history of CRC. These findings provide potential new biomarkers to enhance early CRC diagnosis while also demonstrating how intrinsic host factors contribute to establishing a heterogeneous microbiome in patients with CRC and polyps.

Ulcerative colitis complicated with hypermucinous dysplasia.

Patients with ulcerative colitis are at increased risk for colorectal neoplasia compared to the general population. The risk factors include family history of colorectal cancer, wide extent of colitis, disease duration, cumulative inflammatory burden, and primary sclerosing cholangitis. Here, we report a case of colorectal neoplasia developed in a patient with ulcerative colitis.

Colorectal polyps risk factors: A case–control study in ABIDJAN (CÔTE D’IVOIRE)

Abstract Background and Objectives: Adenomas and certain serrated polyps have the potential to develop into colorectal cancer (CRC). Despite barriers limiting routine screening for CRCs in Côte d’Ivoire, it is important to focus on the risk factors for colorectal (CR) polyps. To facilitate the identification of individuals to prioritize for CRC screening, this study aimed to determine the risk factors of CR polyps in a hospital setting in Abidjan. Materials and Methods: From January 1st, 2023, to July 31st, 2023, a prospective analytical multicenter case–control study was conducted in four hospitals in Abidjan. Patients diagnosed with CR polyps (cases) were compared to those without polyps (controls), matched for age and gender at a 1:1 ratio. Logistic regression was employed to determine factors associated with the discovery of CR polyps. Results: Thirty-three cases were matched to 33 controls [age (P = 0.97), gender (P = 0.80), recruitment site (P = 1.00), indication for colonoscopy (P = 0.93)]. Adenomatous polyps represented 68.3% (n = 28) of cases. In univariate analysis, factors associated with CR polyps were body mass index (P = 0.004), personal or family history of CRC (P = 0.004) and/or CR polyps (P = 0.007), and consumption of red meat (P &lt; 0.001). After multivariate analysis, only red meat consumption was statistically associated with CR polyps (P = 0.02) [odds ratio (OR) = 17.0 (1.5–189.3)]. Alcohol and tobacco were not statistically associated with the presence of CR polyps either in univariate analysis [alcohol (OR= 0.14) and tobacco (OR= 1.00)] or in multivariate analysis [alcohol (OR= 0.99) and tobacco (OR= 0.99)]. Conclusion: Our study found that increased consumption of red meat is associated with the presence of CR polyps. However, tobacco and alcohol did not show an association with CR polyps in our study. Larger studies are necessary to validate or challenge our findings.

Hepatitis B virus infection and risk of colorectal cancer: a large, population-based cohort study from Israel.

Recent population-based studies have suggested a possible link between hepatitis B (HBV) infection and extra-hepatic malignancies. We aimed to evaluate the association between HBV and colorectal cancer (CRC) using a large, population-based cohort study utilizing data from a large health maintenance organization (HMO). The study included patients with non-cirrhotic HBV based on relevant ICD-9-CM codes and supportive serology identified from the HMO's database. Age-, sex-, ethnicity-, and BMI-matched non-HBV patients in a 1:10 ratio were included in the control group. We assessed the overall diagnosis rate of CRC and hepatocellular carcinoma (HCC) during the study period and calculated the diagnosis rate of CRC in each age category (≤50, 51-70, and ≥70) in both groups. A total of 3430 HBV patients and 34,300 controls were included in the study. The mean age, sex, BMI, and ethnic composition were similar, and the rates of family history of CRC did not differ between both groups. The overall follow-up period was 134±16 months. The diagnosis rate of HCC (1.6% vs. 0.1%; P<0.0001) was significantly higher in the HBV patients. However, the proportion of CRC was comparable for both groups (0.6% vs. 0.8%, P=0.404), which was evident in all age subgroups. Our findings suggest that HBV infection is associated with an increased risk of HCC diagnosis but is not linked to an elevated risk of CRC. These findings may inform future clinical practice and research regarding the relationship between HBV and extrahepatic malignancies.

Association between oxidative stress exposure and colorectal cancer risk in 98,395 participants: results from a prospective study.

The intricate role of oxidative stress (OS) in colorectal cancer (CRC) initiation is underscored by an imbalance between pro-oxidants and antioxidants. Utilizing the Oxidative Balance Score (OBS) as a metric, this study aims to investigate the association between OS exposure and CRC risk, while also examining potential sex-specific differences in a large U.S. cohort. The study included 98,395 adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. To construct the OBS, 14 dietary and lifestyle factors intricately associated with oxidative stress were quantified. A higher OBS value indicated a more favorable oxidative balance pattern or diminished OS exposure. Due to sex-specific differences in OBS, associations were evaluated separately for men and women based on Cox regression analysis. Subgroup analyses were conducted to elucidate potential modifiers. During 867,963.4 person-years of follow-up, 1,054 CRCs occurred. The mean (SD) age and OBS were 65.52 (5.73) years and 14.09 (3.95) points, respectively. In the fully adjusted Cox model, we observed an inverse association between OBS and CRC incidence in women (HRQ5vsQ1: 0.72; 95% CI: 0.52, 0.99; P for trend = 0.018) but not men. Subgroup analyses revealed the inverse association was more pronounced among women without versus with a family history of CRC (HRQ5 vsQ1: 0.66, 95% CI: 0.47-0.93; P for trend = 0.001; P for interaction = 0.001). The results remained robust after several sensitivity analyses. Higher OBS was associated with lower CRC risk in women but not men; this inverse association was stronger among women without a family history of CRC. These findings suggest exposure to OS may confer sex-specific CRC risk effects, especially for women without a family history of CRC.

Dietary and lifestyle indices for hyperinsulinemia and colorectal cancer risk: a case-control study

BackgroundThe incidence of colorectal cancer (CRC) has increased in Iran, and determining the dietary patterns that can contribute to reducing or increasing the risk of CRC will help better control this disease. Therefore, in the current study, we assessed the association between the empirical lifestyle index for hyperinsulinemia (ELIH) and the empirical dietary index for hyperinsulinemia (EDIH) with the CRC odds.MethodsThe present case (n = 71)-control (n = 142) study was carried out in several CRC surgical units of hospitals in Tehran, Iran. A semi-quantitative food frequency questionnaire containing 168 items was used to assess participants’ dietary intakes. The EDIH and ELIH scores were calculated by food groups and some variables such as body mass index and physical activity. Logistic regression models were applied to evaluate the association between the EDIH and ELIH scores with CRC odds.ResultsAccording to baseline features of the study participants, there were significant differences between the controls and cases in ELIH score, fiber intake, taking aspirin, and family history of CRC in first- and second-degree relatives. Also, we found that the odds of CRC increased significantly in the last tertile compared to the first tertile in EDIH and ELIH in the adjusted model (odds ratio (OR) = 3.12; 95% confidence interval (CI): 1.30–7.48 and OR = 4.72; 95% CI: 1.15–19.39, respectively).ConclusionsIn conclusion, the result of this study indicated that CRC odds was significantly greater in subjects with higher EDIH and ELIH scores. Also, according to the results of this study, lifestyle and diet with insulinemic potential can influence the CRC risk.

Abstract B145: Validation of a colorectal cancer risk prediction model in US Black women

Abstract Background: The National Cancer Institute’s Colorectal Cancer Risk Assessment Tool (NCI-CCRAT) estimates an individual's five-year risk of developing colorectal cancer. It was developed by estimating relative risks from a population of US White women and men and incorporating race, gender, and age-specific incidence data from population-based cancer registries. However, the model performance has not been assessed for Black Americans, who have the highest colorectal cancer incidence and mortality rates of any US racial/ethnic group. Methods: The NCI-CCRAT estimates the absolute risk of colorectal cancer based on an individual’s age, sex, family history of colorectal cancer, sigmoidoscopy/colonoscopy, polyps, smoking, physical activity, regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use, vegetable intake, body mass index, and hormone replacement therapy use. Validation of the NCI-CCRAT was performed using prospective data from 57,558 participants ages 40 to 84 years in the Black Women's Health Study (BWHS). We predicted 5-year absolute risk using data from 2001 through 2015 in three 5-year prediction periods: 2001-2005, 2006-2010, and 2011-2015. To assess model performance, we computed calibration by comparing the expected number of colorectal cancer cases predicted by the model to the observed number of cases (E/O) in the BWHS overall and in subgroups of the population. We assessed discriminatory accuracy by calculating the area under the curve (AUC). Results: During follow-up from 2001 through 2015 (634,512 person-years), 433 BWHS participants developed invasive colorectal cancer. Based on the NCI-CCRAT, 543 cases were expected. The NCI-CCRAT was well-calibrated in the first 5-year prediction period (2001-2005 E/O=1.03, 95% CI: 0.88–1.21), but the model overestimated risk in the subsequent 5-year prediction periods, with E/O=1.30 for 2006-2010 and E/O=1.44 for 2011-2015. The overall E/O ratio was 1.25 (95% confidence interval: 1.14–1.38), indicating that NCI-CCRAT overestimated the number of cases in this population of Black women. Of note, associations with colorectal cancer were weaker in the BWHS than in the development cohort for vigorous physical activity, aspirin/NSAID use, vegetable intake, and body mass index. We estimated discriminatory accuracy only for the first 5-year prediction period (2001-2005, N cases=151) for which the model was well calibrated, and obtained an age-adjusted AUC of 0.61 (95% CI: 0.57–0.66). Conclusions: The NCI-CCRAT overestimated the overall number of colorectal cancer cases by 25% in this prospective cohort of Black women, possibly due to population-specific differences in the relative risks of key factors driving colorectal cancer incidence. Discriminatory accuracy was similar to measures from the original validation cohort of White women and men. Impact: This study suggests that further research is needed to determine the most important predictors of colorectal cancer etiology in Black women and to develop and test a colorectal cancer risk prediction model for Black Americans. Citation Format: Jessica L. Petrick, Nelsy Castro-Webb, Gary R. Zirpoli, Kerrie P. Nelson, Julie R. Palmer, Ruth M. Pfeiffer. Validation of a colorectal cancer risk prediction model in US Black women [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 B145.

Endoscopic and histopathological characteristics of polyp and colorectal cancer in people with a family history of colorectal cancer

Background: According to Globocan statistics in 2018, there were estimated 1.8 million cases of colorectal cancer and 881,000 deaths. The rate of colorectal cancer is tending to increase in people under 50 years old. According to the 2017 American Society for Gastrointestinal Endoscopy guidelines, Colonoscopy every 5 years beginning 10 years before the age at diagnosis of the youngest affect interval or age 40, whichever is earlier; for those with a single first-degree relative with colorectal cancer in whom no significant neoplasia appears by age 60 years, physicians can offer expanding the interval between colonoscopies. Objectives: (1) T o describe clinical features, endoscopic images, histopathology of polyps and colorectal cancer of first-degree relatives with colorectal cancer. (2) To determine the relationship between risk polyps and colorectal cancer with some factors. Materials and method: Cross-sectional study analyzing all first-degree relatives aged ≥ 40 years or approximately 10 years younger than the age of the patient diagnosed with colorectal cancer undergoing colonoscopy at the Functional Examination Department, Gia Dinh People’s Hospital during the period from June 2019 to December 2019. Results: In 85 cases: The main features of endoscopy were: rectal polyps 47.3%, sizes &lt; 5 mm 63.9%, multiple polyps 52.7%, sessile 91.7% and smooth surface 88.9%. Regarding histopathological characteristics: the proportion of adenomatous polyps and serrated polyps is nearly equal. Mild dysplasia accounts for the highest rate of 84.2%, high dysplasia accounting for 15.8%. There was 1 case of colorectal cancer, in the sigmoid colon, an ulcerative cancer. Factor related to colorectal polyps and colorectal cancer is age, other factors (gender, smoking, alcohol and abesity) didn’t relate. Conclusion: Our result shows that the majority of polyps are located in the rectum, adenomatous polyps and serrated polyps account for nearly equal proportions, there is a relationship between colon polyps and age, there is no relationship between colon polyps. with gender, smoking, alcohol and obesity. Key words: Colonoscopy, colorectal cancer, first-degree relative, polyp.

Abstract A017: Evaluation of ¡Salud! por la Vida, an educational intervention to increase colorectal cancer screening in federally qualified health centers in Puerto Rico

Abstract Introduction: Colorectal cancer (CRC) is the leading cause of cancer-related deaths in Puerto Rico (PR) and third among Hispanics in the United States (US). Screening rates in PR are relatively low compared to the mainland US. Objective: To evaluate the effectiveness of “¡Salud! por la Vida”, an evidence-based educational intervention designed to increase CRCS. Methods: The educational intervention “¡Salud! por la Vida” (SPLV) was implemented in 10 Federally Qualified Health Clinics (FQHC) in PR to increase CRC screening (CRCS) rates in non-adherent patients aged 50 to 75. SPLV was conducted as a group randomized controlled trial from July 2017 to July 2020. The intervention included a baseline survey collecting 198 variables and a follow-up survey 4 to 6 months later, which included 148 variables to measure the effectiveness of the educational program in increasing CRCS. The initial surveys had some changes to improve the data entry process. Consequently, the database required an updated data analysis consisting of data exploration, data cleaning, and statistical analysis. Prior to calculating results, data cleaning included identifying missing variables, inconsistencies in the data, and missing data. The final dataset for this project concerns participants who completed the follow-up survey, divided into intervention and control groups. The analysis calculated basic demographics in proportions, such as age, education, sex, marital status, annual income, health insurance coverage, and first-degree family history of CRC. Furthermore, the two groups were compared regarding CRCS rates, specifically those of colonoscopy, fecal occult blood test (FOBT), and having completed any CRCS. Results: A total of 445 individuals participated in the study. At baseline, 332 were from the control group and the rest from the intervention group. The follow-up survey was completed by 295 participants in the control group and 78 participants in the intervention group, for a total of 373 at follow-up. The mean age of participants who completed the study was 58.9, with 68.9% of participants being women. 70.5% had an education of high school or less, 45.3% were married or living together, 93% earned less than $20,000 a year, 87.9% had government health insurance, and 88.2% had no first-degree family history of CRC. CRCS tests were completed by 60.2% of those in the intervention group and 38.3% of control group participants (p-value 0.001). FOBTs were done by 55.1% and 36.9% of the intervention and control group participants, respectively (p-value 0.005). In the intervention group, 10% of the participants completed a colonoscopy, while in the control group, 3% had completed a colonoscopy (p-value 0.02). Conclusion: CRCS rates were higher in the intervention groups, for both colonoscopy (p-value 0.008) and FOBT (p-value 0.003), as well as any CRCS test (p-value 0.0004). The SPLV intervention significantly increased CRC screening rates and provided evidence to disseminate this educational effort to FQHCs in PR. Citation Format: Jomarie Jiménez-González, Fernando E. Betancourt-Vélez, Ileska M. Valencia-Torres, Yara Sánchez-Cabrera, Luis R. Pericchi-Guerra, María E. Fernández, Vivian Colón-López. Evaluation of ¡Salud! por la Vida, an educational intervention to increase colorectal cancer screening in federally qualified health centers in Puerto Rico [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 A017.

High polygenic risk score is a risk factor associated with colorectal cancer based on data from the UK Biobank.

Colorectal cancer (CRC) is a common cancer among both men and women and is one of the leading causes of cancer death worldwide. It is important to identify risk factors that may be used to help reduce morbidity and mortality of the disease. We used a case-control study design to explore the association between CRC, polygenic risk scores (PRS), and other factors. We extracted data about 2,585 CRC cases and 9,362 controls from the UK Biobank, calculated the PRS for these cases and controls based on 140 single nucleotide polymorphisms, and performed logistic regression analyses for the 11,947 cases and controls, for an older group (ages 50+), and for a younger group (younger than 50). Five significant risk factors were identified when all 11,947 cases and controls were considered. These factors were, in descending order of the values of the adjusted odds ratios (aOR), high PRS (aOR: 2.70, CI: 2.27-3.19), male sex (aOR: 1.52, CI: 1.39-1.66), unemployment (aOR: 1.47, CI: 1.17-1.85), family history of CRC (aOR: 1.44, CI: 1.28-1.62), and age (aOR: 1.01, CI: 1.01-1.02). These five risk factors also remained significant in the older group. For the younger group, only high PRS (aOR: 2.87, CI: 1.65-5.00) and family history of CRC (aOR: 1.73, CI: 1.12-2.67) were significant risk factors. These findings indicate that genetic risk for the disease is a significant risk factor for CRC even after adjusting for family history. Additional studies are needed to examine this association using larger samples and different population groups.

Association between metabolic syndrome and the risk of colorectal cancer: a prospective study in China.

To evaluate the correlation between metabolic syndrome (MetS) and its components on the incidence of colorectal cancer (CRC) based on data from Jinchang Cohort. This is a large prospective cohort study. Between 2011 and 2020, a total of 43 516 individuals from Jinchang Cohort were included for this study. Hazard ratios (HRs) with 95% confidence intervals (CIs) for CRC according to MetS were calculated with the Cox proportional hazard models. The restricted cubic spine models with four knots were conducted to fit the dose-response relationships. MetS was associated with increased risk of CRC (n = 141; HR: 1.64, 95% CI: 1.15-2.33) after adjusting for confounding factors (age, sex, education level, family history of CRC, smoking index and alcohol index). Participants with hyperglycemia had a significantly higher risk of developing incident CRC (HR: 1.70; 95% CI: 1.19-2.43). The positive association between MetS and CRC was observed in males (HR: 1.76; 95% CI: 1.17-2.63), but not in females (HR: 1.24; 95% CI: 0.59-2.64). Furthermore, linear dose-response relationship was found between fasting plasma glucose (FPG) and CRC risk in males ( Poverall < 0.05, Pnon-linear = 0.35). When stratified by smoke and drink, MetS was found to increase the incidence of CRC only in the smoke (HR: 2.07, 95% CI: 1.35-3.18) and drink (HR: 2.93, 95% CI: 1.51-5.69) groups. MetS was associated with a higher risk of CRC incidence. Hyperglycemia lended strong support to the role of MetS in new-onset CRC, especially in males. Other components of MetS were not found to be associated with increased risk of CRC.

Revisiting the Prognostic Impact of Family History in Colorectal Cancer by Retrospective Propensity Score Matching.

Family history of colorectal cancer (CRC) is a known risk factor for CRC. However, its prognostic value in patients with CRC remains controversial. This study aimed to clarify the prognostic impact of a family history of CRC. We retrospectively reviewed the database from 1978 to 2018 and enrolled 3,655 consecutive patients with CRC. We investigated the clinicopathological factors of patients with CRC with and without a family history. After propensity score matching, we performed a survival analysis of patients with CRC with and without a family history. Patients with CRC with a family history of CRC had a young onset (63.2 and 65.9; p<0.001), were more likely to be female (54.3% and 49.7%; p=0.042), had less symptomatic disease (76.9% and 80.8%; p=0.008), were more likely to have right-sided colon cancer (27.5% and 26.1%), and had less distant metastases (11.3% and 14.9%; p=0.023) and multiple CRCs (10.2% and 7.8%) compared with those without a family history of CRC. Prior to propensity score matching, CRC-specific survival analysis showed that a family history of CRC was a good prognostic factor (p=0.022). After propensity score matching, survival curves overlapped between the two groups. Patients with CRC with a family history of CRC had specific clinicopathological features including younger onset, female sex, proximal colon location, fewer symptoms, smaller number of distant metastases, likelihood of multiple diseases, and earlier cancer stage. Family history of CRC in patients with CRC was not a prognostic factor.

Referral, Uptake, and Outcome of Genetic Counseling and Testing in Patients With Early-Onset Colorectal Cancer.

The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing. Pathogenic germline variants (PGVs) are detected in 16% to 20% of patients who have EOCRC, highlighting a need for genetic counseling (GC) and multigene panel testing in these patients. We aimed to determine the rate of referral to GC and uptake and outcomes of germline testing in patients with EOCRC. We conducted a retrospective cohort study of patients aged <50 years diagnosed with colorectal cancer (CRC) from 2010 to 2019 at Cleveland Clinic. Demographic data were extracted, including age, sex, self-reported race, and family history of CRC. The proportions of patients with GC referral and completion of GC and genetic testing were investigated, and genetic testing results were analyzed. Multivariable logistic regression analysis was conducted to identify factors independently associated with GC referral and uptake. A total of 791 patients with EOCRC (57% male and 43% female) were included; 62% were referred for GC, and of those who were referred, 79% completed a GC appointment and 77% underwent genetic testing. Of those who underwent testing, 21% had a PGV detected; 82% were in known CRC-associated genes, with those associated with Lynch syndrome and familial adenomatous polyposis the most common, and 11% were in other actionable genes. Referral to GC was positively associated with family history of CRC (odds ratio [OR], 2.11; 95% CI, 1.51-2.96) and more recent year of diagnosis (2010-2013 vs 2017-2019; OR, 5.36; 95% CI, 3.59-8.01) but negatively associated with older age at diagnosis (OR, 0.89; 95% CI, 0.86-0.92). Referral to GC for patients with EOCRC is increasing over time; however, even in recent years, almost 25% of patients were not referred for GC. We found that 1 in 5 patients with EOCRC carry actionable PGVs, highlighting the need for health systems to implement care pathways to optimize GC referral and testing in all patients with EOCRC.

Impact of Various Risk Factors on the Positive Fecal Immunochemical Test for Colorectal Cancer in the Iranian Population.

Background: Colorectal cancer (CRC) is the most prevalent cancer with high mortality worldwide. We aimed to evaluate the incidence of CRC based on the positive fecal immunochemical test (FIT) result in the Iranian population. Methods: The present study was conducted on the health assessment data recorded in the SINA (Integrated Health Information System) in 2018 and 2019 from individuals who had participated in the national program, including asymptomatic people aged 50-69 years or had risk factors of CRC such as family or past personal history of CRC as well as symptomatic individuals, for the early detection and prevention of CRC in Mashhad, Iran. Results: The study participants included 140,463 eligible individuals, of whom 8258 (5.88%) and 145 (2.21%) were positive for FIT and diagnosed with colon cancer, respectively. Unfortunately, only 654 people had undergone colonoscopy. Our results indicated that age, fast food intake (≥two units per day), family history of CRC in first or second-degree relatives, some gastrointestinal diseases such as inflammatory bowel disease (IBD) and CRC, as well as bleeding per anus, constipation, abdominal cramp, and losing body weight were associated with increased risk of positive FIT. However, some other factors, including having a hard job, physical activity, and Iranian nationality (compared to non-Iranians), were associated with a low risk of positive FIT screening tests for CRC. Conclusion: A high number of high-risk persons in Mashhad were positive for the FIT test in 2018-2019, and many of them were diagnosed with CRC, according to the colonoscopy results. Therefore, screening is highly recommended as the first step in the early detection of CRC.

Colorectal neoplasia surveillance in inflammatory bowel disease

Performing colorectal neoplasia surveillance in persons with inflammatory bowel disease (IBD) that is both clinically effective and cost effective is among the greatest challenges facing endoscopists who care for this population. While heightened colorectal cancer (CRC) risk has long been recognized among persons with IBD, this risk has been declining over time, with recent reports suggesting no more than a 1.5–2-fold higher risk compared to age and sex matched members of the general population. Nonetheless, given that CRC still occurs at a higher rate in this population, current surveillance strategies are inadequate for some persons. Conversely, 80–90% of persons with IBD had no neoplastic lesions identified during colonoscopy surveillance, suggesting that many persons with IBD are unnecessarily exposed to the risks of colonoscopy, with society bearing these excess costs.&#x0D; The purpose of colorectal neoplasia surveillance is to reduce the burden of CRC and CRC-related death in the IBD population. Societal guidelines recommend initiating colorectal neoplasia screening with colonoscopy in all persons with colorectal IBD involving at least the rectosigmoid (or at least 1/3 of the colorectum if accompanied by discontinuous inflammation) at 8–10 years following disease diagnosis and continuing lifelong surveillance every 1–5 years. Major factors influencing surveillance frequency include historical disease severity, extent of colorectal inflammation, chronic post-inflammatory changes, family history of CRC, history of colorectal neoplasm, primary sclerosing cholangitis, prior colonoscopy findings, and adequacy of prior surveillance. All guidelines further recommend targeted sampling or resection of suspicious visible abnormalities, and some societies continue to recommend extensive non-targeted biopsies to detect “invisible” neoplasia, particularly if other adjunctive optical modalities, such as dye-spray chromoendoscopy (DCE) or virtual chromoendoscopy (VCE), are not performed, or if the mucosa is poorly visualized, such as in areas of significant inflammation, post-inflammatory polyposis, or poor bowel preparation. Most societies now advocate for DCE or VCE as primary screening tools for IBD neoplasia surveillance or, at a minimum, as alternative modalities to traditional white light colonoscopy with non-targeted biopsies where resources and expertise exists.&#x0D; However, there are no prospective studies demonstrating a reduction in the incidence of CRC or of death from CRC with current surveillance strategies in persons with IBD. Furthermore, observations from large retrospective studies are also conflicting. A Cochrane analysis of 3 studies in persons with UC did not find a significant mortality benefit for current surveillance strategies. Considering that IBD afflicts many persons at a young age, is rising in prevalence in Canada and globally, and requires intensive lifelong surveillance , the amount of endoscopy resources directed toward IBD surveillance is potentially enormous. Increasing demands on colonoscopy resources from expansion of population-based CRC screening programs and an aging population are likely to challenge the ability to continue to provide intensive surveillance to all persons with IBD. Optimizing delivery of limited colonoscopy resources will thus be essential to maintain effective CRC prevention programs in this population.&#x0D; Current standards for neoplasia surveillance in IBD have been recently updated. Shah and Itzkowitz authored a comprehensive review that includes epidemiology, pathogenesis, and management of colorectal neoplasia, along with a chart that compares surveillance recommendations put forward by multiple societies. The present review will highlight new evidence influencing neoplasia surveillance and provide practical approaches for surveillance and management of neoplastic lesions in the IBD population.

Personalized Initial Screening Age for Colorectal Cancer in Individuals at Average Risk

Colorectal cancer (CRC) risk varies widely in the population at average risk without a family history, but there are no established routines for translating this variation into personalized starting ages of screening. To illustrate derivation of risk-adapted starting ages of CRC screening based on the concept of risk advancement period (RAP) using sex and a polygenic risk score (PRS) as an example. This cohort study included participants in the UK Biobank study recruited in England, Wales, and Scotland between March 13, 2006, and October 1, 2010. Participants were aged 40 to 69 years, with no previous bowel cancer screening and no family history of CRC. Follow-up of cancer data was completed February 29, 2020, for England and Wales and January 31, 2021, for Scotland. The censoring date for death data was September 30, 2021, for England and Wales and October 31, 2021, for Scotland. Data on age, sex, and family history were collected at the baseline interview. A PRS was calculated based on 139 CRC-related risk loci. Hazard ratios (HRs) of sex and PRS with CRC risk and mortality were estimated using Cox proportional hazards regression models and were translated to RAPs to quantify how many years of age earlier or later men and individuals in higher or lower PRS deciles would reach risks comparable with those of the reference group (ie, women or those in the 5th and 6th PRS deciles). Among 242 779 participants (median age, 55 [IQR, 48-61] years; 55.7% women), 2714 incident CRC cases were identified during a median follow-up of 11.2 (IQR, 10.5-11.8) years and 758 deaths during a median follow-up of 12.8 (IQR, 12.0-13.4) years. The HRs of CRC risk were 1.57 (95% CI, 1.46-1.70) for men vs women and ranged from 0.51 (95% CI, 0.41-0.62) to 2.29 (95% CI, 2.01-2.62) across PRS deciles compared with the reference. The RAPs were 5.6 (95% CI, 4.6-6.6) years for men vs women and ranged from -8.4 (95% CI, -11.0 to -5.9) to 10.3 (95% CI, 8.5-12.1) years across PRS deciles compared with the reference deciles. Risk-adapted starting ages of screening would vary by 24 years between men in the highest PRS decile and women in the lowest PRS decile. Similar results were obtained regarding CRC mortality. In this large cohort study including women and men at average risk of CRC, risk-adapted starting ages of screening strongly varied by sex and a PRS. The RAP concept could easily accommodate additional factors for defining personalized starting ages of screening.