The clinical and molecular characteristics of patients with personal history of colorectal cancer evaluated by cancer genetics counseling services.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 46-46
Author(s):  
Veena Krishnan ◽  
Cassandra Gurganus ◽  
Delmer Alfredo Montoya Motino ◽  
Gideon T Dosunmu ◽  
Sana Ozair ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Cancer Genetics ◽  
Germline Mutations ◽  
Personal History ◽  
Molecular Characteristics ◽  
Counseling Services ◽  
Polyposis Syndrome ◽  
History Of ◽  
Germline Testing

46 Background: Genetic susceptibility to colorectal cancer (CRC) include well-defined hereditary syndromes such as Lynch Syndrome, Familial Adenomatous Polyposis syndrome (FAP), MUTYH-Associated Polyposis syndrome (MAP) and other less common syndromes. National Comprehensive Cancer Network (NCCN) guidelines recommend that individuals meeting certain criteria have detailed risk assessment and potential genetic testing. Here, we describe the clinical and molecular characteristics of patients with personal history of CRC evaluated by cancer genetics counseling services. Methods: This is an IRB-approved retrospective chart-review study. Between 2016 and 2020, 1011 unique genetic counseling visits were conducted. Germline testing was recommended by a certified genetic counselor if medically necessary. All patients with a personal history of CRC were identified (N = 52) and their clinical and molecular characteristics were summarized. Results: The median age is 50 years-old (29-82). Thirty-five (67%) patients were females. Caucasians, African Americans and other ethnic backgrounds represented 75%, 19% and 6% respectively. The primary tumor location was in the right colon, left colon and rectum in 29%, 37% and 27% of our cohort respectively. In 7%, the primary location of the tumor was not available. In our cohort, 11 out of 52 (21%) patients had a pathogenic germline mutation and 9 patients (17%) had a germline variant of unknown significance (VUS). Among patients with pathogenic germline mutations (N = 11), 4 patients had MSH2 mutations (MSH2 c.1759+1G > A, MSH2 c. 1687dupT, MSH2 c.1861C > T and MSH2 c.811_814delTCTG), 1 patient had a MSH6 mutation (MSH6 c.1012A > T), 1 patient had a PMS2 mutation (PMS2 c.2182_2184delACTinsG), 3 patients had CHEK2 mutations (CHEK2 c.1100delC and CHEK2 c.470T > C (p.I157T)), 2 patients had MUTYH mutations (MUTYH c.1187G > A and MUTYH c.536A > G) and 1 patient had a BRCA2 mutation (BRCA2 c.2808_2811delACAA). One patient had a CHEK2 and a MUTYH mutation. The VUS mutations in our cohort were POLE c.1645T > C, POLE c.5480C > T, c.2999G > A, MLH1 c.1628A > G, CTNNA1 c.503G > A, MSH2 c.128A > G, NBN c.16C > T, ATM c.6537T > G and AXIN2, BRCA1, NTHL1 mutations. Conclusions: In our cohort of patients with personal history of CRC, the majority of patients (62%) had negative germline testing. An underlying pathogenic germline mutation and VUS were identified in 21% and 17% of the patients respectively. Lynch Syndrome was the most commonly diagnosed hereditary CRC syndrome with 6 out of 11 patients found to have MMR germline mutations. Other pathogenic mutations were identified in the CHEK2, MUTYH and BRCA2 genes.

Germline testing of patients with personal history of colorectal polyposis by cancer genetics counseling services.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 47-47
Author(s):  
Gideon T Dosunmu ◽  
Cassandra Gurganus ◽  
Veena Krishnan ◽  
Delmer Alfredo Montoya Motino ◽  
Sana Ozair ◽  
...  
Keyword(s):  
Cancer Genetics ◽  
Germline Mutations ◽  
Colorectal Polyps ◽  
Personal History ◽  
Counseling Services ◽  
Polyposis Syndrome ◽  
Hamartomatous Polyps ◽  
Colorectal Polyposis ◽  
History Of ◽  
Germline Testing

47 Background: National Comprehensive Cancer Network (NCCN) guidelines recommend that individuals with >10 adenomatous polyps, ≥2 hamartomatous polyps, or ≥5 serrated polyps proximal to the sigmoid colon have detailed risk assessment and potential genetic testing to rule out polyposis syndrome. Here, we describe germline testing of patients with a personal history of colorectal polyposis by Cancer Genetics Counseling Services. Methods: This is an IRB-approved retrospective chart-review study. Between 2016 and 2020, 1011 unique genetic counseling visits were conducted. Germline testing was recommended by a certified genetic counselor if medically necessary. All patients with a personal history of colorectal polyposis were identified (N=20) and their germline testing results were summarized. Results: The reasons for referral to the Cancer Genetics Counseling Services were personal history of >10 adenomatous polyps (N=13), personal and family history of colorectal polyposis (N=3), personal history of juvenile colorectal polyps (N=3) or personal history of ≥2 hamartomatous polyps (N=1). The median age is 58 years-old (1-84). Ten (50%) patients were females. Caucasians, African Americans and other ethnic backgrounds represented 80%, 10% and 10% respectively. In our cohort, 6 out of 20 (30%) patients had a pathogenic germline mutation, 5 (25%) patients had variant of unknown significance (VUS) and 9 (45%) patients had negative testing. Among patients with pathogenic germline mutations, 3 patients had a pathogenic APC mutation (APC c.1659G>A, APC c.2802C>A and APC c.1643dupT) and were diagnosed with Familial Adenomatous Polyposis (FAP). One patient had 2 pathogenic MUTYH mutations (MUTYH c.536A>G and MUTYH c.1187G>A) and was diagnosed with One patient had a pathogenic PTEN c.634+5G>A mutation and was diagnosed with PTEN Hamartoma Tumor Syndrome. Among the 3 patients with a personal history of juvenile colorectal polyps, one patient had a CHEK2 c.190G>A mutation while the other two had negative genetic test results. The VUS mutations in our cohort were MRE11A c.826C>T, BLM c.3478T>C, BRCA2 c.2519T>C, CHEK2 p.V395L and CTNNA1 c.392dupT. Conclusions: In our cohort of patients with personal history of colorectal polyposis, the majority of patients (45%) had negative germline testing. An underlying pathogenic germline mutation and VUS were identified in 30% and 25% of the patients, respectively. FAP Syndrome was the most commonly diagnosed hereditary polyposis syndrome with 3 patients found to have APC germline mutations. Other pathogenic mutations were identified in the MUTYH, PTEN and CHEK2 genes. Patients with MUTYH and PTEN mutations were diagnosed with MAP and PTEN Hamartoma Tumor Syndromes respectively.

scholarly journals Cumulative risks of colorectal cancer in Han Chinese patients with Lynch syndrome in Taiwan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abram Bunya Kamiza ◽  
Wen-Chang Wang ◽  
Jeng-Fu You ◽  
Reiping Tang ◽  
Huei-Tzu Chien ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Cumulative Risk ◽  
Germline Mutations ◽  
Han Chinese ◽  
Chinese Patients ◽  
Mutation Carriers ◽  
Amsterdam Criteria ◽  
Cumulative Risks ◽  
Age And Sex

AbstractPatients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%–89.9%) and 76.7% (95% CI = 37.2%–99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%–57.7%) and 49.3% (95% CI = 21.9%–84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.

scholarly journals Clinical, Pathological and Molecular Characteristics of Chilean Patients with Early-, Intermediate- and Late-Onset Colorectal Cancer

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 631
Author(s):  
Karin Alvarez ◽  
Alessandra Cassana ◽  
Marjorie De La Fuente ◽  
Tamara Canales ◽  
Mario Abedrapo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Age Of Onset ◽  
Late Onset ◽  
Molecular Characteristics ◽  
Family History Of Cancer ◽  
Molecular Features ◽  
Age Of Diagnosis ◽  
History Of ◽  
History Of Cancer

Colorectal cancer (CRC) is the second most frequent neoplasm in Chile and its mortality rate is rising in all ages. However, studies characterizing CRC according to the age of onset are still lacking. This study aimed to identify clinical, pathological, and molecular features of CRC in Chilean patients according to the age of diagnosis: early- (≤50 years; EOCRC), intermediate- (51–69 years; IOCRC), and late-onset (≥70 years; LOCRC). The study included 426 CRC patients from Clinica Las Condes, between 2007 and 2019. A chi-square test was applied to explore associations between age of onset and clinicopathological characteristics. Body Mass Index (BMI) differences according to age of diagnosis was evaluated through t-test. Overall (OS) and cancer-specific survival (CSS) were estimated by the Kaplan–Meier method. We found significant differences between the age of onset, and gender, BMI, family history of cancer, TNM Classification of Malignant Tumors stage, OS, and CSS. EOCRC category was characterized by a family history of cancer, left-sided tumors with a more advanced stage of the disease but better survival at 10 years, and lower microsatellite instability (MSI), with predominant germline mutations. IOCRC has shown clinical similarities with the EOCRC and molecular similarities to the LOCRC, which agrees with other reports.

Hereditary Colorectal Cancer and Polyposis Syndromes

2021 ◽  
Author(s):  
Jose G. Guillem ◽  
John B Ammori
Keyword(s):  
Colorectal Cancer ◽  
Familial Adenomatous Polyposis ◽  
Lynch Syndrome ◽  
Juvenile Polyposis ◽  
Prophylactic Surgery ◽  
Cancer Type ◽  
Adenomatous Polyposis ◽  
Juvenile Polyposis Syndrome ◽  
Polyposis Syndrome ◽  
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. This review contains 26 tables and 173 references Keywords: Colorectal cancer, Lynch syndrome, hyperplastic polyp, Peutz-Jeghers syndrome, juvenile polyposis syndrome, familial adenomatous polyposis

scholarly journals Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG)

Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 411-444 ◽  
Author(s):  
Kevin J Monahan ◽  
Nicola Bradshaw ◽  
Sunil Dolwani ◽  
Bianca Desouza ◽  
Malcolm G Dunlop ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Great Britain ◽  
Family History ◽  
Cancer Genetics ◽  
Genetic Diagnosis ◽  
Lifetime Risk ◽  
British Society ◽  
Screening And Surveillance ◽  
History Of ◽  
The Uk

Heritable factors account for approximately 35% of colorectal cancer (CRC) risk, and almost 30% of the population in the UK have a family history of CRC. The quantification of an individual’s lifetime risk of gastrointestinal cancer may incorporate clinical and molecular data, and depends on accurate phenotypic assessment and genetic diagnosis. In turn this may facilitate targeted risk-reducing interventions, including endoscopic surveillance, preventative surgery and chemoprophylaxis, which provide opportunities for cancer prevention. This guideline is an update from the 2010 British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland (BSG/ACPGBI) guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC. On this occasion we invited the UK Cancer Genetics Group (UKCGG), a subgroup within the British Society of Genetic Medicine (BSGM), as a partner to BSG and ACPGBI in the multidisciplinary guideline development process. We also invited external review through the Delphi process by members of the public as well as the steering committees of the European Hereditary Tumour Group (EHTG) and the European Society of Gastrointestinal Endoscopy (ESGE). A systematic review of 10 189 publications was undertaken to develop 67 evidence and expert opinion-based recommendations for the management of hereditary CRC risk. Ten research recommendations are also prioritised to inform clinical management of people at hereditary CRC risk.

Risk of colonic adenoma in patients with non–colorectal cancers.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13070-e13070
Author(s):  
Hamzah Abu-Sbeih ◽  
Faisal Ali ◽  
Wei Qiao ◽  
Phillip Lum ◽  
Mehnaz Shafi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
The United States ◽  
Personal History ◽  
Control Group ◽  
Colonic Adenoma ◽  
Crc Screening ◽  
Adenoma Detection ◽  
Increased Risk ◽  
History Of

e13070 Background: In the last two decades, the incidence of colorectal cancer (CRC) has decreased dramatically after the implementation of CRC screening in the United States. Several risk factors for colonic adenoma (CA), the main precursor for CRC, have been found. Whether personal history of non-colorectal cancer (NCRC) is a risk factor for CA has not been studied. Here, we assess the risk of CA in patients with NCRCs. Methods: We conducted a retrospective study of cancer patients who underwent colonoscopy after cancer diagnosis between 2009 and 2018. We included patients without history of NCRC as a control group. Multivariate logistic regression was used to assess independent risk factors for CA (Table 1). Results: Total of 9408 patients with NCRC were included; CA was detected in 4503 (48%). Histology revealed tubulovillous features in 611 (14%) patients and villous in 51 (1%). High grade dysplasia was detected in 1,317 (29%) patients and adenocarcinoma in 388 (9%). The rate of adenocarcinoma was the highest in patients with multiple myeloma (14%). Adenoma detection rate (ADR) was 30% in patients younger than 40 years ( n= 1621), 32% in patients between 40 and 50 years ( n= 812), 47% in patients between 50 and 60 years ( n= 2892), and 55% in patients older than 60 years ( n= 4493). Multivariate analysis revealed an increased risk of CA with old age, male sex, family history of CRC, and high body mass index ( P< 0.05). The median time from NCRC diagnosis to CA detection was 3 years (IQR 1-8). Conclusions: ADR in patients with a personal history of NCRC is higher than the ADR of patients without NCRC. CRC screening should be performed after the diagnosis of NCRC is made, even if it was before the standard threshold of CRC screening age of 50 years.[Table: see text]

Mismatch Repair Genes and EPCAM germline mutations in patients with gastric or colorectal cancer with suspected of Lynch syndrome.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e13623-e13623 ◽  
Author(s):  
Nora Manoukian Forones ◽  
Fernanda Tereza Lima ◽  
Renan Paulo Martin ◽  
Leonardo Martins ◽  
Patricia Valera Lima Teixeira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Germline Mutations ◽  
Mismatch Repair Genes ◽  
Repair Genes

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.

Polyposis Syndromes

2020 ◽  
Author(s):  
Katherine A Kelley ◽  
Daniel O Herzig
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Future Research ◽  
Molecular Characteristics ◽  
Inherited Disorders ◽  
Polyposis Syndrome ◽  
Screening Guidelines ◽  
Increased Risk ◽  
Polyposis Syndromes

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer death in men and women. Although about one third of cancers arise in patients with a family history of CRC, only 5% arise in the setting of mendelian-inherited disorders. Patients without a family history but with a significant polyp burden (> 20 polyps) should be considered to have polyposis syndrome. The field of polyposis syndromes continues to advance, based on new genetic discoveries that define the genetic etiologies of polyposis syndromes. When considered in relation to an individual’s phenotype, these discoveries help guide screening and treatment based on the cancer risk created by specific mutations. Patients with polyposis syndromes carry an increased risk of CRC and some other extracolonic cancers. Future research will provide additional insight into the cause of polyposis syndromes without a currently detectable gene defect and will improve early identification and cancer prevention in affected individuals. Identification of additional molecular characteristics may lead to a more personalized approach to treatment for these individuals. This review contains 7 figures, 11 tables and 52 references. Key words: attenuated familial polyposis, colorectal cancer risk, familial adenomatous polyposis, hamartomatous polyposis syndrome, juvenile polyposis syndrome, MUTYH-associated polyposis, Peutz-Jeghers syndrome, polyposis syndromes, screening guidelines, serrated polyposis syndrome  

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