Chemoprevention in Inherited Colorectal Cancer Syndromes
Clin Colon Rectal Surg. 2023 Jul 19;37(3):172-179. doi: 10.1055/s-0043-1770384. eCollection 2024 May.ABSTRACTCancer prevention in hereditary gastrointestinal predisposition syndromes relies primarily on intensive screening (e.g., colonoscopy) or prophylactic surgery (e.g., colectomy). The use of chemopreventive agents as an adjunct to these measures has long been studied both in the general population and in hereditary cancer patients, in whom the risk of malignancy, and therefore the potential risk reduction, is considerably greater. However, to date only few compounds have been found to be effective, safe, and tolerable ...
Source: Clinical Colorectal Cancer - April 12, 2024 Category: Cancer & Oncology Authors: Ophir Gilad Charles Muller Sonia S Kupfer Source Type: research
Evaluation of EGFR and COX pathway inhibition in human colon organoids of serrated polyposis and other hereditary cancer syndromes
This study examined effects of EGFR and COX pathway inhibition in organoid cultures derived from uninvolved colon and polyps of SPS patients. We also compared with organoids representing the hereditary gastrointestinal syndromes, Familial Adenomatous Polyposis (FAP) and Lynch syndrome (LS). Eighteen total organoid colon cultures were generated from uninvolved colon and polyps in SPS, FAP, LS, and non-syndromic screening colonoscopy patients.BRAF andKRAS mutation status was determined for each culture. Erlotinib (EGFR inhibitor) and sulindac (COX inhibitor) were applied individually and in combination. A 44-target gene cust...
Source: Familial Cancer - April 12, 2024 Category: Cancer & Oncology Source Type: research
Neoadjuvant immunotherapy in a locally advanced colon cancer patient with MSI-H and suspected Lynch syndrome: A case report
We present the case of a 46-year-old male who sought medical attention at our institution due to a history of hematochezia for two weeks, right-sided abdominal pain for one week, and loose stools. Imaging indicated duodenal involvement, and a biopsy confirmed ascending colon adenocarcinoma with MSI-H status. Given that the patient's family exhibited a history of more than three confirmed cases of colorectal cancer spanning two generations, Lynch syndrome was considered. After four cycles of PD-1 antagonist immunotherapy with carrilizumab, the patient's symptoms resolved, and physical examination revealed no abdominal tende...
Source: Zeitschrift fur Gastroenterologie - April 11, 2024 Category: Gastroenterology Authors: Xiaoyun Li Yining Xiang Yunhuan Zhen Yong Yu Source Type: research
Neoadjuvant immunotherapy in a locally advanced colon cancer patient with MSI-H and suspected Lynch syndrome: A case report
We present the case of a 46-year-old male who sought medical attention at our institution due to a history of hematochezia for two weeks, right-sided abdominal pain for one week, and loose stools. Imaging indicated duodenal involvement, and a biopsy confirmed ascending colon adenocarcinoma with MSI-H status. Given that the patient's family exhibited a history of more than three confirmed cases of colorectal cancer spanning two generations, Lynch syndrome was considered. After four cycles of PD-1 antagonist immunotherapy with carrilizumab, the patient's symptoms resolved, and physical examination revealed no abdominal tende...
Source: Zeitschrift fur Gastroenterologie - April 11, 2024 Category: Gastroenterology Authors: Xiaoyun Li Yining Xiang Yunhuan Zhen Yong Yu Source Type: research
Neoadjuvant immunotherapy in a locally advanced colon cancer patient with MSI-H and suspected Lynch syndrome: A case report
We present the case of a 46-year-old male who sought medical attention at our institution due to a history of hematochezia for two weeks, right-sided abdominal pain for one week, and loose stools. Imaging indicated duodenal involvement, and a biopsy confirmed ascending colon adenocarcinoma with MSI-H status. Given that the patient's family exhibited a history of more than three confirmed cases of colorectal cancer spanning two generations, Lynch syndrome was considered. After four cycles of PD-1 antagonist immunotherapy with carrilizumab, the patient's symptoms resolved, and physical examination revealed no abdominal tende...
Source: Zeitschrift fur Gastroenterologie - April 11, 2024 Category: Gastroenterology Authors: Xiaoyun Li Yining Xiang Yunhuan Zhen Yong Yu Source Type: research
Mitotic abnormalities precede microsatellite instability in lynch syndrome-associated colorectal tumourigenesis
This study aimed to identify precancerous functional changes in colonic mucosa that could facilitate the monitoring and prevention of cancer development in LS.METHODS: The study material comprised colon biopsy specimens (n = 71) collected during colonoscopy examinations from LS carriers (tumour-free, or diagnosed with adenoma, or diagnosed with carcinoma) and a control group, which included sporadic cases without LS or neoplasia. The majority (80%) of LS carriers had an inherited genetic MLH1 mutation. The remaining 20% included MSH2 mutation carriers (13%) and MSH6 mutation carriers (7%). The transcriptomes were first ana...
Source: Cancer Control - April 7, 2024 Category: Cancer & Oncology Authors: Marjaana Pussila Aleksi Laiho Petri T örönen Pauliina Bj örkbacka Sonja Nyk änen Kirsi Pylv änäinen Liisa Holm Jukka-Pekka Mecklin Laura Renkonen-Sinisalo Taru Lehtonen Anna Lepist ö Jere Linden Satu M äki-Nevala P äivi Peltomäki Minna Nystr öm Source Type: research
Tumor analysis of MMR genes in Lynch ‐like syndrome: Challenges associated with results interpretation
DiscussionMore biallelic somatic events were identified at VAF ≥ 5% than ≥10% (35.9% vs. 25.6%), although the rate of nonconcordant results regarding immunohistochemical pattern increased (30.8% vs. 20.5%). Interpretation difficulties question the current utility of the identification of MMR somatic hits in the diagnostic algorithm of suspected LS case s. (Source: Cancer Medicine)
Source: Cancer Medicine - April 1, 2024 Category: Cancer & Oncology Authors: Paula Rofes,
N úria Dueñas,
Jesús del Valle,
Matilde Navarro,
Judith Balmaña,
Teresa Ramón y Cajal,
Noemí Tuset,
Carmen Castillo,
Sara González,
Joan Brunet,
Gabriel Capellá,
Conxi Lázaro,
Marta Pineda Tags: RESEARCH ARTICLE Source Type: research
Challenges and opportunities for Lynch syndrome cascade testing in the United States
AbstractLynch syndrome is an underdiagnosed genetic condition that increases lifetime colorectal, endometrial, and other cancer risk. Cascade testing in relatives is recommended to increase diagnoses and enable access to cancer prevention services, yet uptake is limited due to documented multi-level barriers. Individual barriers such as feelings of fear, guilt, and anxiety and limited knowledge about Lynch syndrome as well as interpersonal barriers including complex family dynamics and language barriers limit family communication about Lynch syndrome and prevent uptake of genetic screening for relatives. Organizational and...
Source: Familial Cancer - March 28, 2024 Category: Cancer & Oncology Source Type: research
Current prospects of hereditary adrenal tumors: towards better clinical management
AbstractAdrenocortical carcinoma (ACC) and pheochromocytoma/paraganglioma (PPGL) are two rare types of adrenal gland malignancies. Regarding hereditary tumors, some patients with ACC are associated with with Li-Fraumeni syndrome (LFS), and those with PPGL with multiple endocrine neoplasia type 2. Recent studies have expanded this spectrum to include other types of hereditary tumors, such as Lynch syndrome or familial adenomatous polyposis. Individuals harboring germlineTP53 pathogenic variants that cause LFS have heterogeneous phenotypes depending on the respective variant type. As an example, R337H variant found in Brazil...
Source: Hereditary Cancer in Clinical Practice - March 26, 2024 Category: Cancer & Oncology Source Type: research
Inherited gastrointestinal cancer syndromes
Inherited gastrointestinal (GI) cancer syndromes account for 5 –10% of cancers of the GI tract. Surveillance is tailored to prevent cancer or enable its early detection. Lynch syndrome accounts for 3% of colorectal cancers (CRCs). It is caused by a germline pathogenic variant that affects one of four mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. Individual s with a variant affecting MLH1 have the highest risk of developing CRC. Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by a truncating mutation of the APC gene. (Source: Medicine)
Source: Medicine - March 26, 2024 Category: Internal Medicine Authors: Paul Collins Tags: Colorectal cancer Source Type: research
Risk of metachronous colorectal cancer after surgical resection of index rectal cancer in Lynch syndrome: a multicenter retrospective study in Japan
ConclusionThis is the first report from an East Asian country to report the risk of metachronous CRC after resection of index rectal cancer in patients with LS. Despite this study having several limitations, we cannot recommend extended resection, such as total proctocolectomy, for index rectal cancer as a standard surgical treatment in patients with LS. (Source: Surgery Today)
Source: Surgery Today - March 19, 2024 Category: Surgery Source Type: research
Immune checkpoint blockade induced sarcoid-like reaction mimicking progression of disease in a patient with microsatellite instable colorectal cancer: case report and review of the literature
CONCLUSIONS: This case highlights the propensity of SLRs to imitate progression of disease, and the importance of awareness of this adverse effect, to prompt appropriate investigation and management.PMID:38482249 | PMC:PMC10932687 | DOI:10.21037/jgo-23-435 (Source: Cancer Control)
Source: Cancer Control - March 14, 2024 Category: Cancer & Oncology Authors: Fergus Keane Elizabeth Yogiaveetil Brie Kezlarian Maria Lagratta Neil H Segal Ghassan Abou-Alfa Eileen M O'Reilly Leonard Saltz Imane El Dika Source Type: research
Cascade screening in HBOC and Lynch syndrome: guidelines and procedures in a UK centre
We present time trends (1990 –2020) of identification of index cases with germline CPG variants and numbers of subsequent cascade tests, forBRCA1,BRCA2, and the Lynch genes (MLH1,MSH2,MSH6 andPMS2). ForBRCA1/2 there was a definite increase in the proportion of index cases with ovarian cancer only and pre-symptomatic index tests both doubling from 16 to 32% and 3.2 to > 8% respectively. A mean of 1.73–1.74 additional family tests were generated for eachBRCA1/2 index case within 2 years. Overall close to one positive cascade test was generated per index case resulting in > 1000 risk reducing surgery ope...
Source: Familial Cancer - March 13, 2024 Category: Cancer & Oncology Source Type: research
On the Other Side
In this narrative medicine essay, a medical student participating in a study learns she has Lynch syndrome, setting off a cascade of emotions of dread, fear, and some hope in diagnostic plans and future breakthroughs in cancer treatment. (Source: JAMA - Journal of the American Medical Association)
Source: JAMA - Journal of the American Medical Association - March 8, 2024 Category: General Medicine Source Type: research
Adult-onset cancer predisposition syndromes in children and adolescents - to test or not to test?
Clin Cancer Res. 2024 Feb 27. doi: 10.1158/1078-0432.CCR-23-3683. Online ahead of print.ABSTRACTWith the increasing use of comprehensive germline genetic testing of children and adolescents with cancer, it has become evident that pathogenic variants (PVs) in adult-onset cancer predisposition genes (aoCPGs) underlying adult-onset cancer predisposition syndromes (aoCPS) such as Lynch syndrome or hereditary breast and ovarian cancer are enriched and reported in one to two percent of children and adolescents with cancer. However, the causal relationship between PVs in aoCPGs and childhood cancer is still under investigation. T...
Source: Clinical Cancer Research - February 27, 2024 Category: Cancer & Oncology Authors: Christian P Kratz Philip J Lupo Kristin Zelley Jaclyn Schienda Kim E Nichols Douglas R Stewart David Malkin Garrett M Brodeur Kara Maxwell Sharon E Plon Michael F Walsh Source Type: research
