Colorectal Cancer Rates Research Articles

Expert consensus on the optimal management of BRAFV600E-mutant metastatic colorectal cancer in the Asia-Pacific region.

The burden of colorectal cancer (CRC) is high in the Asia-Pacific region, and several countries in this region have among the highest and/or fastest growing rates of CRC in the world. A significant proportion of patients will present with or develop metastatic CRC (mCRC), and BRAFV600E-mutant mCRC represents a particularly aggressive phenotype that is less responsive to standard chemotherapies. In light of recent therapeutic advances, an Asia-Pacific expert consensus panel was convened to develop evidence-based recommendations for the diagnosis, treatment, and management of patients with BRAFV600E-mutant mCRC. The expert panel comprised nine medical oncologists from Australia, Hong Kong, Singapore, and Taiwan (the authors), who met to review current literature and develop eight consensus statements that describe the optimal management of BRAFV600E-mutant mCRC in the Asia-Pacific region. As agreed by the expert panel, the consensus statements recommend molecular testing at diagnosis to guide individualized treatment decisions, propose optimal treatment pathways according to microsatellite stability status, advocate for more frequent monitoring of BRAFV600E-mutant mCRC, and discuss local treatment strategies for oligometastatic disease. Together, these expert consensus statements are intended to optimize treatment and improve outcomes for patients with BRAFV600E-mutant mCRC in the Asia-Pacific region.

Assessing the Impact of Serum Calcium, 25-Hydroxy Vitamin D, Ferritin, and Uric Acid Levels on Colorectal Cancer Risk.

The aim of this study is to investigate whether vitamin D, calcium, ferritin, and uric acids play a beneficial biomarker role in the prevention of colorectal cancer (CRC) risk. The case-control design was employed, including 650 CRC cases and 650 controls aged 35 to 70 years, comprising both men and women. The study encompasses sociodemographic data, clinical information, radiological diagnoses, and biochemical measurements. Statistically significant differences were observed between CRC and controls in terms of age, diagnostic radiology, tomography, positron emission tomography/computed tomography (PET/CT), colonoscopy, CRC awareness, risk factors, age, genetics, exposure to chemicals, inadequate nutrition, smoking, hookah and alcohol use. Significant differences were also identified in intestinal inflammations, obesity, processed foods (P < 0.001), abdominal pain and cramps, diarrhea, constipation, blood in stool, bloating (gas), irritable bowel, nausea/vomiting, anemia, stress, fatigue, weakness, and weight loss. Regarding biochemical parameters, statistically significant differences were found between CRC and controls in terms of hemoglobin, glycated hemoglobin (HbA1c), fasting blood glucose (FBG), vitamin D, neutrophil level, red blood cell (RBC), white blood cell (WBC), platelet level, platelet count, hematocrit, potassium, sodium (Na), calcium, creatinine, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), bilirubin, uric acid, iron (Fe), ferritin, C-reactive protein (CRP), total protein, systolic blood pressure (SBP), and diastolic blood pressure (DBP) parameters (P < 0.001). Multivariate stepwise regression analysis was performed to find the best risk factors for the diagnosis of CRC as the dependent variable. As a result of the analysis, intestinal inflammation (P < 0.001), nausea/vomiting (P < 0.001), stomach pain (P = 0.003), hookah-smoking (P = 0.034), uric acid (P < 0.001), bilirubin (P < 0.001), cigarette smoke exposure (P = 0.033), processed food consumption (P = 0.002), calcium levels (P = 0.029), vitamin D deficiency (P < 0.001), and ferritin (P < 0.001) levels were identified as significant determinants for CRC. The current study demonstrated that vitamin D, calcium, ferritin, and uric acids play a beneficial biomarker role in reducing the risk of CRC prevention. The increase in CRC rates may be associated with lifestyle, environmental and hereditary factors, nutrition, alcohol consumption, hookah use, and cigarette smoking.

Enhancing colorectal cancer screening in high-risk population through fecal immunochemical test surveillance: Results from a surveillance program.

Current guidelines recommend colonoscopy-based surveillance to decrease the risk of colorectal cancer (CRC) among these participants with above-average risk. The fecal immunochemical test (FIT) holds promise as a viable alternative surveillance tool, but the existing evidence regarding the use of settings remains limited. Therefore, our aim is to evaluate the CRC incidence rates in individuals with above-average CRC risk and the relationship between FIT surveillance and CRC incidence. The retrospective cohort study was performed based on the CRC screening program between January 2012 and December 2022, in Tianjin, China. This cohort study included 12,515 participants aged 40-74 years with above-average risk. The primary outcomes were the incidence rates of CRC and advanced colorectal neoplasia which were expressed as the number of events per 100,000 person-years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. We included 12,515 participants aged 40-74 years, of whom 4980 received subsequent FIT surveillance during the study period. Among these participants, 51 CRC cases occurred in the non-FIT surveillance group (incidence rate, 233.88 per 100,000 person-years) and there were 29 cases of CRC in the FIT surveillance group (incidence rate, 184.85 per 100,000 person-years), resulting in an incidence rate ratio (IRR) of 0.58 (95% CI, 0.37-0.91). Meanwhile, 428 advanced colorectal neoplasia cases were reported in the non-FIT surveillance group, while 269 cases occurred in the FIT surveillance group, with significantly lower incidence of advanced colorectal neoplasia in the FIT surveillance group (IRR: 0.64; 95% CI, 0.55-0.74). Compared with the non-FIT surveillance group, the FIT surveillance group had a 54% decreased risk of developing CRC (HR, 0.46; 95% CI, 0.29-0.74) and a 45% decreased risk of developing advanced colorectal neoplasia (HR, 0.55; 95% CI, 0.47-0.64). In this retrospective cohort study, above-average risk individuals who received subsequent FIT in the intervals between colonoscopies were associated with a reduction of CRC and advanced colorectal neoplasia incidence, which indicated the value and utility of FIT in the surveillance program.

Predicting the risk of colorectal cancer among diabetes patients using a random survival forest-guided approach.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide. Diabetes and CRC share many overlapping lifestyle risk factors such as obesity, heavy alcohol use, and diet. This study aims to develop a risk scoring system for CRC prediction among diabetes patients using routine medical records. A retrospective cohort study was conducted using electronic health records of Hong Kong. Patients who received diabetes care in public general outpatient clinics between 2010 and 2019 and had no cancer history were identified, and followed up until December 2019. The outcome was diagnosis of CRC during follow-up. For model building, predictors were first selected using random survival forest, and weights were subsequently assigned to selected predictors using Cox regression. Of the 386,325 patients identified, 4,199 patients developed CRC during a median follow-up of 6.2 years. The overall incidence rate of CRC was 1.93 per 1000 person-years. In the final scoring system, age, waist-to-hip ratio, and serum creatinine were included as predictors. The C-index on test set was 0.651 (95%CI: 0.631-0.669). Elevated serum creatinine (≥127 µmol/L) could be a potential important predictor of increased CRC risk. While obesity is a well-known risk factor for CRC, renal dysfunction could be potentially linked to an elevated risk of CRC among diabetes patients. Further studies are warranted to explore whether renal function could be a potential parameter to guide screening recommendation for diabetes patients.

Therapeutic efficacy of ferroptosis in the treatment of colorectal cancer (Review).

Colorectal cancer (CRC) is the third most common malignancy worldwide, and the second leading cause of cancer-associated mortality. The incidence and mortality rates of CRC remain high, posing a significant threat to humans and overall quality of life. Current therapeutic strategies, such as surgery and chemotherapy, are limited due to disease recurrence, chemotherapeutic drug resistance and toxicity. Thus, research is focused on the development of novel treatment approaches. In 2012, ferroptosis was identified as a form of regulated cell death that is iron-dependent and driven by lipid peroxidation. Notably, therapies targeting ferroptosis exhibit potential in the treatment of disease; however, their role in CRC treatment remains controversial. The present study aimed to systematically review the mechanisms and signaling pathways of ferroptosis in CRC, and the specific role within the tumor microenvironment. Moreover, the present study aimed to review the role of ferroptosis in drug resistance, offering novel perspectives for the diagnosis and treatment of CRC.

Abstract A080: Improving outcomes: Addressing racial and ethnic disparities in colorectal cancer genomic research

Abstract Colorectal cancer (CRC) is the fourth most common cancer diagnosed in the United States (U.S.). This disease presents notable health disparities among racial and ethnic minorities in the U.S. Native Americans (NA) and non-Hispanic Blacks (NHB) exhibit the highest incidence and mortality rates for CRC compared to non-Hispanic Whites (NHW). These disparities are driven by a combination of factors, including socioeconomic inequalities, access to healthcare, lifestyle habits, and genetic susceptibilities. Minority populations often face delays in diagnosis and treatment, leading to advanced disease stages at presentation and poorer outcomes. Addressing these disparities through cancer genomics is essential for developing effective, personalized treatments that can improve outcomes for underrepresented populations. Comprehensive genomic studies can reveal genetic mutations and biomarkers unique to these groups, facilitating targeted therapies and preventive measures tailored to their specific needs. To address these disparities, we conducted an analysis of U.S. population-based colorectal cancer studies within 3 cancer genomic databases: the National Cancer Institute’s Genomic Data Commons, the AACR Project GENIE, and cBioPortal. We identified 13 studies suitable for inclusion, calculating incidence percentages across all racial and ethnic categories. Our analysis encompassed a total of 20,295 patients. Among the analyzed patients, the racial distribution was as follows: NHW (68.5%), Asians (5.30%), NHB (7.7%), Other (5.6%), NA (0.2%), Pacific Islander/Native Hawaiian (0.07%), and not reported (12.7%). Ethnic data was missing for 24.1% (n=4,895) of the patients. Samples were predominantly from individuals identified as Not Hispanic (68.4%), while Hispanic individuals constituted 7.5%. Our results show significant underrepresentation of NHB, NA and Hispanic patients in CRC genomic databases highlighting a disparity between expected and actual representation. These findings underscore the critical need for inclusive research practices. Addressing these disparities in cancer genomics is imperative to develop equitable, effective treatments and improve health outcomes for all populations. Ensuring diverse representation in genomic databases will enhance the understanding of genetic differences across populations, inform targeted therapies, and ultimately contribute to reducing CRC disparities. By addressing these disparities, we can move towards a future where all populations benefit equally from advancements in CRC treatment and prevention, thus improving survival rates and quality of life for minority groups. Citation Format: Gabriela Arroyo Figueroa, Tim F. Greten, Cecilia Monge. Improving outcomes: Addressing racial and ethnic disparities in colorectal cancer genomic research [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A080.

Association of late eating with colorectal adenomas: a cross-sectional study.

Colorectal cancer (CRC) is linked to lifestyle exposures. However, changes in the CRC rates among younger populations remain poorly understood and suggest the existence of yet unidentified factor(s) that may contribute to colon carcinogenesis. Here, we investigated the potential role of time of eating in the risk of pre-cancerous colonic neoplasms (tubular adenoma: TA). We enrolled 663 participants undergoing screening colonoscopies. Data on food timing, dietary intake, sleep/wake patterns, and chronotype were collected through structured questionnaires. Late eating was defined as the consumption of food or snack within a 3-hour window of sleep onset for at least four days a week. Pathology reports confirmed the histology of colonic polyps, and adenomas were further classified into risk categories. A total of 644 patients met criteria for our study. There were 270 (42.2%) participants classified as late eaters. Compared to non-late eaters, the odds of TA were higher in late eaters (OR = 1.46, 95% CI = 1.05-2.03, p = 0.023), an association which was strengthened after adjusting for multiple confounders (OR 1.98, 95% CI 1.19-3.28, p = 0.008). Late eating remained an independent risk factor for high-risk as well as multiple TAs. This study proposes late eating as a risk factor for colon tubular adenomas and underscores the potential role of less studied forms of circadian disruption imposed by time of eating in the development of colon neoplastic formation.

Clinical significance of peripheral blood UL16 and DR-70 for the early diagnosis and prognostic evaluation of colorectal cancer.

Early diagnosis of colorectal cancer (CRC) is of great significance to improve the survival rate and quality of life of patients, but early diagnosis of CRC requires more sensitive techniques. Peripheral blood UL16-binding protein 2 (ULBP2) and human fibrinogen degradation products (DR-70) are the main indicators for the diagnosis of malignant tumors. To assess ULBP2 and DR-70 potential for the early diagnosis and prognostic evaluation of CRC to provide a reference. This study involved 60 patients with early-stage CRC (CRC group), 50 patients with benign colorectal tumors (benign group), and 50 healthy patients (control group) enrolled at the Affiliated Hospital of Jiangnan University and Jiangsu Province Official Hospital between January, 2020 and January, 2022. ULBP2 and DR-70 levels in the blood were determined and differences among the three groups and early diagnostic values for CRC were determined. Patients with CRC were divided into the good prognosis and poor prognosis groups, and ULBP2 and DR-70 levels in the blood and diagnostic values were compared. ULBP2 and DR-70 serum levels were significantly higher in the CRC group than in the control and benign groups (P < 0.05); however, no significant differences were observed between the benign and control groups (P > 0.05). Among the 60 patients with CRC followed up for two years, two died (3.33%) and 15 exhibited tumor metastasis, progression, or recurrence (25.00%). ULBP2 and DR-70 serum levels were significantly higher in the poor prognosis group than in the good prognosis group (P < 0.05). A receiver operating characteristic curve was plotted. Area under the curve, sensitivity, and specificity of serum ULBP2 with DR-70 for the early diagnosis of CRC were higher than those of the single serum indices (P < 0.05) in both the good and poor prognosis groups. ULBP2 and DR-70 serum levels were significantly high in patients with early-stage CRC. They improved the diagnostic rate of early-stage CRC and predicted patient prognosis, thereby showing clinical application potential.

Challenges around diagnosis of early onset colorectal cancer, and the case for screening.

Colorectal cancer (CRC) is the third most diagnosed cancer in the world, with an estimated 1.93 million cases diagnosed in 2020. While the overall CRC incidence in many countries is falling there has been a dramatic increase in CRC in those aged under 50 (early onset colorectal cancer, EOCRC). The reason for this increase in EOCRC is unknown. As the best predictor of survival is stage at diagnosis, early diagnosis is likely to be beneficial and population screening may facilitate this. A narrative review of the literature was undertaken. Improving time to diagnosis in symptomatic patients is beneficial. However, by the time symptoms develop, over a third of patients already have metastatic disease. Screening asymptomatic patients (with Faecal Immunochemical test (FIT) and colonoscopy) has been proved to be effective in older patients (>60 years). In younger populations, the decreasing incidence rates of CRC previously made cost effectiveness, compliance and therefore benefit questionable. Now, with the increasing incidence of CRC in those under 50 years of age, modelling suggests screening with FIT and colonoscopy is cost effective from 40 years of age. There is evidence that some countries screening below 50 have prevented the rise in EOCRC incidence. Additionally the use of new and novel non-invasive biomarkers may also be able to improve the accuracy of screening asymptomatic patients. Diagnosis of EOCRC once symptoms develop is often too late, and screening patients from age 40 is the best way to improve outcomes in this group.

Pattern of Colorectal Cancer in Karbala Province of Iraq: Data from Developing Country

Background: Globally, there are differences in the prevalence of colorectal cancer (CRC) depending on environmental and demographic factors. Objective: Our study’s objective was to analyze the CRC pattern in the Iraqi province of Karbala, comparing and identifying probable variations with another people. Methods: In Iraq, at the Al-Hussein Cancer Center in Karbala, retrospective descriptive research was conducted on 524 patients who diagnosed with CRC from January 2012 to December 2020. Results: The incidence rate of CRC increased from 3.83 per 100,000 in 2012 to 5.69 per 100,000 in 2020. Among our patients, median age was 55 years. The proportion of males was (54.96%) while the proportion of females was (45.04%) with a M:F ratio of (1.22:1). The most affected anatomical site was colon in (64.89%) and adenocarcinoma was the most frequent histopathology in (67.18%). Unfortunately, more than 46% of cases presented as stage III &amp; IV. Conclusion: This statistical analysis of CRC could be a fundamental knowledge source to analyze epidemiological pattern, to assess development in the last few years and to improve treatment plans.

The gut barrier as a gatekeeper in colorectal cancer treatment.

Colorectal cancer (CRC) is highly prevalent and is a major cause of cancer-related deaths worldwide. The incidence rate of CRC remains alarmingly high despite screening measures. The main curative treatment for CRC is a surgical resection of the diseased bowel segment. Postoperative complications usually involve a weakened gut barrier and a dissemination of bacterial proinflammatory lipopolysaccharides. Herein we discuss how gut microbiota and microbial metabolites regulate basal inflammation levels in the gut and the healing process of the bowel after surgery. We further elaborate on the restoration of the gut barrier function in patients with CRC and how this potentially impacts the dissemination and implantation of CRC cells in extracolonic tissues, contributing therefore to worse survival after surgery.

The repeat FIT (RFIT) study: Does repeating faecal immunochemical tests provide reassurance and improve colorectal cancer detection?

Faecal immunochemical tests (FIT) are highly sensitive for colorectal cancer (CRC) detection. Little evidence exists regarding repeat FIT. The repeat FIT (RFIT) study aimed to determine whether second and third FIT provide reassurance and improve CRC or significant bowel disease (SBD) identification. This was a prospective observational study. Patients recruited from urgent referrals returned three FIT and underwent colonoscopy. Chi-square tests compared categorical data. Diagnostic accuracy variables (sensitivity/specificity/positive predictive value [PPV]/negative predictive value [NPV]) were calculated for one, two and three FIT (95% CI). Three negative FIT (<10 μg Hb/g of faeces [μg/g]) groups (one, two, three) were compared with positive groups (one or more FIT ≥10 μg/g). CRC and SBD detection rates were compared by strategy. A total of 460 patients (mean age: 66.8 years, 233 males and 227 females, 23 CRC, 80 SBD) were included in the study. For one, two and three negative FIT, CRC sensitivity remained static (95.7%); specificity (44.6%, 40.7% and 38.4%) and NPV decreased (99.5%, 99.4% and 99.4%). For SBD, sensitivity increased (78.8%, 83.8% and 86.3%), specificity decreased (47.4%, 43.7% and 41.6%) and NPV increased (91.4%, 92.7% and 93.5%). In one, two and three positive FIT groups, CRC detection was 8.3%,16.1% and 20.9%. CRC mean FIT was 150 μg/g, <6 μg/g for benign pathology. One or more negative FIT increases the sensitivity for CRC/SBD. Repeating FIT provides greater differentiation of patients with and without CRC/SBD compared to single FIT but is associated with decreased specificity and PPV. Multiple negative FIT may offer reassurance; however, application of repeating FIT may be restricted given the associated increase in investigations S1.

Screening and Surveillance of Colorectal Cancer: A Review of the Literature.

Colorectal cancer (CRC) has the highest mortality rate among men and is the second highest among women under fifty, with incidence and mortality rates rising in younger populations. Studies indicate that up to one-third of patients diagnosed before fifty have a family history or genetic factors, highlighting the need for earlier screening. Contrariwise, diagnosis in healthy subjects through screening strategies enables early-stage detection of the tumor and better clinical outcomes. In recent years, mortality rates of CRC in Western countries have been on a steady decline, which is largely attributed to widespread screening programs and advancements in treatment modalities. Indeed, early detection through screening significantly improves prognosis, with stark differences in survival rates between localized and metastatic disease. This article aims to provide a comprehensive review of the existing literature, delving into the performance and efficacy of various CRC screening strategies. It navigates through available screening tools, evaluating their efficacy and cost-effectiveness. The discussion extends to delineating target populations for screening, emphasizing the importance of tailored approaches for individuals at heightened risk.

Epidemiology of Colorectal Cancer in Saudi Arabia: A Review.

Colorectal cancer (CRC) is the second leading cause of cancer death in the world, originating from the glandular epithelial cells of the large intestine and the rectum. This article aims to review the epidemiology of CRC in Saudi Arabia, focusing on prevalence, incidence, risk factors, preventive measures, and outcomes. This narrative review utilized the PubMed database for data extraction, including freely accessible studies published in the last 15 years. Sixteen articles from different study designs were included, while awareness and non-English language studies were excluded. In 2020, the incidence and mortality rate of CRC in Saudi Arabia were 14.6% and 1.48% among all cancers, respectively. From 2006 to 2016, the number of colon cancer and rectal cancer cases increased by 8% and 7%, respectively. Risk factors for CRC in Saudi Arabia include low education level, unemployment, physical inactivity, excess weight, poor knowledge of foods rich in fiber, cigarette smoking, reduced serum vitamin D and calcium levels, and certain gene mutations. National guidelines in Saudi Arabia recommend CRC screening for all individuals above 45 years using colonoscopy, flexible sigmoidoscopy, or fecal occult blood test. The 10-year survival rate for CRC in Saudi Arabia is 44.6%. The overall 5-year survival rate for the Ministry of National Guard-Health Affairs is 52.0%. To lower the incidence and mortality of CRC, primary, secondary, and tertiary prevention are all very important. The most crucial aspect is to concentrate on primary prevention, which may involve raising public awareness of CRC risk factors and strategies for reducing or eliminating them.

Colorectal cancer screening: Modalities and adherence

In the last decade, several studies have explored various modalities and strategies for colorectal cancer (CRC) screening, taking into account epidemiological data, individual characteristics, and socioeconomic factors. In this editorial, we comment further on a retrospective study by Agatsuma et al published in the recent issue of the World Journal of Gastroenterology . Our focus is on screening trends, particularly in relation to efforts to improve the currently suboptimal uptake among the general population worldwide, aiming to enhance early diagnosis rates of CRC. There is a need to raise awareness through health edu-cation programs and to consider the use of readily available, non-invasive screening methods. These strategies are crucial for attracting screen-eligible populations to participate in first-line screening, especially those in high- or average-risk groups and in regions with limited resources. Liquid biopsies and biomarkers represent rapidly evolving trends in screening and diagnosis; however, their clinical relevance has yet to be standardized.

Link between irritable bowel syndrome, depression, and colorectal cancer risk in young patients: Age-matched nationwide population-based study.

There exists a link between irritable bowel syndrome (IBS) and depression. Similarly, chronic depression is known to increase the risk of cancer in general. In this population-based analysis, we investigated the prevalence and the odds of colorectal cancer (CRC) in young-depressed patients with IBS. To investigate the relationship between IBS and CRC in young, depressed patients using a nationally representative United States inpatient sample. The 2019 National Inpatient Sample was used to identify young (18-44 years) patients admitted with comorbid depression in the presence vs absence of IBS using relevant International Classification of Diseases, Tenth Revision, Clinical Modification codes. Primary endpoint was the prevalence and odds of CRC in age matched (1:1) young-depressed cohort hospitalized with IBS (IBS+) vs without IBS (IBS-). Multivariable regression analysis was performed adjusting for potential confounders. Age-matched (1:1) young-depressed IBS+ (83.9% females, median age 36 years) and IBS- (65.8% females, median age 36 years) cohorts consisted of 14370 patients in each group. IBS+ cohort had higher rates of hypertension, uncomplicated diabetes, hyperlipidemia, obesity, peripheral vascular disease, chronic obstructive pulmonary disease, hypothyroidism, prior stroke, prior venous thromboembolism, anxiety, bipolar disorder, and borderline personality disorder (P < 0.005) vs the IBS- cohort. However, prior myocardial infarction, acquired immunodeficiency syndrome, dementia, smoking, alcohol abuse, and drug abuse (P < 0.005) are high in IBS- cohort. The rate of CRC was comparable in both cohorts [IBS+ n = 25 (0.17%) vs IBS- n = 35 (0.24%)]. Compared to the IBS- cohort, the odds ratio (OR) of developing CRC was not significantly higher [OR 0.71, 95% confidence interval (CI) 0.23-2.25)] in IBS+ cohort. Also, adjusting for baseline sociodemographic and hospital characteristics and relevant comorbidities, the OR was found to be non-significant (OR 0.89, 95%CI 0.21-3.83). This nationwide propensity-matched analysis revealed comparable prevalence and risk of CRC in young-depressed patients with vs without IBS. Future large-scale prospective studies are needed to evaluate the long-term effects of depression and its treatment on CRC risk and outcomes in IBS patients.

Regulator of G protein signaling 16 restrains apoptosis in colorectal cancer through disrupting TRAF6-TAB2-TAK1-JNK/p38 MAPK signaling

Colorectal cancer (CRC) remains a major global cause of cancer-related mortality, lacking effective biomarkers and therapeutic targets. Revealing the critical pathogenic factors of CRC and the underlying mechanisms would offer potential therapeutic strategies for clinical application. G protein signaling (RGS) protein family modulators play essential role within regulating downstream signaling of GPCR receptors, with function in cancers unclear. Our study focused on the expression patterns of RGS proteins in CRC, identifying Regulator of G protein signaling 16 (RGS16) as a prospective diagnostic and therapeutic target. Analyzing 899 CRC tissues revealed elevated RGS16 levels, correlating with clinicopathological features and CRC prognosis by immunohistochemistry (IHC) combined with microarray. We confirmed the elevated RGS16 protein level in CRC, and found that patients with RGS16-high tumors exhibited decreased disease-specific survival (DSS) and disease-free survival (DFS) compared to those with low RGS16 expression. Functional assays demonstrated that RGS16 promoted the CRC progression, knockdown of RGS16 led to significantly increased apoptosis rates of CRC in vitro and in vivo. Notably, we also confirmed these phenotypes of RGS16 in organoids originated from resected primary human CRC tissues. Mechanistically, RGS16 restrained JNK/P38-mediated apoptosis in CRC cells through disrupting the recruitment of TAB2/TAK1 to TRAF6. This study provides insights into addressing the challenges posed by CRC, offering avenues for clinical translation.

Does a "Western Lifestyle" Confer a Higher Burden of Colorectal Cancer? A Comparison of EU15+ Countries versus Global Trends between 1990 and 2019.

The incidence of colorectal cancer (CRC) in the U.S. is declining in adults 50 years and older; however, recent studies suggest an increasing disease burden among adults under age 50. This study aims to compare the incidence, mortality, and mortality-to-incidence ratios (MIRs) of CRC in EU15+ countries to determine if similar age-stratified occurrences are observed across these countries with similar "Western lifestyle"-related risk factors. Incidence and mortality rates for CRC between 1990 and 2019 were extracted using the Global Burden of Disease database. The data were age-stratified into groups between ages 25-49, 50-69, and greater than 69 years. We observed that the incidence of CRC increased globally for all age groups, with the highest increase observed for males (75.9%) and females (27.7%) aged 25-49. A similar trend was observed in 15 of the 19 EU15+ countries for males and 16 of the 19 EU15+ countries for females aged 25-49. Global mortality rates decreased for all age groups in females but increased for males in all age groups. This raises concerns regarding potentially modifiable risk factors contributing to increased CRC development and underscores the importance of implementing standardized screening at an earlier stage to ensure adequate detection in the younger population.

Modelling the impact of bias in fecal immunochemical testing on long-term outcomes of colorectal cancer screening

BackgroundAs the impact of unmanaged bias (i.e. systematic source of inaccuracy) in fecal immunochemical test (FIT) analytical performance on long-term colorectal cancer (CRC) outcomes is unknown, we assessed the impact bias in FIT performance in an ongoing FIT-based CRC screening program. MethodsThis study consisted of two parts: cross-sectional observational data analysis to estimate change in short-term outcomes and microsimulation modelling to estimate change in long-term outcomes assuming different levels of bias by assuming 15 % lower up to 15 % higher Hemoglobin detected in the stool compared to observed. Two scenarios were considered: bias occurring 1) one-time only, due to the occasional bias associated with the FIT kits used in 2020 and 2) consistently due to a constant bias associated with the FIT kits used from 2020 onwards. ResultsWith a hypothetical bias of −15 % to +15 %, we observed a positivity rate ranging from 6.7 % to 7.8 %, and a detection rate for CRC between 0.65 % and 0.68 %. Single biases in FIT performance resulted in less than 0.1 % change in long-term CRC screening outcomes, while consistent biases resulted in a much larger change (up to 1.4 % in CRC cases and CRC-related deaths and up to 2.07 % in total costs). Detecting lower Hemoglobin concentrations resulted in a relatively larger change on long-term CRC outcomes in comparison to positive bias. ConclusionsBecause of the substantial impact of consistent FIT bias, it is important to set evidence-based acceptance criteria of bias on long-term CRC screening outcomes and in particular, the introduction of an asymmetrical or upward shifted tolerance interval for FIT bias.

Development and evaluation of a risk prediction tool for risk-adapted screening of colorectal cancer in China

Risk prediction tools for colorectal cancer (CRC) have potential to improve the efficiency of population-based screening by facilitating risk-adapted strategies. However, such an applicable tool has yet to be established in the Chinese population. In this study, a risk score was created using data from the China Kadoorie Biobank (CKB), a nationwide cohort study of 409,854 eligible participants. Diagnostic performance of the risk score was evaluated in an independent CRC screening programme, which included 91,575 participants who accepted colonoscopy at designed hospitals in Zhejiang Province, China. Over a median follow-up of 11.1 years, 3136 CRC cases were documented in the CKB. A risk score was created based on nine questionnaire-derived variables, showing moderate discrimination for 10-year CRC risk (C-statistic = 0.68, 95 % CI: 0.67–0.69). In the CRC screening programme, the detection rates of CRC were 0.25 %, 0.82 %, and 1.93 % in low-risk (score <6), intermediate-risk (score: 6–19), and high-risk (score >19) groups, respectively. The newly developed score exhibited a C-statistic of 0.65 (95 % CI: 0.63–0.66), surpassing the widely adopted tools such as the Asia-Pacific Colorectal Screening (APCS), modified APCS, and Korean Colorectal Screening scores (all C-statistics = 0.60). In conclusion, we developed a novel risk prediction tool that is useful to identify individuals at high risk of CRC. A user-friendly online calculator was also constructed to encourage broader adoption of the tool.