The Potential for Reducing Lynch Syndrome Cancer Risk with Nutritional Nrf2 Activators.

The Potential for Reducing Lynch Syndrome Cancer Risk with Nutritional Nrf2 Activators. Nutr Cancer. 2020 Apr 11;:1-16 Authors: Aussem A, Ludwig K Abstract Lynch syndrome (LS), is an autosomal dominant disorder predisposing patients to multiple cancers, predominantly colorectal (CRC) and endometrial, and is implicated in 2-4% of all CRC cases. LS is characterized by mutations of four mismatch repair (MMR) genes which code for proteins responsible for recognizing and repairing DNA lesions occurring through multiple mechanisms including oxidative stress (OS). Increased OS can cause DNA mutations and is considered carcinogenic. Due to reduced MMR activity, LS patients have an increased risk of cancer as a result of a decreased ability to recognize and repair DNA lesions caused by OS. Due to its carcinogenic properties, reducing the level of OS may reduce the risk of cancer. Nutritional Nrf2 activators have been shown to reduce the risk of carcinogenesis in the general population through activation of the endogenous antioxidant system. Common nutritional Nrf2 activators include sulforaphane, curcumin, DATS, quercetin, resveratrol, and EGCG. Since LS patients are more susceptible to carcinogenesis caused by OS, it is hypothesized that nutritional Nrf2 activators may have the potential to reduce the risk of cancer in those with LS by modulating OS and inflammation. The purpose of this paper is to review the available evidence in support of this statement. ...
Source: Nutrition and Cancer - Category: Cancer & Oncology Authors: Tags: Nutr Cancer Source Type: research

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c Samuel Aguiar Junior Edenir Inez Palmero José Cláudio Casali-da-Rocha Dirce Maria Carraro Giovana Tardin Torrezan Lynch syndrome (LS) is a hereditary cancer-predisposing syndrome associated most frequently with epithelial tumors, particularly colorectal (CRC) and endometrial carcinomas (EC). The aim of this study was to investigate the relationship between sarcomas and LS by performing clinical and molecular characterization of patients presenting co-occurrence of sarcomas and tumors from the LS spectrum. We identified 27 patients diagnosed with CRC, EC, and other LS-associated tumors who had ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Lynch syndrome (LS) is an autosomal dominant disease caused by a germline mutation in DNA mismatch repair genes which increases the risk of several cancers such as endometrial and colorectal cancers. However, there are only a few reports of peritoneal malignancies in patients with LS. Herein, we report the first case of a primary peritoneal low-grade serous carcinoma in a woman with LS and provide a literature review of peritoneal malignancies in patients with LS. The patient was a 72-yr-old gravid 2 para 2 Japanese woman with a germline mutation in MLH1. She had a history of colon cancer and endometrial cancer and was tre...
Source: International Journal of Gynecological Pathology - Category: Pathology Tags: PATHOLOGY OF THE UPPER TRACT: CASE REPORTS Source Type: research
ConclusionThese results indicate that there is scope to further increase provision of advice at FCCs to ensure that all carriers receive recommendations about evidence-based risk management. A multi-pronged behaviour change and implementation science approach tailored to specific barriers is likely to be needed to achieve optimal clinician behaviours and outcomes for carriers.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
In conclusion, somatic mutational signatures suggest that conventional MMR status of tumor tissues is likely to underestimate the significance of the predisposing MMR defects as contributors to breast tumorigenesis in LS. PMID: 32292574 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Mismatch repair deficiency (MMRD) is involved in the initiation of both hereditary and sporadic tumors. MMRD has been extensively studied in colorectal cancer and endometrial cancer, but not so in other tumors, such as ovarian carcinoma. We have determined the expression of mismatch repair proteins in a large cohort of 502 early-stage epithelial ovarian carcinoma entailing all the 5 main subtypes: high-grade serous carcinoma, endometrioid ovarian carcinoma (EOC), clear cell carcinoma (CCC), mucinous carcinoma, and low-grade serous carcinoma. We studied the association of MMRD with clinicopathologic and immunohistochemical ...
Source: The American Journal of Surgical Pathology - Category: Pathology Tags: Original Articles Source Type: research
ra Maria Claudia Nogueira Zerbini Francisco Tibor Denes Ana Claudia Latronico Berenice Bilharinho Mendonca Madson Queiroz Almeida Antonio Marcondes Lerario Ibere Cauduro Soares Maria Candida Barisson Villares Fragoso Adrenocortical cancer is a rare malignant neoplasm associated with a dismal prognosis. Identification of the molecular pathways involved in adrenal tumorigenesis is essential for a better understanding of the disease mechanism and improvement of its treatment. The aim of this study is to define the prevalence of alterations in DNA mismatch repair (MMR) genes in Lynch syndrome among pediatri...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
We present a 47-year-old woman with an MLH1 gene mutation (G133X 397G>T) who presented with menorrhagia. Eleven family members have this mutation, 6 with carcinoma: 5 colorectal and 1 with a gynecologic primary of unknown type. Colonoscopy and endoscopy were unremarkable. Positron emission and computed tomography revealed a 3 cm anterior dome bladder mass without additional extrauterine disease or uterine connection. She underwent partial cystectomy, laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. The uterus demonstrated a dedifferentiated endometrioid adenocarcinoma, immunohistochemical...
Source: Applied Immunohistochemistry and Molecular Morphology - Category: Chemistry Tags: Online Articles: Case Reports Source Type: research
AbstractIndividuals who carry pathogenic mutations in DNA mismatch repair (MMR) genes have high risks of cancer, and small studies have suggested that these risks depend on the sex of the parent from whom the mutation was inherited. We have conducted the first large study of such a parent-of-origin effect (POE). Our study was based on all MMR gene mutation carriers and their relatives in the Colon Cancer Family Registry, comprising 18,226 people. The POE was estimated as a hazard ratio (HR) using a segregation analysis approach that adjusted for ascertainment. HR  = 1 corresponds to no POE and HR > ...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
Muir-Torre syndrome is a rare subtype of Lynch syndrome characterized by coincidence of skin neoplasm and visceral malignancies. Here, we report a case of this rare disease, whose diagnosis of the syndrome was first suspected by the pathologist. This was a 60-yr-old woman who presented with an axillary skin nodule, which was diagnosed as basal cell carcinoma. Further inquiry revealed that she was hospitalized for evaluation of a recurrent vaginal stump endometrial carcinoma. Histologic workup and immunohistochemistry for mismatch repair proteins of both the skin and vaginal tumor suggested the possibility of Muir-Torre syn...
Source: International Journal of Gynecological Pathology - Category: Pathology Tags: Pathology of the Corpus: Case Reports Source Type: research
Conclusions Lynch syndrome should be suspected in families with familial pancreatic cancer, even in the absence of colon cancers. Specifically, our observation supports the association between the MSH6 c.2194C>T pathogenic variant and extracolonic tumours and it suggests that MSH6 pathogenic variants are associated with familial pancreatic cancer more frequently than assumed.
Source: European Journal of Gastroenterology and Hepatology - Category: Gastroenterology Tags: Original Articles: Gastroenterology Source Type: research
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