Differences In Colorectal Cancer Research Articles

Colorectal Cancer Screening in Castilla La Mancha, Spain: The Influence of Social, Economic, Demographic and Geographic Factors

Colorectal cancer (CRC) is a health problem with a significant social impact, accounting for 700,000 deaths a year globally. CRC survival rates are increasing as a result of early detection and improvements in society and labor conditions. Differences in CRC have been found depending on place of residence (urban or rural), socioeconomic situation and unemployment, although studies in this regard are limited. The aims of the present study were to determine whether differences exist in diagnostic delay according to place of residence, to analyze the association between socioeconomic level and colonoscopy results and to evaluate CRC risk according to place of residence, income level and unemployment. Retrospective, descriptive and observational study based on colonoscopies performed between May 2015 and November 2018, analyzing relationships between colonoscopy findings of a population screening program and various socioeconomic and demographic variables included in the study (sex, age, place of residence, average annual income, unemployment rate, etc.), and determining any association between such factors and related increases in adenocarcinoma risk. A total of 1422 patients were included in the study. The difference in participation according to sex was greater in rural population (63,4% men/36,6% women in rural areas, 58% men/42% women in urban areas). The mean delayed diagnosis was 59,26 days in both groups. Adenocarcinoma risk was 1.216 times higher in rural population. High-grade dysplasic lesions and adenocarcinoma were more common in municipalities with income < 9000€. However, advanced stage adenocarcinoma was higher in municipalities with income > 9000€. Adenocarcinoma risk was 1,088 times higher in municipalities with an unemployment rate of > 10%. Living in rural areas is not a barrier to access to health care, with no disadvantages identified regarding diagnosis and treatment, thanks to public health policies and the large number of small municipalities near the referral hospital in Cuenca.

The Role of IL-37 and IL-38 in Colorectal Cancer.

Colorectal cancer (CRC) is a major killer. Dysregulation of IL-37 and IL-38, both anti-inflammatory cytokines, is observed in auto-immune diseases. The precise regulatory mechanisms of IL-37/IL-38 during the development of CRC remains unclear, but chronic intestinal inflammation is involved in the carcinogenesis of CRC. Constitutive production of colonic IL-37 and IL-38 is substantially reduced in CRC, consistent with an inverse correlation with CRC differentiation. Reduced colonic IL-37 and IL-38 is relating to CRC invasion and distant metastasis, suggesting a protective role for IL-38 within the tumor micro-environment. IL-38 is reduced in right-sided CRC compared to left-sided CRC, which is in line with multiple risk factors for right-sided CRC, including the embryonic development of the colon, and genetic differences in CRC between these two sides. Finally, colonic IL-37 and tumor associated neutrophils (TAN) seem to be independent biomarkers of prognostic value, whereas colonic IL-38 seems to be a reliable and independent biomarker in predicting the 5-year survival post-surgery in CRC. However, there is room for improvement in available studies, including the extension of these studies to different regions/countries incorporating different races, evaluation of the role of multi-drug resistance, and different subsets of CRC. It would be useful to determine the kinetics of circulating IL-38 and its relationship with drug resistance/targeted therapy. The measurement of colonic IL-38 at the molecular and cellular level is required to explore the contribution of IL-38 pathways during the development of CRC. These approaches could provide insight for the development of personalized medicine.

Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis

BackgroundMolecular differences in colorectal cancer (CRC) are associated with the metastatic route. Patient survival is mainly driven by metastatic spread thus it is imperative to understand its key drivers to develop biomarkers for risk stratification, follow-up protocols and personalized therapy. Thus, this study aimed to identify genes associated with the metastatic route in CRC.Material and methodsCRC patients resected at our clinic from 2005 to 2014 and with a minimum 5-year follow-up were included in this analysis and grouped into CRC with hepatic (HEP), peritoneal (PER) or without distant metastases (M0), and HEP/PER. Firstly, tumor RNA of 6 patients each was isolated by microdissection from formalin-fixed paraffin-embedded specimens and analyzed by a NanoString analysis. Subsequently, these results were validated with immunohistochemistry and correlated to clinicopathological parameters in a larger collective of CRC patients (HEP n = 51, PER n = 44, M0 n = 47, HEP/PER n = 28).ResultsCompared to M0, HEP tumors showed 20 differentially expressed genes associated with epithelial-mesenchymal transition (EMT) and angiogenesis. Compared to M0, PER tumors had 18 differentially expressed genes. The finding of different gene signatures was supported by the multidimensional principal component clustering analysis. Tumor perforation did not influence the metastatic route. CIB1 was homogenously and significantly overexpressed in HEP compared to M0 (p < 0.001), but not in PER. Furthermore, immunohistochemical validation demonstrated that the mean CIB1 expression in HEP was 80% higher than in M0 (p < 0.001).ConclusionGene expression analysis revealed that CIB1 is significantly overexpressed in CRC leading to liver metastases compared to M0 and PER. Thus, the present results suggest that CIB1 may play a crucial role for hematogenous spread to the liver but not for peritoneal carcinomatosis. Consequently, CIB1 seems to be a promising prognostic marker and a potential tool for future targeted therapies as well as early diagnostics and follow-up.

Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer.

Simple SummaryColorectal cancer (CRC) has been divided into four consensus molecular subtypes (CMS) using the unsupervised clustering of bulk transcriptomic data. The CMS, which align with known biological differences in CRC, have helped address inter-tumor heterogeneity and have been shown to be predictive of survival. However, bulk tumors are comprised of a mix of tumor cells, non-tumor stroma, and immune cells, and the relative contributions of each are not accounted for in the current CMS classification system. Here, we build an algorithm to assign CMS classification to individual cells, which we apply to single cell RNAseq data to explore the impact of intra-tumor heterogeneity on CMS. We find that the number of stromal and immune cells present has a strong influence on the bulk CMS type and that clusters of tumor epithelial cells derived from single cell RNAseq do not align with CMS.The implications of intratumor heterogeneity on the four consensus molecular subtypes (CMS) of colorectal cancer (CRC) are not well known. Here, we use single-cell RNA sequencing (scRNASeq) to build an algorithm to assign CMS classification to individual cells, which we use to explore the distributions of CMSs in tumor and non-tumor cells. A dataset of colorectal tumors with bulk RNAseq (n = 3232) was used to identify CMS specific-marker gene sets. These gene sets were then applied to a discovery dataset of scRNASeq profiles (n = 10) to develop an algorithm for single-cell CMS (scCMS) assignment, which recapitulated the intrinsic biology of all four CMSs. The single-cell CMS assignment algorithm was used to explore the scRNASeq profiles of two prospective CRC tumors with mixed CMS via bulk sequencing. We find that every CRC tumor contains individual cells of each scCMS, as well as many individual cells that have enrichment for features of more than one scCMS (called mixed cells). scCMS4 and scCMS1 cells dominate stroma and immune cell clusters, respectively, but account for less than 3% epithelial cells. These data imply that CMS1 and CMS4 are driven by the transcriptomic contribution of immune and stromal cells, respectively, not tumor cells.

Demographic differences of colorectal cancer in the community and academic setting in patients over the age of 75 compared to those aged 50 to 75.

e15594 Background: The age of life expectancy in the United States is 78.9 years of age and continues to increase with the help of public health initiatives along with scientific and technological breakthroughs in medicine. However, colorectal cancer screening guidelines for those over age 75 are individualized and not recommended in those over 85. We aimed to investigate the demographic differences of colorectal cancer by sex and race in patients aged 75 vs those aged 50-75, in the community and academic practice. Methods: Data were analyzed from the National Cancer Database between 2010-2014. Results were divided into two categories (50-75 year old, &gt;75 year old) and included number of patients, sex and race. Patient characteristics were compared with Mann-Whitney U, Pearson’s Chi-square, and the Kaplan-Meier method. Data was further analyzed comparing sex and race using chi-square analysis. Results: 167, 059 patients were included in the analysis. 49,551 cases identified in the academic practice and 117, 508 in the community practice. In the academic practice, group A (age 50-75), 57.3% (20,810) were male vs. 42.7% (15,488) female. In community practice, group A, 56.5% (43, 915) were male vs 43.5% (33, 742) female (p-value &lt;0.05). Conversely, in the academic practice-group B (age &gt;75), 46.2% (6127) were male vs 53.8% (7126) female. In the community practice-group B, 55.3% (22,027) were female vs 44.7% (17,824) male; (p-value &lt;0.05).For Black patients, decline in cases is seen by age. In academic practice, 16.5% of cases were aged 50-75 vs. 11.9% over age 75. In community practice; 11.5% were aged 50-75 vs. 6.5%, p&lt;0.05). Comparatively there was an increase in cases in White patients by age diagnosed in academic and community practice; 77.5% vs 84.2 in 50-75 and 84.8 vs. 90.9% in &gt;75, respectively (p&lt;0.05). Conclusions: Women age &gt;75 comprised a statistically significant greater proportion of colorectal cancer cases compared to men age &gt;75 in both the community and academic setting. Contrary to established reports detailing higher incidence rates in males aged 50-75. Furthermore, there is an increase in cases with age in White patients in comparison with a decrease in cases in Black patients. These findings may suggest the need for a more universal and less individualized approach for individuals over age 75.

Differences in colorectal cancer (CRC) patients who did and did not undergo screening: Results from the 45 and Up Study cohort

BackgroundThe Australian National Bowel Cancer Screening Program is a free population-based screening program aiming to identify precancerous lesions and early colorectal cancer using faecal occult blood tests in average-risk Australians. The participation rate in people invited to screening was 42 % in 2017–2018, well below the 56.6 % target level. Increasing screening in high-risk groups; such as those with a subsequent diagnosis of colorectal cancer, will improve the efficiency of the program. MethodsPatients were participants in the Australian 45 and Up (cohort) study; aged 55 or 65 years between May 2006 and June 2008. Patients reported a history of colorectal cancer in their enrolment questionnaire and whether or not they had screened before diagnosis. Demographic, lifestyle, dietary and health related characteristics were compared between those who did and did not participate in screening. Results339 participants who self-reported having colorectal cancer were included. Participants who were female, overweight (≥ 25 kg/m2), consumed less than the recommended five servings of vegetables per day, consumed ≤ 14 standard drinks per week (compared to non-drinkers) or did not meet physical activity guidelines were significantly less likely to have participated in screening. ConclusionConsiderable investment has been placed in the National Bowel Cancer Screening Program and the focus now is on improving participation. Our study has taken a unique approach to identifying high-risk groups by exploring factors related to screening participation in colorectal cancer patients. These findings can further leverage the program by targeting high-risk populations to reduce the colorectal cancer burden in Australia.

Distinctive Clinico-Pathological Characteristics of Colorectal Cancer in Sabahan Indigenous Populations.

Background:Malaysia is an ethnically diverse nation, comprising Malay, Chinese, Indian and indigenous groups. However, epidemiological studies on colorectal cancer have mainly focused on the three main ethnic groups. There is evidence that the clinico-pathological characteristics of some cancers may differ in indigenous populations, namely that they occur earlier and behave more aggressively. We aimed to determine if there were similar differences in colorectal cancer, focusing on the indigenous populations of Sabah. Methods:Histopathological reports of all patients diagnosed with colorectal carcinoma from January 2012 to December 2016 from public hospitals in Sabah were retrieved from the central computerized database of the Pathology Department of Queen Elizabeth Hospital in Kota Kinabalu, Sabah. Supplementary data was obtained from patients’ case files from each hospital. Clinico-pathological data were analysed using the IBM SPSS Statistical Software Version 23 for Windows for descriptive statistics (mean, median, ASR, AR, relative risk) and inferential statistics (Chi square test). Results:A total of 696 patients met the inclusion criteria. The median age for colorectal cancer in Sabah was 62 years (95% CI 60.3 to 62.3), with an age specific incidence rate of 21.4 per 100 000 population. The age specific incidence rate in the indigenous populations was 26.6 per 100 000, much lower than the Chinese, at 65.0 per 100 000. The risk of colorectal cancer occurring before the age of 50 was three times higher in the indigenous population compared to the Chinese. The tumours were mainly left-sided (56.5%), adenocarcinoma in histology (98.4%) and moderately differentiated (88.7%). Approximately 79.2% of patients received curative treatment. Conclusion:Indigenous populations in Sabah develop colorectal cancer at an earlier age, and present at more advanced stages. This has implications for screening and therapeutic strategic planning.

Metabolic pathways in sporadic colorectal carcinogenesis: A new proposal

Given the reports made about geographical differences in Colorectal Cancer (CRC) occurrence, suggesting a link between dietary habits, genes and cancer risk, we hypothesise that there are four fundamental metabolic pathways involved in diet-genes interactions, directly implicated in colorectal carcinogenesis: folate metabolism; lipid metabolism; oxidative stress response; and inflammatory response. Supporting this hypothesis are the evidence given by the significant associations between several diet-genes polymorphisms and CRC, namely: MTHFR, MTR, MTRR and TS (involved in folate metabolism); NPY, APOA1, APOB, APOC3, APOE, CETP, LPL and PON1 (involved in lipid metabolism); MNSOD, SOD3, CAT, GSTP1, GSTT1 and GSTM1 (involved in oxidative stress response); and IL-1, IL-6, TNF-α, and TGF-β (involved in inflammatory response). We also highlight the association between some foods/nutrients/nutraceuticals that are important in CRC prevention or treatment and the four metabolic pathways proposed, and the recent results of genome-wide association studies, both assisting our hypothesis. Finally, we propose a new line of investigation with larger studies, using accurate dietary biomarkers and investigating the four metabolic pathways genes simultaneously. This line of investigation will be essential to understand the full complexity of the association between nature and nurture in CRC and perhaps in other types of cancers. Only with this in-depth knowledge will it be possible to make personalised nutrition recommendations for disease prevention and management.

Framework and Strategies to Eliminate Disparities in Colorectal Cancer Screening Outcomes

Preventable differences in colorectal cancer (CRC) mortality across racial/ethnic, economic, geographic, and other groups can be eliminated by assuring equitable access and quality across the care continuum, but few interventions have been demonstrated to do so. Multicomponent strategies designed with a health equity framework may be effective. A health equity framework takes into account social determinants of health, multilevel influences (policy, community, delivery, and individual levels), screening processes, and community engagement. Effective strategies for increasing screening uptake include patient navigation and other interventions for structural barriers, reminders and clinical decision support, and data to continuously track metrics and guide targets for improvement. Community resource gaps should be addressed to assure high-quality services irrespective of racial/ethnic and socioeconomic status. One model combinespopulation-based proactive outreach screening with screening delivery at in-person or virtual points of contact, as well as community engagement. Patient- and provider-based behavioral interventions may be considered for increasing screening demand and delivery. Providing a choice of screening tests is recommended for CRC screening, and access to colonoscopy is required for completion of the CRC screening process.

Differences in Colorectal Cancer (CRC) patients who did and did not undergo screening

Abstract Background The Australian National Bowel Cancer Screening Program (NBSCP) is a free population-based screening program which aims to identify precancerous lesions and early colorectal cancer (CRC) using an immunochemical faecal occult blood test in average risk Australians. Formally commencing in 2006, NBCSP participation rate in eligible 50-74-year-old people was 42% in 2018. The barriers and facilitators of participation in the NBCSP have been explored for the general, at-risk population but not in a population of CRC patients. This is the first study to assess a population of CRC patients, post diagnosis, who would have been eligible for CRC screening to determine the barriers and facilitators to screening. Methods A cross sectional study nested within a cohort study. Data from CRC patients who participated in the 45 and Up Study; the largest cohort study in Australia and southern hemisphere, were analysed to compare those who had and had not participated in CRC screening. Logistic regression analyses were conducted using RStudio (version 3.5.2, Boston, Massachusetts, USA.). Multiple Imputation (MI), was used to handle missing values assumed to be missing at random. Results A total of 339 CRC patients were included. Patients who were female, overweight (≥25kg/m2), consumed less than the recommended five servings of vegetables per day, consumed less than or equal to fourteen standard drinks per week (compared to non-drinkers) or did not meet physical activity guidelines were significantly less likely to have participated in screening. Conclusions Our study has taken a unique approach to identifying a high-risk group by exploring factors to screening participation in CRC patients. CRC patients with less healthy lifestyles were less likely to participate in screening. In contrast to previous studies, female patients were less likely to participate in screening than males were. This was an unexpected finding and should be replicated. Key messages Not surprising that those with less healthy lifestyle practices also reflected less than ideal screening practices. Surprising that female patients participated less in screening than males. Future interventions to improve CRC screening participation rates should consider specialised messaging for average-risk females who are overweight not meeting dietary or physical activity guidelines.

Tumor Tissue MIR92a and Plasma MIRs21 and 29a as Predictive Biomarkers Associated with Clinicopathological Features and Surgical Resection in a Prospective Study on Colorectal Cancer Patients.

Cancer-related microRNAs (miRNAs) are emerging as non-invasive biomarkers for colorectal cancer (CRC). This study aimed to analyze the correlation between the levels of tissue and plasma miRNAs and clinicopathological characteristics and surgical resection. This study was a prospective study of CRC patients who underwent surgery. Forty-four sample pairs of tissue and plasma were analyzed. The miRNA levels were evaluated by RT-qPCR. The level of tumor tissue MIR92a showed a significant difference in CRC with lymph node metastasis, stage ≥ III, and high lymphatic invasion. In preoperative plasma, there were significant differences in CRC with stage ≥ III (MIR29a) and perineural invasion (MIR21). In multivariate analysis of lymphatic invasion, the levels of both preoperative plasma MIR29a and tumor tissue MIR92a showed significant differences. Furthermore, in cases with higher plasma miRNA level, the levels of plasma MIRs21 and 29a were significantly decreased after the operation. In this study, there were significant differences in miRNAs levels with respect to the sample type, clinicopathological features, and surgical resection. The levels of tumor tissue MIR92a and preoperative plasma MIR29a may have the potential as a biomarker for prognosis. The plasma MIRs21 and 29a level has the potential to be a predictive biomarker for treatment efficacy.

Better Cancer-specific Survival in Younger Patients With Stage III Colorectal Cancer: A Propensity Score Matching Study From Japan.

The purpose of this study was to explore the perioperative, short-term, and long-term prognostic differences in colorectal cancer (CRC) between young and older patients. A total of 3095 patients were divided into young (≤45 years; n=139) and older (>45 years; n=2956) groups. Then, propensity score matching was performed for patients in stage I to III according to a ratio of 1:1. The clinicopathological factors and prognosis of the two groups were studied. Young patients with CRC account for 4.49% of the total number of patients with CRC. Younger patients with CRC in stage I to III showed better cancer-specific survival (CSS). Older age was an independent risk factor for CSS prognosis. The CSS of the younger group was significantly better in stage I to III as a whole, but there was no difference in stage I and II subgroups - only in stage III. The proportion of young patients with stage III disease receiving first-line adjuvant chemotherapy was significantly higher. When young patients relapsed, they were more likely to receive second-line adjuvant chemotherapy or reoperation than older patients. Younger patients with stage III colorectal cancer had better CSS rates.

Abstract IA13: Advocate Perspective: Improving outcomes for all colorectal cancer survivors

Abstract Recent studies document striking differences in colorectal cancer (CRC) survival by race, stage at diagnosis, and state. These data demonstrate that more work is crucial to address persistent disparities in survival. Cancer survivors face many types of challenges following active treatment: physical, mental, emotional, financial, and psychosocial. CRC survivors share concerns similar to those of other cancer survivors but may also have CRC-specific concerns in survivorship due to medical interventions. Survivorship care plans (SCP) were identified as a possible way to ease the challenges experienced by cancer survivors, but results have been mixed. While some studies showed that CRC survivors appreciated a personalized SCP, many survivors needed additional detail about which providers were responsible for the varied components of their care. Importantly, diverse CRC survivors may be unaware of appropriate surveillance and follow-up recommendations. Survivors need to have the best information to support their health and well-being, and these information needs may change over time. However, there are multiple gaps in the literature, as most studies have focused on first-time CRC survivors or survivors with no additional cancers. Consequently, less is known about the experience of CRC survivors who develop new primary cancers, recurrent cancer, or metastatic cancer. Further, more information is needed about the experiences of CRC survivors who present with or are diagnosed post-treatment with additional chronic conditions. Finally, while some recent studies exist, further research could explicate the needs of survivors who have been traditionally under-represented in CRC survivorship research. Self-management is a component of achieving and maintaining health and well-being in survivorship but is not sufficient. Interventions are warranted to improve system coordination that address pervasive social determinants of health. Improving outcomes for CRC survivors will require coordinated effort at many levels, tailored to patient needs and community context. Public health organizations and their partners can play an important role in meeting the needs of diverse CRC survivors, as well as advancing the application of proven strategies in communities with the lowest CRC survival and greater deleterious outcomes post-diagnosis. Our goal remains ensuring that all men and women diagnosed with CRC experience the highest possible survival and quality of life in survivorship. Citation Format: Judith Lee Smith. Advocate Perspective: Improving outcomes for all colorectal cancer survivors [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA13.

Provider perspective: The clinical value of a novel digital medicine program in gastrointestinal oncology.

76 Background: The differences in colorectal cancer (CRC) treatment between infusion and oral chemotherapy have challenged clinical teams to maintain clinical quality and patient communications with self-administered therapies. The complexity of many regimens, such as capecitabine, creates challenges with dosing and adverse event (AE) management. The first novel Digital Medicine Program (DMP), aimed at providing support to patients and providers, was integrated into CRC treatment at Fairview Health Services and University of Minnesota Health. The DMP consists of DigiMeds (medications co-encapsulated with ingestible sensors), a wearable patch, and a mobile app to facilitate passive collection of actual medication ingestion data and biometrics over time. Methods: Beginning in September 2018, patients with CRC were offered the DMP to augment standard of care. Clinical pharmacists monitored medication adherence and biometrics in near real-time through a secure web portal. This data was used to address barriers to adherence and adjust therapy when appropriate. Qualitative data regarding provider experiences with the DMP and their interactions with patients were collected via a 5-question survey. Results: Eleven patients used the DMP (age: 66.9 ± 9.9 years (mean ± SD); patch wear: 89.9 ± 11.6%; average adherence: 91.0 ± 5.6%) for 140 ± 137 days. Providers reported that the DMP enabled data-driven decision-making by helping identify non-adherence, prompted timely dose modification for AE management, and allowed personalized care and targeted counseling. Integration of the DMP data into the Electronic Medical Record system improved utility, but providers called the DMP a “time-saver”, creating a “proactive rather than reactive” care process in “ways no other technology can do”. Providers stated patients felt more ownership of their care, and that DMP revealed newly “quantifiable positive changes” in their cancer care. Conclusions: Use of the DMP in this small cohort enabled proactive decision-making and facilitated patient-focused and efficient care. Future pragmatic, large real-world studies are underway to assess the impact of DMP on adherence, AE management, and clinical and economic outcomes.

Clinicopathologic and Racial/Ethnic Differences of Colorectal Cancer Among Adolescents and Young Adults.

OBJECTIVES:Despite overall reductions in colorectal cancer burden, incidence rates continue to rise among younger patients, and causes remain unknown. We examined differences in clinicopathologic and racial/ethnic characteristics within the adolescent and young adult (AYA) population diagnosed with colorectal cancer in the United States.METHODS:Using the National Cancer Institute's Surveillance, Epidemiology, and End Results program data, we identified individuals diagnosed with first primary colorectal cancer between ages 15 and 39 years from 2010 to 2015. Adjusted multivariable logistic regression models were used to quantify clinicopathologic and racial/ethnic differences across age at onset subgroups (15–19, 20–24, 25–29, 30–34, and 35–39 years).RESULTS:We identified 5,350 AYA patients diagnosed with colorectal cancer. Of note, 28.6% of AYA cases were diagnosed with right-sided tumors (cecum to transverse colon). The proportion of right-sided colorectal cancers differed significantly by age group at diagnosis (38.3% vs 27.3% of AYAs aged 15–19 vs 35–39 years, respectively; P trend = 0.01). Proportions of cases with mucinous adenocarcinoma and signet ring cell carcinoma histopathologic subtypes significantly increased with younger age at onset (P trends = 0.01 and 0.03, respectively). Differences in clinical stage were observed across AYA age groups, with stage II disease increasing with younger age (P trend = 0.01). The proportion of Hispanic AYAs was higher within younger patients, accounting for 21.0% of the AYA population aged 35–39 years up to 28.3% of 15–19-year-old individuals (P trend = 0.003).DISCUSSION:Within the AYA population, colorectal cancers differ by clinicopathologic and racial/ethnic characteristics. Further investigation of the clinical and biologic diversity of colorectal cancers that partially underlie age- and race-related differences in cancer susceptibility and outcomes is warranted.

Clinicopathological and molecular differences in colorectal cancer according to location

The incidence, pathogenesis, molecular pathways, and outcomes of colorectal cancer vary depending on the location of the tumor. This study aimed to compare the difference in tumor characteristics and the outcome between right-sided colon cancer and left-sided colorectal cancer (LCRC). A total of 1503 patients with colorectal cancer who underwent surgery at the Taipei Veterans General Hospital between 2000 and 2010 were enrolled in this study. Right-sided colon cancer was defined as cancers in the cecum, ascending colon, and transverse colon, while LCRC was defined as cancers in the splenic flexure colon, descending colon, sigmoid colon, and rectum. The endpoint was overall survival. The mutations were detected via polymerase chain reaction and MASS array. The prognostic value was determined using the log-rank test and the Cox regression analysis. A total of 407 and 1096 cases were classified as right-sided colon cancer and LCRC, respectively. Compared to patients with LCRC, those with right-sided colon cancer had more mucinous type cancer (7.4% vs. 3.5%), poorly differentiated tumor (11.5% vs. 3.6%), and advanced tumor-node-metastasis stage. The risk for peritoneal tumor seeding was higher in the right-sided colon cancer group (12.8% vs. 5.7%). Overall survival was better in LCRC than in right-sided colon cancer ( P=0.036). In our study, right-sided colon cancer had a more advanced tumor stage, a higher risk of peritoneal metastasis, and a poorer outcome than LCRC. Moreover, right-sided colon cancer had more gene mutations in BRAF, KRAS, SMAD4, TGF-β, PIK3CA, PTEN, AKT1, and high microsatellite instability.

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

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

Association between Cardiovascular Risk and Diabetes with Colorectal Neoplasia: A Site-Specific Analysis.

Several studies have shown site-specific differences in colorectal cancer (CRC) with respect to the risk factors. CRC was shown to be associated with cardiovascular risk (CVR) factors, but site-specific variations have not been investigated so far. This study aimed to assess the associations between the prevalence and subsite-specific differences of colorectal neoplasia and established CVR scores or known coronary artery disease (CAD) in a large asymptomatic European screening cohort (N = 2098). Participants underwent simultaneous screening colonoscopy and CVR evaluation, using the Framingham Risk Score and Heart Score. Lesions found in the colonoscopy were classified by location (proximal/distal colon or rectum). More neoplasias were found in the proximal versus the distal colon (p < 0.001). The Framingham Risk Score and Heart Score showed incremental risk for colorectal adenoma, across the tertiles in the proximal and the distal colon (p < 0.001). The prevalence of adenomas in the rectum was much lower, but also here, incremental risk could be shown for the Framingham Risk but not the Heart Risk Score tertiles. Prevalence of adenomas in the proximal colon was higher in subjects with type 2 diabetes (T2DM) (p = 0.006), but no association was found between adenomas and T2DM in the distal colon (p = 0.618) and the rectum (p = 0.071). Males had a higher CVR and more findings, in the screening colonoscopy, as compared to females, however, no site-specific differences were noted. Patients with known CAD and high CVR have an increased risk of colorectal neoplasia in both the proximal and distal colon. Patients with T2DM have a higher risk for neoplasia in the proximal colon.

Diagnostic routes and time intervals for patients with colorectal cancer in 10 international jurisdictions; findings from a cross-sectional study from the International Cancer Benchmarking Partnership (ICBP)

ObjectiveInternational differences in colorectal cancer (CRC) survival and stage at diagnosis have been reported previously. They may be linked to differences in time intervals and routes to diagnosis. The International...

Identifying factors associated with the direction and significance of microRNA tumor-normal expression differences in colorectal cancer

BackgroundmicroRNAs are small non-protein-coding RNA molecules that regulate gene expression, and have a potential epigenetic role in disease progression and survival of colorectal cancer. In terms of tumor-normal expression differences, many microRNAs exhibit evidence of being up-regulated in some subjects but down-regulated in others, or are dysregulated only for a subset of the population. We present and implement an approach to identify factors (lifestyle, tumor molecular phenotype, and survival-related) that are associated with the direction and/or significance of these microRNAs’ tumor-normal expression differences in colorectal cancer.MethodsUsing expression data for 1394 microRNAs and 1836 colorectal cancer subjects (each with both tumor and normal samples), we perform a dip test to identify microRNAs with multimodal distributions of tumor-normal expression differences. For proximal, distal, and rectal tumor sites separately, these microRNAs are tested for tumor-normal differential expression using a signed rank test, both overall and within levels of each lifestyle, tumor molecular phenotype, and survival-related factor. Appropriate adjustments are made to control the overall FDR.ResultsWe identify hundreds of microRNAs whose direction and/or significance of tumor-normal differential expression is associated with one or more lifestyle, tumor molecular phenotype, or survival-related factors.ConclusionsThe results of this study demonstrate the benefit to colorectal cancer researchers to consider multiple subject-level factors when studying dysregulation of microRNAs, whose tumor-related changes in expression can be associated with multiple factors. Our results will serve as a publicly-available resource to provide clarifying information about various factors associated with the direction and significance of tumor-normal differential expression of microRNAs in colorectal cancer.