Recent advances in Lynch syndrome

AbstractLynch syndrome is one of the most common hereditary cancer predisposition syndromes and is associated with increased risks of colorectal and endometrial cancer, as well as multiple other cancer types. While the mechanism of mismatch repair deficiency and microsatellite instability and its role in Lynch-associated carcinogenesis has been known for some time, there have been significant advances recently in diagnostic testing and the understanding of the molecular pathogenesis of Lynch tumors. There is also an increased awareness that the clinical phenotype and cancer risk varies by specific mismatch repair mutation, which in turn has implications on surveillance strategies for patients. Even the treatment of Lynch-associated cancers has changed with the addition of immunotherapy for advanced disease. This progress report aims to review some of the many advances in epidemiology, molecular pathogenesis, diagnosis, clinical phenotype, cancer surveillance, treatment, and chemo- and immune-prevention strategies in the Lynch syndrome field over the past 5  years.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research

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ConclusionsSporadic dMMR breast cancers are extremely rare (Davies et al. in Cancer Res 77:4755 –4762, 2017). It seems reasonable to conclude that identifying a dMMR breast cancer in a patient with known LS strongly suggests that her LS is breast cancer-predisposing. LS patients with dMMR breast cancers might therefore be considered for above-average breast cancer screening for the developme nt of additional breast cancers. Also, the FDA recently granted approval of checkpoint inhibitor therapy for all metastatic dMMR solid malignancies (Lemery et al. in N Engl J Med 377:1409–1412, 2017). MMR expression assays ...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
Abstract About 5% of colorectal cancer (CRC) cases occurred in the context of an underlying hereditary predisposition syndrome. Lynch syndrome is the main causes of hereditary CRC but is also associated with a higher risk of other cancers (such as endometrial cancer and ovarian cancer). It is the consequence of constitutional mutation in a MisMatch Repair (MMR) gene, involved in DNA repair: MLH1, MSH2, MSH6 or PMS2; or of the EPCAM gene (MSH2 promotor). If a mutation predisposing to Lynch Syndrome is identified in an individual, special monitoring should be initiated, adapted to estimated cancer risk. Clinical cri...
Source: Presse Medicale - Category: General Medicine Authors: Tags: Presse Med Source Type: research
Publication date: Available online 21 August 2019Source: Journal of Visceral SurgeryAuthor(s): B. Menahem, A. Alves, J.M. Regimbeau, C. SabbaghSummaryNearly 5% of colorectal cancers are related to constitutional genetic abnormalities. In Lynch Syndrome (LS), the abnormality is a mutation of the deoxyribonucleic acid (DNA) repair system. The goal of this update is to update indications and surgical strategies for patients with LS. Different spectra of disease are associated with LS. The narrow spectrum includes cancers with a high relative risk: colorectal cancer (CRC), endometrial cancer, urinary tract cancers and small in...
Source: Journal of Visceral Surgery - Category: Surgery Source Type: research
ConclusionsThe data suggest that feeling efficacious about managing one ’s Lynch syndrome and screening is related to positive interactions and communication with one’s family physician. While this is encouraging, future research should examine educating both family physicians and patients about current guidelines for Lynch syndrome gynecological screening recommend ations.
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research
Lynch Syndrome (LS) is a dominantly inherited condition with incomplete penetrance, characterized by high predisposition to colorectal cancer (CRC), endometrial and ovarian cancers, as well as to other tumors. LS is associated with constitutive DNA mismatch repair (MMR) gene defects, and carriers of the same pathogenic variants can show great phenotypic heterogeneity in terms of cancer spectrum. In the last years, human gut microbiota got a foothold among risk factors responsible for the onset and evolution of sporadic CRC, but its possible involvement in the modulation of LS patients’ phenotype still needs to be inv...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
ConclusionConcordance of opinion among GCs for the management of patients with negative genetic test results exists when FDRs are affected. However, when affected relatives are more distant, GCs disagreed on screening recommendations. These data suggest a need for guidelines for patients with a family history of cancer and a negative genetic test.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: CLINICAL REPORT Source Type: research
ConclusionsThis case highlights the importance of genetic testing with rare malignancies because the full scope of phenotypic sequelae for known hereditary syndromes has not been mapped.
Source: Journal of Medical Case Reports - Category: General Medicine Source Type: research
Lynch Syndrome (LS) entails a defective DNA mismatch repair system, which is the post-replicative proofreading and editing system, ensuring our genome's integrity. LS predisposes to several cancers, most commonly colorectal and endometrial cancers. LS occurs in approximately 1 in 250 –1,000 people.LS is associated with urological malignancies with upper tract urothelial carcinoma the most common, although still clinically underestimated. Other urologic malignancies possibly associated with LS include bladder, prostate, testis, and renal cell carcinoma.
Source: Urology - Category: Urology & Nephrology Authors: Source Type: research
AbstractLynch syndrome is a cancer-predisposing syndrome inherited in an autosomal-dominant manner, wherein colon cancer and endometrial cancer develop frequently in the family, it results from a loss-of-function mutation in one of four different genes (MLH1,MSH2,MSH6, andPMS2) encoding mismatch repair proteins. Being located immediately upstream of theMSH2 gene,EPCAM abnormalities can affectMSH2 and cause Lynch syndrome. Mismatch repair proteins are involved in repairing of incorrect pairing (point mutations and deletion/insertion of simple repetitive sequences, so-called microsatellites) that can arise during DNA replica...
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research
AbstractLifestyle factors related to energy balance, such as excess body weight, poor diet, and physical inactivity, are associated with risk of sporadic endometrial cancer (EC) and colorectal cancer (CRC). There are limited data on energy balance-related lifestyle factors and EC or CRC risk among individuals with lynch syndrome, who are at extraordinarily higher risk of developing EC or CRC. We conducted a systematic review of evidence related to weight status, weight change, dietary habits, and physical activity on EC and CRC risk among individuals with lynch syndrome. Findings are reported narratively. We searched Medli...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
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