A large-scale and robust dynamic MRM study of colorectal cancer biomarkers

2018 ◽  
Vol 187 ◽  
pp. 80-92 ◽  
Author(s):  
Jia You ◽  
Athit Kao ◽  
Roslyn Dillon ◽  
Lisa J. Croner ◽  
Ryan Benz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Large Scale ◽  
Cancer Biomarkers

scholarly journals Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis

2021 ◽  
Author(s):  
Richard Culliford ◽  
Alex J. Cornish ◽  
Philip J. Law ◽  
Susan M. Farrington ◽  
Kimmo Palin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Large Scale ◽  
Causal Effect ◽  
Gallstone Disease ◽  
Epidemiological Studies ◽  
Mendelian Randomisation ◽  
Linear Relationships ◽  
Potential Risk Factors ◽  
The Relationship ◽  
Circulating Levels

Abstract Background Epidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we examine the relationship between these potential risk factors and CRC using Mendelian randomisation (MR). Methods We used two-sample MR to examine the relationship between genetic liability to gallstone disease and circulating levels of bilirubin with CRC in 26,397 patients and 41,481 controls. We calculated the odds ratio per genetically predicted SD unit increase in log bilirubin levels (ORSD) for CRC and tested for a non-zero causal effect of gallstones on CRC. Sensitivity analysis was applied to identify violations of estimator assumptions. Results No association between either gallstone disease (P value = 0.60) or circulating levels of bilirubin (ORSD = 1.00, 95% confidence interval (CI) = 0.96–1.03, P value = 0.90) with CRC was shown. Conclusions Despite the large scale of this study, we found no evidence for a causal relationship between either circulating levels of bilirubin or gallstone disease with risk of developing CRC. While the magnitude of effect suggested by some observational studies can confidently be excluded, we cannot exclude the possibility of smaller effect sizes and non-linear relationships.

scholarly journals Use of Antiplatelet Agents Decreases the Positive Predictive Value of Fecal Immunochemical Tests for Colorectal Cancer but Does Not Affect Their Sensitivity

2021 ◽  
Vol 11 (6) ◽  
pp. 497
Author(s):  
Yoonsuk Jung ◽  
Eui Im ◽  
Jinhee Lee ◽  
Hyeah Lee ◽  
Changmo Moon
Keyword(s):  
Colorectal Cancer ◽  
Large Scale ◽  
Screening Program ◽  
Antiplatelet Agents ◽  
Population Based ◽  
Small Sample ◽  
Antithrombotic Agents ◽  
Predictive Values ◽  
Prescription Rates ◽  
Small Sample Sizes

Previous studies have evaluated the effects of antithrombotic agents on the performance of fecal immunochemical tests (FITs) for the detection of colorectal cancer (CRC), but the results were inconsistent and based on small sample sizes. We studied this topic using a large-scale population-based database. Using the Korean National Cancer Screening Program Database, we compared the performance of FITs for CRC detection between users and non-users of antiplatelet agents and warfarin. Non-users were matched according to age and sex. Among 5,426,469 eligible participants, 768,733 used antiplatelet agents (mono/dual/triple therapy, n = 701,683/63,211/3839), and 19,569 used warfarin, while 4,638,167 were non-users. Among antiplatelet agents, aspirin, clopidogrel, and cilostazol ranked first, second, and third, respectively, in terms of prescription rates. Users of antiplatelet agents (3.62% vs. 4.45%; relative risk (RR): 0.83; 95% confidence interval (CI): 0.78–0.88), aspirin (3.66% vs. 4.13%; RR: 0.90; 95% CI: 0.83–0.97), and clopidogrel (3.48% vs. 4.88%; RR: 0.72; 95% CI: 0.61–0.86) had lower positive predictive values (PPVs) for CRC detection than non-users. However, there were no significant differences in PPV between cilostazol vs. non-users and warfarin users vs. non-users. For PPV, the RR (users vs. non-users) for antiplatelet monotherapy was 0.86, while the RRs for dual and triple antiplatelet therapies (excluding cilostazol) were 0.67 and 0.22, respectively. For all antithrombotic agents, the sensitivity for CRC detection was not different between users and non-users. Use of antiplatelet agents, except cilostazol, may increase the false positives without improving the sensitivity of FITs for CRC detection.

Progressive alteration of DNA methylation of Alu, MGMT, MINT2, and TFPI2 genes in colonic mucosa during colorectal cancer development

2021 ◽  
pp. 1-6
Author(s):  
Ben Kang ◽  
Hyun Seok Lee ◽  
Seong Woo Jeon ◽  
Soo Yeun Park ◽  
Gyu Seog Choi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Healthy Subjects ◽  
Large Scale ◽  
Methylation Status ◽  
Clinical Information ◽  
Field Cancerization ◽  
Aberrant Methylation ◽  
Clinical Value ◽  
Mortality And Morbidity

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. It is characterized by different pathways of carcinogenesis and is a heterogeneous disease with diverse molecular landscapes that reflect histopathological and clinical information. Changes in the DNA methylation status of colon epithelial cells have been identified as critical components in CRC development and appear to be emerging biomarkers for the early detection and prognosis of CRC. OBJECTIVE: To explore the underlying disease mechanisms and identify more effective biomarkers of CRC. METHODS: We compared the levels and frequencies of DNA methylation in 11 genes (Alu, APC, DAPK, MGMT, MLH1, MINT1, MINT2, MINT3, p16, RGS6, and TFPI2) in colorectal cancer and its precursor adenomatous polyp with normal tissue of healthy subjects using pyrosequencing and then evaluated the clinical value of these genes. RESULTS: Aberrant methylation of Alu, MGMT, MINT2, and TFPI2 genes was progressively accumulated during the normal-adenoma-carcinoma progression. Additionally, CGI methylation occurred either as an adenoma-associated event for APC, MLH1, MINT1, MINT31, p16, and RGS6 or a tumor-associated event for DAPK. Moreover, relatively high levels and frequencies of DAPK, MGMT, and TFPI2 methylation were detected in the peritumoral nonmalignant mucosa of cancer patients in a field-cancerization manner, as compared to normal mucosa from healthy subjects. CONCLUSION: This study identified several biomarkers associated with the initiation and progression of CRC. As novel findings, they may have important clinical implications for CRC diagnostic and prognostic applications. Further large-scale studies are needed to confirm these findings.

scholarly journals High prevalence of TP53 loss and whole-genome doubling in early-onset colorectal cancer

2021 ◽  
Author(s):  
Jeong Eun Kim ◽  
Jaeyong Choi ◽  
Chang-Ohk Sung ◽  
Yong Sang Hong ◽  
Sun Young Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Large Scale ◽  
Late Onset ◽  
Age Groups ◽  
The Cancer Genome Atlas ◽  
Whole Genome ◽  
Genome Doubling ◽  
Whole Genome Doubling ◽  
Early Onset Colorectal Cancer

AbstractThe global incidence of early-onset colorectal cancer (EO-CRC) is rapidly rising. However, the reason for this rise in incidence as well as the genomic characteristics of EO-CRC remain largely unknown. We performed whole-exome sequencing in 47 cases of EO-CRC and targeted deep sequencing in 833 cases of CRC. Mutational profiles of EO-CRC were compared with previously published large-scale studies. EO-CRC and The Cancer Genome Atlas (TCGA) data were further investigated according to copy number profiles and mutation timing. We classified colorectal cancer into three subgroups: the hypermutated group consisted of mutations in POLE and mismatch repair genes; the whole-genome doubling group had early functional loss of TP53 that led to whole-genome doubling and focal oncogene amplification; the genome-stable group had mutations in APC and KRAS, similar to conventional colon cancer. Among non-hypermutated samples, whole-genome doubling was more prevalent in early-onset than in late-onset disease (54% vs 38%, Fisher’s exact P = 0.04). More than half of non-hypermutated EO-CRC cases involved early TP53 mutation and whole-genome doubling, which led to notable differences in mutation frequencies between age groups. Alternative carcinogenesis involving genomic instability via loss of TP53 may be related to the rise in EO-CRC.

scholarly journals Colorectal Cancer Biomarkers in the Era of Personalized Medicine

2019 ◽  
Vol 9 (1) ◽  
pp. 3 ◽  
Author(s):  
Jai Patel ◽  
Mei Fong ◽  
Megan Jagosky
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Therapy Response ◽  
Dose Intensity ◽  
Cancer Biomarkers ◽  
Clinical Implications ◽  
Test Results ◽  
First Line ◽  
Genomic Markers ◽  
Generation Sequencing

The 5-year survival probability for patients with metastatic colorectal cancer has not drastically changed over the last several years, nor has the backbone chemotherapy in first-line disease. Nevertheless, newer targeted therapies and immunotherapies have been approved primarily in the refractory setting, which appears to benefit a small proportion of patients. Until recently, rat sarcoma (RAS) mutations remained the only genomic biomarker to assist with therapy selection in metastatic colorectal cancer. Next generation sequencing has unveiled many more potentially powerful predictive genomic markers of therapy response. Importantly, there are also clinical and physiologic predictive or prognostic biomarkers, such as tumor sidedness. Variations in germline pharmacogenomic biomarkers have demonstrated usefulness in determining response or risk of toxicity, which can be critical in defining dose intensity. This review outlines such biomarkers and summarizes their clinical implications on the treatment of colorectal cancer. It is critical that clinicians understand which biomarkers are clinically validated for use in practice and how to act on such test results.

scholarly journals Adjuvant treatment of colorectal cancer

2002 ◽  
Vol 49 (2) ◽  
pp. 15-18
Author(s):  
J.A. Wils
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Treatment ◽  
Large Scale ◽  
New Drugs ◽  
Morbidity And Mortality ◽  
The Past ◽  
The Future ◽  
The Usa

Colorectal cancer is a leading cause of morbidity and mortality, with approximately 300,000 new cases and 200,000 related deaths in Europe and the USA each year. Adjuvant treatment of colorectal cancer is now widely accepted and can reduce mortality with approximately 10%. This can be considered as one of the major achievements in oncology from the past decade. Current results will be discussed and strategies for the future will be outlined, including on-going or planned large-scale trials with new drugs and approaches.

scholarly journals Colorectal Cancer Prevalence and Survival in Castilla La Mancha (Spain). A Pilot Study

2021 ◽  
Author(s):  
Laura Valiente González ◽  
Ricardo de Miguel Ibáñez ◽  
Francisco Escribano Sotos
Keyword(s):  
Colorectal Cancer ◽  
Pilot Study ◽  
Large Scale ◽  
Cox Regression ◽  
Epidemiological Studies ◽  
Cancer Type ◽  
Tumour Stage ◽  
Cancer Prevalence ◽  
La Mancha

Abstract Background: Colorectal cancer is the most commonly diagnosed cancer type and the second cause of cancer death in Spain. The primary risk factor for colorectal cancer is age, with 90% of all diagnosed patients aged over 50 years. Prognosis mainly depends on tumour stage. Aim: Conduct a pilot Colorectal Cancer prevalence and survival study in Cuenca (Spain) since there are almost no studies based on small populations. This is the first pilot study about survival in screening of colorectal cancer carried out in hospitals in Castilla La Mancha. Methods and Results: Retrospective descriptive cohort study was performed to include patients with colorectal cancer diagnosed by colonoscopy between May 2015 and April 2016, and who were followed up for 48 months. The study considered sociodemographic and clinical data of the patients. Survival curves were estimated using the Kaplan-Meier method. The proportional hazard rate associated with age, gender, stage and presence of metastasis was calculated using the Cox regression method. 57 patients were included in the study. The mean follow-up was 45.5 months. Ten patients died during the study, in seven cases the cause was colorectal cancer. The percentage of patients alive at 48-month follow-up were 82.4%. Conclusion: Colon cancer is a high-prevalence pathology, with adenocarcinoma being the most common histology. The results seem to indicate that it affects men more frequently, mortality rises with tumour stage at diagnosis and declines with use of chemotherapy. We present a pilot study that could justify large-scale epidemiological studies for the regional surveillance and evolution of colorectal cancer in Spain.

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