CRC Mortality Research Articles

Fecal Hemoglobin Concentrations and Personalized Screening for Colorectal Cancer

Background: Although cancer screening programs have been established in some Asian countries, resources are still insufficient to maintain high participation rates. The aim of this study was to assess whether any observed relationship persisted after adjusting for the pathologic stage of CRC to assess whether the increasing fecal hemoglobin (f-Hb) concentration on the risk of CRC death is partially explained by its intermediate influence on the pathologic stage of CRC and to propose the risk stratification by using f-Hb concentration for developing individual-tailored CRC screening. Methods: Over 1 million Taiwanese residents (n = 1,160,895) aged between 50 and 69 years participated in a biennial nationwide fecal immunochemical test (FIT) screening program between 2004 and 2009. The cohort was followed up over time to ascertain colorectal neoplasia and the causes of death until 2012. Cox regression model was operated to validate the definition of the surrogate end point such as tumor stage for the effect of f-Hb on CRC mortality and test the relationships between f-Hb in groups with increasing f-Hb and CRC mortality. The individual risk profiles based on f-Hb are proposed starting from average risk group to low risk and high risk group with biennial interscreening interval for risk prediction in advance colorectal cancer. Results: An incremental increase in both of baseline and updated f-Hb on the risk of advanced CRC cancer and CRC mortality were noted. A significant relationship was found between f-Hb and the risk for CRC mortality, increasing from a slightly increased risk for the category of f-Hb of 6 to 9 μg Hb/g (adjusted hazard ratio [HR] = 1.88; 95% CI, 1.41-2.50) to 33.04 (95% CI, 24.87-43.91) for the group with f-Hb ≥ 450 μg Hb/g as compared with the group with f-Hb of 1 to 5 ng Hb/mL (trend test, P < 0.001) at baseline after adjusting for age, gender. Taking 10-14 μg Hb/g (similar CRC mortality as general population) as standard, subjects with higher f-Hb at first screen should have a shorter interscreening interval with FIT. The screening interval could be altered to 1.5 year and 1 year for subjects with f-Hb of 15-19 μg Hb/g and f-Hb of 20-49 μg Hb/g, respectively. On the other hand, the interval between repeated FIT screens could be extended to avoid false positive cases for those with a lower f-Hb. The screening interval could be lengthened as 3 year for subjects with f-Hb of 6-9 μg Hb/g. Conclusion: We confirmed the direct relationship between f-Hb and colorectal cancer mortality, which is explained by the role of f-Hb as a surrogate for advanced CRC. Different interscreenings by different f-Hb concentrations are recommended. Individualized interscreening intervals by different f-Hb level or together with other factors could be further considered for personalized CRC screening.

Colorectal Cancer Incidence and Mortality Rates Among New York City Adults Ages 20-54 years during 1976-2015.

Colorectal cancer (CRC) incidence rates are rising in younger Americans and mortality rates are increasing among younger white Americans. We used New York State Cancer Registry data to examine New York City CRC incidence and mortality trends among adults ages 20–54 years by race from 1976 to 2015. Annual percent change (APC) was considered statistically significant at P less than .05 using a two-sided test. CRC incidence increased among those ages 20–49 years, yet blacks had the largest APC of 2.2% (1993–2015; 95% confidence interval [CI] = 1.4% to 3.1%) compared with 0.5% in whites (1976–2015; 95% CI = 0.2% to 0.7%). Among those aged 50–54 years, incidence increased among blacks by 0.8% annually (1976–2015; 95% CI = 0.4% to 1.1%), but not among whites. CRC mortality decreased among both age and race groups. These findings emphasize the value of local registry data to understand trends locally, the importance of timely screening, and the need for clinicians to consider CRC among all patients with compatible signs and symptoms.

Results of an Electronic Patient Survey to Determine Up-to-Date Colorectal Cancer Screening Status and Identify High-Risk Individuals

Introduction: The incidence and mortality of colorectal cancer CRC has declined dramatically, due to improved screening which prevent and detect CRC in its earliest stages. However, screening rates continue to be suboptimal, especially in high-risk individuals. This disparity is partially attributable to the difficulty in identifying high-risk individuals who require more intensive screening. Methods: We devised a one-page IRB-approved patient survey that determined if a patient was up-to-date on CRC screening based on 2016 USPSTF guidelines. The survey was administered to Penn State Health employees ≥ 40 years via the RedCap online platform through the Department of Human Resources. The survey anonymously collected data on demographic information and CRC screening tests. The survey also included a checklist of five questions including a previously validated hereditary CRC risk assessment tool to help identify high-risk patients. Associations between demographic/risk factors and up-to-date screening status were examined using Fisher’s exact test for categorical variables and Wilcoxon Rank-Sum test for quantitative variables. Results: Questionnaires were administered to 6,188 employees, with a response rate of 45%. 2,638 met inclusion criteria and were included in statistical analysis. Eighty percent of respondents were females. For respondents ≥ 50 years, 81% reported up-to-date CRC screening; 76% of 50-59 year olds, 92% of 60-69 year old, and 100% of ≥ 70 year olds. There was no difference in screening rates by gender or race. Colonoscopy was the most common screening method (78%). Thirty-three percent of all participants self-identified as high-risk; 77.7% reporting up-to-date CRC screening. Twenty-five percent of participants aged 40-49 self-identified as high-risk, but only 46% reported up-to-date screening. Conclusion: Our short electronic questionnaire championed by our Human Resources Department was a novel and efficient way to evaluate a large number of patients to determine CRC screening rates and identify high-risk individuals. It utilized familiar technology, easily administered and completed, as evidenced by a high response rate. Our survey increased CRC screening awareness, identified and measured screening rates in younger, “at-risk,” individuals. Our institution met the CRC screening target of “80% by 2018.” This tool could be used by any large employer to measure their CRC screening rates.

Abstract C75: Diagnosing CRC in 3 vulnerable health centers in Santiago, Chile. Not an easy task

Abstract Colorectal cancer (CRC) is a common cancer worldwide. In Chile it is the third leading cause of cancer mortality. Its incidence rate is about 14 per 100,000 inhabitants. It is known that there is an inverse relationship between GDP per capita and CRC mortality. In Chile it is estimated that for every 3 people with CRC two deaths occur, while in the United States this number is one death per 6 people diagnosed. The Chilean Health care system is a dual one; the public sector serves >70% of the population with 50% of the resources. The private sector serves <30% of the population and uses up the other 50%. Delays in diagnosis that may occur are multifactorial. An important factor is the low availability of colonoscopies. In Chile this resource is limited mainly in the public system, where most of low-income population is served. In Santiago, the South East Health Service (SSMSO) is a part of the public system and serves a population of about 1,500,000 inhabitants. Data from one of the three hospitals in the SSMSO show that 2/3 of referred patients arrive with advanced-stage CRC at the time of diagnosis. Our hypothesis is that there is a delay in the diagnostic process in the SSMSO inhabitants. To improve it, points of delay must be identified. This pilot study aims to describe CRC diagnosis in three primary care center (PCC) of the SSMSO from initial symptoms to endoscopic confirmation, estimating possible times of delay to the diagnosis. With this information we hope to propose interventions that will allow the articulation of primary, secondary and tertiary care for early CRC diagnosis. Methods: Retrospective cohort study in 3 PCC. Collection of data was made through electronic medical records (EMR). We selected and reviewed all EMR with diagnosis of CRC from 2010 to march 2017. Demographic data, initial symptoms, secondary referrals, and place of diagnosis were extracted. With these data incidence, characterization of patients with CRC and estimation of waiting times were determined. Results: We reviewed 60,783 EMR from eligible men and women. We found 22 people with confirmed CRC with an incidence of 4,4 per 100,000 inhabitants. The average age at diagnosis was 64.3 years; 45% (10) were men and 55% (12) women. 50% (11) of them had their diagnosis made in the private system. There were records of early symptoms in 63% (14) of patients. 43% (6) had weight loss, 36% (5) hematochezia, 21% (3) abdominal pain, 14% (2) anemia, 14% (2) diarrhea, 14% (2) change in bowel habit, 14% (2) palpable mass, and 13% (2) had been diagnosed due to an acute complication. Regarding waiting times, 4 people had a recorded time from symptoms to first consultation, which was 4.7 months on average. In one patient the time from symptoms to diagnosis was 9 months. 8 people had the time from referral to specialist evaluation on their EMR, which was 23.5 days on average. 7 of these patients were referred with a diagnosis already made. Conclusion: There is a severe lack of information regarding CRC diagnosis. Data obtained through this pilot study were scarce and insufficient to estimate the waiting times between the symptoms and the diagnosis of CRC. One of the reasons for this lack of diagnosis might be that information systems in primary, secondary, and tertiary care are not connected, thus making it impossible to access patient information that might have been diagnosed in the hospitals and stayed there for the whole durations of their treatment. Through these results we might also infer that a large percentage of our patients were diagnosed outside the public network, probably because of the long waiting times for a colonoscopy in the public sector. This could explain the low incidence of CRC. It is necessary to carry out more studies that include secondary-level data as well as qualitative data to determine the diagnostic process of CRC more accurately. Citation Format: Viviana Rodríguez, María Jesús Valdivieso, Felipe Quezada, Maria Elisa Herrera, Javiera Martínez-Gutiérrez. Diagnosing CRC in 3 vulnerable health centers in Santiago, Chile. Not an easy task [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C75.

Abstract 267: Nonsteroidal anti-inflammatory drugs induce ER stress- and BID-dependent immunogenic cell death to suppress colorectal tumorigenesis

Abstract Prevention or early detection represents a key approach for reducing the mortality and morbidity of CRC. Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with decreased risk of CRC in numerous epidemiological studies, clinical trials, and animal model studies. However, the mechanism by which NSAIDs suppress colorectal tumorigenesis has remained unclear. We previously demonstrated that the chemopreventive effect of NSAIDs is mediated by a synthetic lethal interaction between death receptor signaling and loss of the gatekeeper APC tumor suppressor, which is dependent on the BH3-only Bcl-2 family member BID. In this study, we found a critical role of endoplasmic reticulum (ER) stress upstream of death receptor signaling and BID activation. Elevated levels of ER stress and cell death markers were detected in advanced adenomas from patients taking NSAIDs including aspirin. Inhibiting ER stress using a pharmacological approach abolished the apoptotic effect of NSAIDs in CRC cells and normal colonic epithelial cells with APC loss and also suppressed the chemopreventive activity of the NSAID sulindac in APCMin/+ mice. Importantly, our results unveiled a critical role of ER stress and BID-dependent cell death in triggering immune-mediated elimination of nascent cells that lose APC. Markers of immunogenic cell death (ICD), including plasma membrane translocation of calreticulin and phagocytosis by dendritic cells, were suppressed in cells with BID knockout or ER stress inhibition. BID knockout or ER stress inhibition also reduced tumor infiltrating lymphocytes (TILs) in sulindac-treated APCMin/+ mice. Collectively, our results suggest that NSAIDs suppress colorectal tumorigenesis by enhancing immunosurveillance through ER stress and BID-dependent ICD. These results provide novel insight into the chemopreventive mechanism of NSAIDs, which may help design more effective chemopreventive strategies and agents. Citation Format: Rochelle Elayne Fletcher, Brian Leibowitz, Yijun Wang, Fernando Concha-Benavente, Robert Ferris, Robert Schoen, Jian Yu, Lin Zhang. Nonsteroidal anti-inflammatory drugs induce ER stress- and BID-dependent immunogenic cell death to suppress colorectal tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 267.

Abstract IA19: Cancer chemotherapy and the tools needed to advance treatment in a medical diverse population

Abstract Colorectal cancer (CRC) is the third most commonly diagnosed cancer and is the third leading cause of cancer-related deaths in the Western world. The mortality from colorectal cancer in Caucasian American (CAs) has been declining, but the death rate continues to be higher in African Americans (AAs), maintaining the racial disparity. In addition, AAs more often present with CRC at advanced stages contributing to the lower five-year survival rate. Hispanic-Americans (HAs) have significantly lower CRC incidence and mortality rates when compared with non-Hispanic AA (NH-AA) and non-Hispanic CA (NH-CA) populations. However, rates among HAs are significantly higher than those among residents of Puerto Rico and other Spanish-speaking countries in South and Central America. Furthermore, preliminary data and documented results show that for HA the age at presentation is lower and the stage of the disease is higher than that of AA and CAs. We hypothesize that various factors (i.e., familial, socioeconomic, environmental, and dietary) may contribute to the underlying problem of colon cancer racial/ethnic health disparity. Also, it has been noted that the response to chemopreventive agents differ as to the biologic/genetic heterogeneity of the tumors of NH-AAs, Has, and NH-CAs. Since chemopreventive agents exert their effect through a molecular target, this disparity would suggest differences at the genetic level. Therefore, the formulation and evaluation of chemopreventive/chemotherapeutic agents that address the issue of differential chemoresponse and chemoresistance is essential to survival. To study, in vitro and in vivo, the development of and chemoresponsiveness of therapeutic agents to colonic diseases in diverse populations, the availability of the appropriate cells (cell lines/organoids) and animal (PDX) models is critical. Our overarching goal is to assess racial and ethnic genetic/epigenetic dysregulations and associate these changes to chemoresponse and colon cancer racial disparity. The availability of these biologic tools will facilitate overcoming differential incidence and outcome seen among racial and ethnic groups for CRC. To achieve this goal, we are generating and characterizing novel cell lines, PDXs, and organoids derived from NH-CAs, Has, and AAs patients with colorectal cancer. Downstream use of these biologic tools will assist our group and the scientific community at large in improving targeted personal cancer treatment. This research effort is inclusive of all and will benefit a diverse population. Citation Format: Jennie L. Williams. Cancer chemotherapy and the tools needed to advance treatment in a medical diverse population [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA19.

New frontiers in fecal immunochemical and other fecal tests in colorectal cancer screening

Since 1993, fecal immunochemical tests for hemoglobin (FIT-Hb) have been used as an initial test in CRC screening programs (1,2,3) and a large amount of data have supported the efficacy of this strategy to reduce CRC mortality (3,4). In addition, new evidence of a reduced CRC incidence in subjects enrolled in long term screening programs comes from about 2,000 reports (4,5).

Colorectal cancer in the world: incidence, mortality and risk factors

A rapid literature search strategy was conducted for all English language literature published before July 2017. The search was conducted using the electronic databases PubMed, Scopus and Web of Science. The search strategy included the keywords ‘colorectal cancer’, ‘epidemiology’, ‘incidence’, ‘mortality’, ‘risk factor’, and ‘world’. In 2012, the highest CRC incidence rates were observed in the Republic of Korea, Slovakia and Hungary while the lowest incidence rates were seen in Singapore, Serbia and Japan. The highest CRC mortality rates in both sexes were seen in Central and Eastern Europe and the lowest mortality rates were found in Middle Division of Africa. The main risk factors for CRC include nutritional factors, past medical history, smoking, socioeconomic status, and family medical history. According to the increasing trend of CRC incidence and mortality in the world, implementation of prevention programs such as screening programs, diet modification, and healthy lifestyle education is necessary.
 Peer Review Details
 
 
 
 
 
 Peer review method: Single-Blind (Peer-reviewers: 02) Peer-review policy 
 Plagiarism software screening?: Yes
 Date of Original Submission: 26 August 2017
 Date accepted: 20 Sept 2017
 Peer reviewers approved by: Dr. Lili Hami 
 Editor who approved publication: Dr. Phuc Van Pham
 
 
 
 
 

BMI Is a Risk Factor for Colorectal Cancer Mortality.

The relationship between dietary and lifestyle risk factors and long-term mortality from colorectal cancer is poorly understood. Several factors, such as obesity, intakes of red meat, and use of aspirin, have been reported to be associated with risk of colorectal cancer mortality, though these findings have not been replicated in all studies to date. In the Minnesota Colon Cancer Control Study, 46,551 participants 50-80years old were randomly assigned to usual care (control) or annual or biennial screening by fecal occult blood testing. Colon cancer mortality was assessed after 30 years of follow-up. Dietary intake and lifestyle risk factors were assessed by questionnaire at baseline. Age [hazard ratio (HR) 1.09; 95% CI 1.07, -1.11], male sex (HR 1.25; 95% CI 1.01, 1.57), and higher body mass index (BMI) (HR 1.03; 95% CI 1.00-1.05) increased the risk of CRC mortality, while undergoing screening for CRC was associated with a reduced risk of colorectal cancer mortality (HR 0.76; 95% CI 0.61-0.94 and 0.67; 95% CI 0.53-0.83 for biennial and annual screening, respectively). Intakes of grains, meats, proteins, coffee, alcohol, aspirin, fiber, fruits, and vegetables were not associated with colorectal cancer mortality. Our study confirms the relationship between BMI and long-term colorectal cancer mortality. Modulation of BMI may reduce risk of CRC mortality.

Abstract 3496: Long non-coding RNAs in colorectal cancer

Abstract Colorectal cancer (CRC) is the third most common type of cancer worldwide and the second most common cause of cancer related deaths in Europe. Since Countries of Central Europe (Czech Republic, Slovakia, Hungary) have one of the highest rates both for incidence and mortality of CRC, CRC became a serious health, social and economic problem. CRC pathogenesis involves multiple genetic events. On behalf of a strong experimental work, there is still lack of predictive, prognostic and treatment-response related biomarkers. Long non-coding RNAs (lncRNA) are non-protein coding transcripts longer than 200 nucleotides. Deregulation of lncRNAs is often seen in a variety of human diseases, including cancer. Taken together, this makes lncRNAs the potential regulators of cancer progression, therapeutic targets or markers of treatment efficacy. The main aim of our present study was to define expression patterns of lncRNAs in colorectal tumor tissue and define their role in cancer cell proliferation, survival and DNA damage response (DDR). In the first part of our study, we analyzed the expression profile of 83 lncRNA known to be associated with cancer progression in cohort of CRC tumor tissues and adjacent mucosa. We found 12 upregulated lncRNAs (p<0.05) and 10 downregulated lncRNAs (p<0.05). Our results have been replicated on larger set of patients (100 CRC patients) and those lncRNAs associated with cell proliferation, survival and DNA damage response are functionally tested on colorectal cell lines (HCT116, HCT116 p53-/-) in vitro. Definition of role of lncRNA as a tumor suppressors or oncogenes in CRC etiology may lead to better understanding of regulation of CRC carcinogenesis. Furthermore, understanding the role of lncRNA in DDR may contribute to better treatment response of CRC patients and to define markers of individual treatment response. Acknowledgement: GACR 15-14789S, AZV 15-27580A, GAUK800216, AZV 15-26535A, SUSCEPTCOST LD14050 Citation Format: Alena Opattova, Fábio Miguel Ferreira, Jozef Horak, Sona Vodenkova, Pavel Vodicka. Long non-coding RNAs in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3496. doi:10.1158/1538-7445.AM2017-3496

Abstract SY14-01: Colon cancer screening and genetics

Abstract Colorectal cancer (CRC) is the third most prevalent and second deadliest cancer in the U.S. with 134,490 cases and 49,190 deaths in 2016. Its pathogenesis stems from genetic susceptibility coupled with environmental interactions in the colon that synergize ideal conditions for neoplastic growth, initially from benign adenomatous polyps that might progress to carcinoma over several years. Adenoma initiation and progression to carcinoma may take one of a few identified genetic pathways that determine the tempo of progression as well as morbidity and mortality of the patient. Each patient’s CRC is genetically unique with variable numbers of passenger mutations and propelled by 2-8 driver mutations. CRCs can be classified as hypermutated, possessing hundreds to thousands of somatic mutations and including CRCs driven by defects in DNA mismatch repair and POLE mutations; and non-hypermutated, with tens of somatic mutations containing multiple copy number alterations and aneuploidy with oncogenic activation of KRAS and PIK3CA coupled with mutations and loss of heterozygosity of tumor suppressors APC and TP53. Epigenetic events as well as inflammatory-driven cellular alterations in DNA mismatch repair further contribute to CRC pathogenesis and metastasis. Because CRC is deadly, prevention through screening (and/or surveillance in high-risk patients) is an ideal and effective approach. Screening provides the opportunity to identify and remove the adenoma precursors before they can become CRC; it also can utilize the somatic genetic knowledge to effectively screen patients noninvasively. There are seven CRC screening tests suggested by the USPSTF and a Multi-society Task Force for effective screening, with varying abilities to detect significant colonic neoplasia and various specificities; even the most noninvasive and least sensitive test has shown a durable reduction in CRC mortality and is cost effective. Thus, any of the seven CRC screening tests is better than no test. Noninvasive strategies include guaiac-based fecal occult blood testing, fecal immunochemical testing, fecal DNA testing, and CT colonography. Luminal-invasive tests include flexible sigmoidoscopy and colonoscopy and their combinations with a noninvasive test. If any of the noninvasive tests shows a positive result, a colonoscopy should be performed to identify the cause of the positive test. For high-risk patients or the surveillance of patients, colonoscopy is the modality that should be used. Knowledge of the patient’s age and family history and personal adenoma or CRC history can influence when to commence screening; additionally, multiple lines of evidence suggest that race should be included in the algorithm influencing the timing and tempo of screening and/or surveillance. Citation Format: John M. Carethers. Colon cancer screening and genetics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY14-01. doi:10.1158/1538-7445.AM2017-SY14-01

Abstract 1759: Description of molecular marker disparities and KRAS mutational spectrum of colorectal tumors from Puerto Rican Hispanics

Abstract Colorectal cancer (CRC) causes 27% of all cancer deaths among Puerto Rican Hispanics (PRH). Most CRC cases are due to sporadic genetic or epigenetic events that lead to the development of the tumor. These events aggregate to cause CRC carcinogenesis and involve genes that regulate cell growth and differentiation. Improving understanding of the molecular events that lead to CRC carcinogenesis has the potential to reduce CRC mortality by risk stratifying individuals as well as developing prevention strategies. Currently, there are a set of molecular markers that are used to characterize CRC tumors and inform prognosis and treatment decisions. These markers include: microsatellite instability (MSI), CpG island methylation and mutational analysis of the KRAS and BRAF oncogenes. The objective of this study was to characterize the molecular markers present in the CRC tumors of PRH and understand the disparities present at the molecular level in these tumors. The frequency of the MSI and CIMP were evaluated in 488 CRC tumors from PRH. Mutations in the KRAS gene and the BRAF V600E mutation were evaluated using SuperArray technology. Additionally, information regarding sociodemographic and clinicopathologic characteristics of the study population was obtained. Of the 488 evaluated CRC tumors 1.6% (n=2) showed MSI and 90.2% of the studied tumors had CIMP low phenotype (n=102). MSI-High tumors were more likely to be distal tumors compared to MSS tumors (p=0.02). The V600E mutation in the BRAF gene were found in 9.17% (n=11) of the studied tumors. KRAS mutations were found in 31.25% (n=40) of tumors. The most common KRAS mutations found in the CRC tumors of PRH were: c.35G>A (KRAS COSMIC521) (n=12) and c.38G>A (n=8) (KRAS COSMIC532). Furthermore, the traditional CRC carcinogenesis pathway was the predominant pathway observed for the development of the CRC tumors of our study population. The following study highlights a distinct molecular signature for the CRC tumors from PRH descent. The disparities observed in the prevalence of the molecular markers (low MSI, CIMP Low and mainly wild-type for KRAS and BRAF) suggest that the drivers for CRC in this population might differ from other populations. Additional studies are required to fully elucidate the CRC carcinogenesis pathway in PRH. Citation Format: Julyann Perez-Mayoral, Camila Rivera-Lynch, Marievelisse Soto-Salgado, Xavier Llor, Luis Tous-Lopez, Marla Torres-Torres, Jose S. Reyes, Carlos Torres, Ajay Goel, Segundo Rodriguez-Quillichini, Marcia Cruz-Correa. Description of molecular marker disparities and KRAS mutational spectrum of colorectal tumors from Puerto Rican Hispanics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1759. doi:10.1158/1538-7445.AM2017-1759

CMOST: an open-source framework for the microsimulation of colorectal cancer screening strategies

BackgroundColorectal cancer (CRC) is a leading cause of cancer-related mortality. CRC incidence and mortality can be reduced by several screening strategies, including colonoscopy, but randomized CRC prevention trials face significant obstacles such as the need for large study populations with long follow-up. Therefore, CRC screening strategies will likely be designed and optimized based on computer simulations. Several computational microsimulation tools have been reported for estimating efficiency and cost-effectiveness of CRC prevention. However, none of these tools is publicly available. There is a need for an open source framework to answer practical questions including testing of new screening interventions and adapting findings to local conditions.MethodsWe developed and implemented a new microsimulation model, Colon Modeling Open Source Tool (CMOST), for modeling the natural history of CRC, simulating the effects of CRC screening interventions, and calculating the resulting costs. CMOST facilitates automated parameter calibration against epidemiological adenoma prevalence and CRC incidence data.ResultsPredictions of CMOST were highly similar compared to a large endoscopic CRC prevention study as well as predictions of existing microsimulation models. We applied CMOST to calculate the optimal timing of a screening colonoscopy. CRC incidence and mortality are reduced most efficiently by a colonoscopy between the ages of 56 and 59; while discounted life years gained (LYG) is maximal at 49–50 years. With a dwell time of 13 years, the most cost-effective screening is at 59 years, at $17,211 discounted USD per LYG. While cost-efficiency varied according to dwell time it did not influence the optimal time point of screening interventions within the tested range.ConclusionsPredictions of CMOST are highly similar compared to a randomized CRC prevention trial as well as those of other microsimulation tools. This open source tool will enable health-economics analyses in for various countries, health-care scenarios and CRC prevention strategies. CMOST is freely available under the GNU General Public License at https://gitlab.com/misselwb/CMOST

Methanolic extract of Boswellia serrata exhibits anti-cancer activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells

BackgroundColorectal cancer (CRC) is the most common cancer. A proper method to reduce mortality of CRC is chemoprevention to prevent initiation and promotion of intestinal tumorgenesis. One of the promising and developing chemopreventive agents is natural compounds found in plants. Frankincense, the resin extract from the Boswellia specious, has been used in traditional and modern medicine for treating various diseases with very minimal side effects. In the current study, we investigated the anti-cancer activity of methanolic extract of Boswellia serrata (B. serrata) on HT-29 human colon cancer cells. MethodsHT-29 cells were treated with different concentrations of B. serrata and cell viability was assessed by MTT assay. mRNA expression of microsomal prostaglandin E synthase-1 (mPGES-1), vascular endothelial growth factor (VEGF), C-X-C chemokine receptor type 4 (CXCR4), matrix metalloproteinase-2 (MMP-2), MMP-9 and hypoxia-inducible factor-1 (HIF-1) were examined by quantitative real-time PCR. Apoptosis was evaluated by the proportion of sub-G1 cells. Prostaglandin E2 (PGE2) level and caspase 3 activity were determined by ELISA assay. Tube formation potential and HT-29 cells migration were assessed using three-dimensional vessel formation assay and scratch test. ResultsB. serrata extract considerably decreased the expression of mPGES-1, VEGF, CXCR4, MMP-2, MMP-9 and HIF-1. The caspase 3 activity and percent of cells in sub-G1 phase were increased by B. serrata extract. Cell viability, PGE2 generation, in vitro tube formation and cell migration were decreased significantly in B. serrata–treated HT-29 compared to the control group. ConclusionOur findings suggest that B. serrata extract inhibits proliferation, angiogenesis and migration and induces apoptosis in HT-29 cells by inhibiting of mPGES-1 and decreasing the PGE2 level and its downstream targets.

Tu1038 Limited Impact on CRC Detection and Mortality Rates With Complete Colonoscopy Examination Despite Poor Bowel Preparation

Tu1038 Limited Impact on CRC Detection and Mortality Rates With Complete Colonoscopy Examination Despite Poor Bowel Preparation

Colorectal cancer disparities among racial/ethnic minorities in Texas, 1995–2003

ABSTRACTColorectal cancer (CRC) interventions can be more precisely targeted geographically if locations of high-risk population groups can be detected and risk factors at these locations can be identified. This study aims to detect small geographic areas where CRC late-stage diagnosis and mortality rates were disproportionally high among racial/ethnic minorities (i.e., non-Hispanic African Americans and Hispanics) in Texas using non-Hispanic Whites as a reference group. The analysis used data about CRC cases diagnosed between 1995 and 2003 in Texas with follow-up data up to 2008. In addition, this study identifies neighborhood-level factors that are associated CRC mortality disparities in the identified geographic areas using a logistic regression analysis. Analysis results indicate that CRC mortality disparities existed in the Austin-San Antonio, the Dallas-Fort Worth, and the Houston metropolitan areas for both non-Hispanic African Americans and Hispanics. Additionally, for non-Hispanic African Americans, census tracts with significant CRC mortality disparities concentrated mostly in the eastern part of Texas. For Hispanics, census tracts with significant CRC mortality disparities scattered in different parts of Texas. Results from this study suggest that CRC intervention programs may benefit from providing additional assistance to African Americans and Hispanics with a low socioeconomic status in the identified areas.

Abstract IA09: Realizing the promise of prevention (at the personal and population levels)

Abstract IA09: Realizing the promise of prevention (at the personal and population levels)

Socioeconomic and ethnic inequities within organised colorectal cancer screening programmes worldwide

ObjectiveColorectal cancer (CRC) screening programmes can reduce CRC mortality. However, the implementation of a screening programme may create or exacerbate socioeconomic and ethnic health inequities if participation varies by subgroup....

Association of N-Linked Glycoprotein Acetyls and Colorectal Cancer Incidence and Mortality.

BackgroundAcute phase proteins highlight the dynamic interaction between inflammation and oncogenesis. GlycA, a novel nuclear magnetic resonance (NMR) inflammatory marker that identifies primarily circulating N-acetyl glycan groups attached to acute phase proteins, may be a future CRC risk biomarker.MethodsWe examined the association between GlycA and incident CRC and mortality in two prospective cohorts (N = 34,320); Discovery cohort: 27,495 participants from Women's Health Study (WHS); Replication cohort: 6,784 participants from Multi-Ethnic Study of Atherosclerosis (MESA). Multivariable Cox models were adjusted for clinical risk factors and compared GlycA to acute phase proteins (high-sensitivity C-reactive protein [hsCRP], fibrinogen, and soluble intercellular adhesion molecule-1 [sICAM-1]).ResultsIn WHS (median follow-up 19 years, 337 cases, 103 deaths), adjusted HRs (95% CIs) per SD increment of GlycA for CRC incidence and mortality were 1.19 (1.06–1.35; p = 0.004) and 1.24 (1.00–1.55; p = 0.05), respectively. We replicated findings in MESA (median follow-up 11 years, 70 cases, 23 deaths); HRs (95% CIs) per SD of GlycA for CRC incidence and mortality were 1.32 (1.06–1.65; p = 0.01) and 1.54 (1.06–2.23; p = 0.02), respectively, adjusting for age, sex, and race. Pooled analysis, adjusted HR (95% CI) per SD of GlycA for CRC incidence and mortality was 1.26 (1.15–1.39; p = 1 x 10−6). Other acute phase proteins (hsCRP, fibrinogen, and sICAM-1) had weaker or no association with CRC incidence, while only fibrinogen and GlycA were associated with CRC mortality.ConclusionsThe clinical utility of GlycA to personalize CRC therapies or prevention warrants further study.Trial RegistrationClinicalTrials.gov: WHS NCT00000479, MESA NCT00005487

Prevention of Colorectal Neoplasia

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide. There are well-established screening protocols involving fecal testing, radiographic, and endoscopic evaluations that have led to decreased incidence and mortality of CRC in the United States. In addition to screening for CRC, there is interest in preventing colorectal neoplasia by targeting the signaling pathways that have been identified in the pathway of dysplasia progressing to carcinoma. This review will detail the efficacy of multiple potential preventative strategies including lifestyle changes (physical activity, alcohol use, smoking cessation, and obesity); dietary factors (dietary patterns, calcium, vitamin D, fiber, folate, and antioxidants and micronutrients); and chemopreventive agents (nonsteroidal anti-inflammatory drugs, statins, metformin, bisphosphonates, and postmenopausal hormonal therapy).