China
Africa
Explore chapters and articles related to this topic
Genomic Informatics in the Healthcare System
Published in Salvatore Volpe, Health Informatics, 2022
One unique feature of genomic medicine studies is the potential for genetic risks identified within an individual to affect the care of family members through cascade testing of relatives. For the family outcome, clinical outcome studies would test first- and second-degree family members of study participants with a pathogenic variant and track family members with the consent of the patient and family member for changes in healthcare delivery and clinical outcomes. Given that family members are much more likely than average to also have the variant, cascade testing will increase the efficiency of the study and health effect of the original finding. This increased efficiency has been shown in the context of screening patients with colorectal cancer to identify Lynch syndrome. In practice, investigators need to plan to overcome logistical and health policy hurdles to cascade testing.
Case 14
Published in Andrew Solomon, Julia Anstey, Liora Wittner, Priti Dutta, Clinical Cases, 2021
Andrew Solomon, Julia Anstey, Liora Wittner, Priti Dutta
Lynch syndrome (hereditary non-polyposis colorectal cancer)Autosomal dominant disorder caused by mutations in MLH1, MSH2, MSH6 or PMS2 genesExtremely high lifetime risk of colorectal cancer, but also high risk for hepatobiliary, endometrial, ovarian and gastric cancers
Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Robert D. Morgan, Andrew R. Clamp, Gordon C. Jayson
Loss-of-function mutations in genes involved in the MMR pathway lead to microsatellite instability and are associated with Lynch syndrome (hereditary nonpolyposis colorectal cancer). Germline mutations in genes involved in MMR, in particular MLH1, MSH2, MSH6, and PMS2, are associated with <3% of all ovarian cancer cases. Cases of Lynch syndrome–associated ovarian cancer more frequently include endometrioid or clear cell subtypes, well- or moderately differentiated tumors, and early-stage disease. Women with germline mutations in MLH1, MSH2, and MSH6 have a lifetime risk of ovarian cancer between 10% and 17%.24 Other cancers related to Lynch syndrome include colorectal, gastric, pancreatic, ureteral and renal pelvis, biliary tract, and brain. It is important to note that most women diagnosed with hereditary ovarian cancer present at a younger age compared with sporadic cases.
Triumph against cancer: invading colorectal cancer with nanotechnology
Published in Expert Opinion on Drug Delivery, 2021
Preksha Vinchhi, Mayur M. Patel
Approximately, 70–80% of CRCs are sporadic which typically results from mutations that affect Wnt/β catenin signaling pathway. Remaining 20–30% of CRC cases account for hereditary CRC which includes hereditary nonpolyposis CRC/Lynch syndrome (2–4%), familial adenomatous polyposis (FAP) (1%) and MUTYH associated polyposis (MAP) (1%). Lynch syndrome is caused because of mutation in the genes involved in DNA mismatch repair, e.g. MutL homolog 1(MLH 1), MutS protein homolog 2(MSH 2), MutS protein homolog 6 (MSH 6), Mismatch repair endonuclease (PMS2) and epithelial cell adhesion molecule (EpCAM). Whereas FAP is caused by mutations in adenomatous polyposis coli (APC – a tumor suppressor gene). Juvenile polyposis, peutz jeghers disease, muir torre syndrome, Cowden disease are some of the rare hereditary syndromes [13].
Upregulation of TIGIT and PD-1 in Colorectal Cancer with Mismatch-repair Deficiency
Published in Immunological Investigations, 2021
Xuebing Zhou, Xiaoling Ding, Hai Li, Chun Yang, Zhanbing Ma, Guangxian Xu, Shaoqi Yang, Dong Zhang, Xiaoliang Xie, Lei Xin, Xiaoli Luo
CRC is a cancer with a poor prognosis. dMMR is common in CRC and is associated with an even poorer prognosis (Clark et al. 2004). In addition, the dMMR phenotype has therapeutic implications (O’Kane et al. 2017). Lynch Syndrome is caused by mutations in the genes involved mismatch repair and is the cause of 2%-12% of CRCs (Moreira et al. 2012; Mork et al. 2015; O’Kane et al. 2017). Despite great efforts to develop effective anti-cancer treatments, there has been little progress in the prognosis of CRC during the past decades. TIGIT regulates the immune response (Stanietsky et al. 2009; Stengel et al. 2012; Yu et al. 2009). PD-1 is involved in the immune escape mechanisms of solid tumors (Ahmadzadeh et al. 2009; Blank and Mackensen 2007; Grosso et al. 2007; Sakuishi et al. 2010). Their combined role in colorectal cancer is unknown. Therefore, this study aimed to examine the role of TIGIT and PD-1 in patients with CRC and on the function of activated T cells. The results strongly suggest that TIGIT and PD-1 are upregulated in CRC with dMMR tissues. TIGIT and PD-1 expression was associated with the TNM stage and DFS.
The Potential for Reducing Lynch Syndrome Cancer Risk with Nutritional Nrf2 Activators
Published in Nutrition and Cancer, 2021
Lynch Syndrome (LS), also known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant cancer susceptibility syndrome that increases the risk of multiple cancers including colorectal (CRC), endometrial, ovary, stomach, ureter, renal pelvis, brain, small bowel, and hepatobiliary tract (1, 2). LS is the most common heritable CRC syndrome and is suggested to be responsible for 2% to 4% of all CRC cases in the Western world (3). Mutations in four mismatch repair (MMR) genes have been identified as causative for LS: Mut L homolog (MLH1); Mut S homologs (MSH2 and MSH6); and postmeiotic segregation, a Mut L homolog (PMS2). Combined, MSH2 and MLH1 are associated with approximately 85% of LS cases with MSH6 and PMS2 accounting for approximately 15% of cases (2). LS mutations alter the function of MMR proteins, increasing the carrier’s DNA susceptibility to replication errors and cellular stressors including oxidative stress (OS). Ultimately, this increases the likelihood of cellular DNA mutations and the formation of cancerous cells.