scholarly journals Genetics in Colorectal Cancer

2021 ◽  
Vol 1 (1) ◽  
pp. 17-22
Author(s):  
Billy Peter Manawan
Keyword(s):  
Colorectal Cancer ◽  
Genetic Testing ◽  
Lynch Syndrome ◽  
Genetic Factors ◽  
Preventive Measures ◽  
Cancer Genetic ◽  
Dna Mismatch ◽  
Hamartomatous Polyposis Syndromes ◽  
Polyposis Syndromes ◽  
Apc Mutation

Colorectal cancer are the third most commonly diagnosed form of cancer globally, which about 11% of all cancer diagnoses. Obesity, together with kind of sedentary lifestyle, red meat consumption, tobacco, and alcohol consumption are considered as predisposing factors of progression of CRC.  In the development of colorectal cancer, genetic factors having a role in its incidence. The hereditary type of colorectal cancer was divided into two types is polyposis and Lynch syndrome which have each and different mechanism and genetic pattern. Lynch syndrome contributes for 3–5% of CRC cases and is caused by a germline mutation in one of four genes associated with the DNA mismatch repair (MMR) system: MLH1, MSH2, MSH6, or PMS2. In polyposis, there are some types such as Familial Adenomatous Polyposis (FAP) which mostly caused by APC mutation, MYH-associated polyposis, and the rare hamartomatous polyposis syndromes. Genetic testing and better family history documentation can enable those with a hereditary predisposition for the neoplasm to take preventive measures. Some genetic testing can be used such as Microsatellite instability (MSI), immunohistochemistry (IHC), DNA sequencing and protein truncation that used for each type of hereditary colorectal cancer.

TUMOUR PATHOLOGY PREDICTS MICROSATELLITE INSTABILITY IN A POPULATION-BASED SERIES OF COLORECTAL CANCER CASES

2008 ◽  
Vol 31 (4) ◽  
pp. 12
Author(s):  
A J Hyde ◽  
D Fontaine ◽  
R C Green ◽  
M Simms ◽  
P S Parfrey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Population Based ◽  
Pathological Features ◽  
Predictive Tool ◽  
Entire Cohort ◽  
Dna Mismatch ◽  
Bethesda Guidelines ◽  
Revised Bethesda Guidelines

Background: Lynch Syndrome is an autosomal dominant trait that accounts forapproximately 3% of all cases of colorectal cancer (CRC). It is caused by mutations in DNA mismatch repair (MMR) genes, most commonly MLH1 or MSH2. These MMR defects cause high levels of microsatellite instability (MSI-H) in the tumours. MSI testing of all CRCs to identify potential Lynch Syndrome cases is not practical, so the Bethesda Guidelines, which use clinical and pathological features, were created to identify those tumours most likely to be MSI-H^1. In 2007 Jenkins et. al. created MsPath, a tool based on the pathological features described in the rarely used 3^rd Bethesda criterion, to improve prediction of MSI-H tumours among CRC cases diagnosed before age 60 years^2. Methods: We collected a population-based cohort of 716 CRC cases diagnosed before age 75 years in Newfoundland. For each of these cases we collected family history, performed MSI analysis, and scored a number of pathological features for the purpose of evaluating the accuracy of the Bethesda Criteria and MsPath at predicting MSI-H tumours. Results: Our work validates the MsPath tool in the Newfoundland population for the same age group used to create the tool. We found it identified MSI-H cases with a sensitivity of 95% and specificity of 35% in our population of CRCcases diagnosed before age 60 years (n=290). We also tested this tool on our older population of CRCcases, diagnosed at ages 60 to 74 years (n=426). We found it to be at least as predictive in this population,with a sensitivity of 95% and a specificity of 42%. We then used our entire cohort (N=716) to compare MsPath with the other Bethesda criteria.Bethesda criteria 1, 2, 4 and 5 together predicted MSI-H cases with a sensitivity of 67% and a specificity of 51%. MsPath was better at identifying these cases, with a sensitivity of 95% and a specificity of 39%. Conclusions: We conclude that MsPath can be extended to include patients diagnosed with CRC before age 75 years. As well, we have found that MsPath is a better predictive tool than the Revised Bethesda Guidelines for identifying MSI-H cases within a population-based setting of colorectal cancer. References: 1. Umar, A. et. al. J Natl Cancer Inst 2004;96:261-8 2.Jenkins, M.A. et. al. Gastroenterology 2007;133:48-56

scholarly journals Recent advances in understanding Lynch syndrome

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2889 ◽  
Author(s):  
Sherief Shawki ◽  
Matthew F. Kalady
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Correct Diagnosis ◽  
Diagnostic Testing ◽  
Gene Mutations ◽  
The United States ◽  
Cancer Syndrome ◽  
Dna Mismatch ◽  
Recent Developments ◽  
Risk Patients

Colorectal cancer affects about 4.4% of the population and is a leading cause of cancer-related death in the United States. Approximately 10% to 20% of cases occur within a familial pattern, and Lynch syndrome is the most common hereditary colorectal cancer syndrome. Lynch syndrome is a hereditary predisposition to forming colorectal and extracolonic cancers, caused by a germline mutation in one of the DNA mismatch repair genes. Identifying at-risk patients and making a correct diagnosis are the keys to successful screening and interventions which will decrease formation of and death from cancers. Knowledge of the genetics and the natural history of Lynch syndrome has continued to be uncovered in recent years, leading to a better grasp on how these patients and their families should be managed. Recent developments include the approach to diagnostic testing, more precise definitions of the syndrome and risk stratification based on gene mutations, surgical decision-making, and chemoprevention.

scholarly journals Survey on Knowledge, Attitudes, and Training Needs of Italian Residents on Genetic Tests for Hereditary Breast and Colorectal Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Nikola Panic ◽  
Emanuele Leoncini ◽  
Paolo Di Giannantonio ◽  
Benedetto Simone ◽  
Andrea Silenzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Genetic Testing ◽  
Graduate Training ◽  
Cancer Genetic ◽  
Genetic Tests ◽  
Additional Training ◽  
Logistic Regression Models ◽  
Knowledge And Attitudes ◽  
Training Courses ◽  
Based Medicine

Objectives.The aim of the study was to assess knowledge and attitudes of medical residents working in Università Cattolica del Sacro Cuore, Rome, Italy, on genetic tests for breast and colorectal cancer.Methods.We distributed self-administered questionnaire to the residents. Logistic regression models were used to evaluate the determinants of knowledge and attitudes towards the tests.Results.Of 754 residents, 364 filled in questionnaire. Around 70% and 20% answered correctly >80% of questions on breast and colorectal cancer tests, respectively. Knowledge on tests for breast cancer was higher among residents who attended course on cancer genetic testing during graduate training (odds ratio (OR): 1.72; 95% confidence interval (CI): 1.05–2.82) and inversely associated with male gender (OR: 0.55; 95% CI: 0.35–0.87). As for colorectal cancer, residents were more knowledgeable if they attended courses on cancer genetic testing (OR: 2.08; 95% CI: 1.07–4.03) or postgraduate training courses in epidemiology and evidence-based medicine (OR: 1.95; 95% CI: 1.03–3.69). More than 70% asked for the additional training on the genetic tests for cancer during the specialization school.Conclusion.The knowledge of Italian residents on genetic tests for colorectal cancer appears to be insufficient. There is a need for additional training in this field.

Hereditary Colorectal Cancer and Polyposis Syndromes

2012 ◽  
Author(s):  
Jose G. Guillem ◽  
John B Ammori
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Prophylactic Surgery ◽  
Cancer Type ◽  
Degree Relative ◽  
Polyposis Syndrome ◽  
Clinical Criteria ◽  
Number Of Factors ◽  
Polyposis Syndromes ◽  
Peutz Jeghers Syndrome

The majority of cases of inherited colorectal cancer (CRC) are accounted for by two syndromes: Lynch syndrome and familial adenomatous polyposis (FAP). In the management of FAP, the role of prophylactic surgery is clearly defined, although the optimal procedure for an individual patient depends on a number of factors. In the management of Lynch syndrome, the indications for prophylactic procedures are emerging. The authors address the clinical evaluation, investigation findings, medical and surgical therapy, and extracolonic diseases of FAP, attenuated form of FAP (AFAP), MYH-associated polyposis, Lynch syndrome, familial colorectal cancer type X (FCCTX), hyperplastic polyposis syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. AFAP has been described that is associated with fewer adenomas and later development of CRC compared with classic FAP. The AFAP phenotype occurs in less than 10% of FAP patients. The clinical criteria for AFAP are no family members with more than 100 adenomas before the age of 30 years and (1) at least two patients with 10 to 99 adenomas at age over 30 years or (2) one patient with 10 to 99 adenomas at age over 30 years and a first-degree relative with CRC with few adenomas. Given that polyposis has a later onset and the risk of CRC is less well established in AFAP, some authors question whether prophylactic colectomy is necessary in all AFAP patients.

Evaluating the clinical utility of universal screening to identify Lynch syndrome in stage III/III colorectal cancer patients: A prospective observational study in Japan.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 41-41
Author(s):  
Yasuaki Yamamoto ◽  
Yuichiro Tsukada ◽  
Takeshi Kuwata ◽  
Motohiro Kojima ◽  
Yumie Hiraoka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Universal Screening ◽  
Clinical Utility ◽  
Braf V600e ◽  
Study Patient ◽  
Degree Relative ◽  
Western Countries ◽  
Dna Mismatch ◽  
Reflex Testing

41 Background: Universal screening for Lynch syndrome (LS) by identifying deficient DNA mismatch repair (MMR) in the tumor tissue of all new colorectal cancer (CRC) patients is widely accepted. The population prevalence of LS is approximately 3% in Western countries, whereas it is approximately 0.7% in Japan. In addition, the number of relatives diagnosed per proband is 3.6 in Western countries, whereas there are even fewer diagnoses per proband in Japan. To address the issue of LS remaining largely underdiagnosed in Japan, we prospectively evaluated the clinical utility of universal screening of LS in CRC patients. Methods: From March 2016 to August 2019, all consecutive new cases of stage II/III CRC underwent immunohistochemistry (IHC) screening for MMR using MLH1, MSH2, MSH6, and PMS2 antibodies. The patients negative for both MLH1 and PMS2 (MLH1-/PMS2-) were subjected to reflex testing for BRAF V600E mutation. Patients with both MLH1-/PMS2- and BRAF negative (cohort A, n = 14) and those with other IHC patterns (cohort B, n = 13) were referred for genetic counseling (GC) and genetic testing (GT). Furthermore, relatives of probands with confirmed LS were referred for GC/GT if they were willing. Results: Overall, 591 pts were enrolled in this study. Patient background were as follows: > 70 y/o, 35%; right-sided/left-sided colon/rectum, 24%/24%/53%; and cStage II/III, 65%/35%. Of 591 patients, 40 (6.8%) had MMR deficiency. Of 27 patients with MLH1-/PMS2-, 24 underwent BRAF reflex testing; only 10 of these patients tested positive for mutation. Of 27 patients recommended for GC, 25 were referred for GC and 22 for GT, which revealed 12 LS cases (2%, mutation genes:MLH1/PMS2/MSH2; 4/2/6). The frequency of LS diagnosis with respect to patient background was as follows: > 70/≤70 y, 1.0/2.6%; right-sided/left-sided colon/rectum, 5.8/0/1.3%; and cStage II/III, 2.6/1.0%. Interestingly, only 3 (25%) of 12 patients who underwent GC/GT in cohort A had LS compared with 9 (90%) of 10 patients in cohort B ( p= 0.004). Moreover, among 11 relatives of 5 families who were willing to undergo GC/GT, six (55%) had LS, of whom two were first-degree relatives (33%), one was a second-degree relative (50%), and three were third-degree relatives (100%). Conclusions: This study showed that universal screening of LS in CRC patients is significantly useful in Japan. Furthermore, implementing a reflex testing strategy demonstrated high adherence to guidelines and the appropriateness of our referrals for GC/GT.

scholarly journals Translational Research in Familial Colorectal Cancer Syndromes

2018 ◽  
Vol 31 (03) ◽  
pp. 161-167
Author(s):  
Molly Ford
Keyword(s):  
Colorectal Cancer ◽  
Genetic Testing ◽  
Familial Adenomatous Polyposis ◽  
Lynch Syndrome ◽  
Adenomatous Polyposis ◽  
Familial Colorectal Cancer ◽  
Inherited Cancer ◽  
Cancer Syndromes ◽  
Early Onset Colorectal Cancer ◽  
Made In

AbstractGrowing knowledge of inherited colorectal cancer syndromes has led to better surveillance and better care of this subset of patients. The most well-known entities, including Lynch syndrome and familial adenomatous polyposis, are continually being studied and with the advent of more sophisticated genetic testing, additional genetic discoveries have been made in the field of inherited cancer. This article will summarize many of the updates to both the familiar and perhaps less familiar syndromes that can lead to inherited or early-onset colorectal cancer.

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