China
Africa
Explore chapters and articles related to this topic
Clinical Cancer Genetics
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Rosalind A. Eeles, Lisa J. Walker
Hereditary cancer pre-disposition genes have also been divided into “gatekeeper genes” and “caretaker genes.” “Gatekeeper” genes are those that regulate progression through the cell cycle. Disturbance of their function leads to an imbalance of cell division over cell death. This cellular proliferation is followed by the accumulation of multiple somatic genetic events leading to the tumor. Examples of “gatekeeper” genes include RB1 and TP53. “Caretaker” genes maintain the integrity of the genome. Mutation occurring in these genes simply gives rise to genetic instability, causing mutation in other genes, including “gatekeeper” genes. The DNA mismatch repair genes causing HNPCC are examples of “caretaker” genes.
Colon cancer: pathology and natural history
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
HNPCC was first described in 1913 by Aldred Warthin24, and more recently was the subject of intensive clinical study by Henry Lynch and colleagues25. In fact, the syndrome is often referred to by the eponym of Lynch syndrome. In HNPCC kindreds, cancer susceptibility is inherited in autosomal dominant fashion and is evidenced by the development of cancers, of which the most common is colon cancer of the right colon. A set of clinical criteria for recognizing HNPCC kindreds, known as the Amsterdam criteria, is reported in Table 2. In addition, HNPCC is classified into two Lynch syndromes (Table 2). These criteria, although useful, are highly stringent and certainly, in some cases, fail to identify families with HNPCC. Despite the term HNPCC, however, current evidence suggests that adenomatous polyps are in fact present as precursors to the colon cancers that develop in this syndrome. It seems that the rate of malignant transformation of such polyps is dramatically faster than that of typical sporadic adenomatous polyps26. Affected individuals in HNPCC kindreds also show a clearly elevated incidence of endometrial and gastric cancers (Table 2).
Hereditary Colorectal Cancer
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Lynch Syndrome (LS) is a predisposition to early onset multiple cancers of multiple organs, but especially the colon and rectum. This predisposition is due to germline mutation of DNA mismatch repair genes (and EPCAM). The pathology professor Aldred Warthin from Michigan brought the syndrome to light initially after being introduced to a large affected family by his seamstress. Warthin’s concept of hereditary cancer remained hidden however, until uncovered 50 years later by a medical oncologist from Creighton University called Henry Lynch. Having discovered Warthin’s original family, Lynch wrote about ‘cancer family syndrome’, and added two new families of his own. Rick Boland applied the names Lynch Syndrome I and II depending on whether the pattern of the disease was colorectal cancers alone or in combination with cancers of other organs, but Lynch preferred the term Hereditary Non-Polyposis Colorectal Cancer (HNPCC) to distinguish the syndrome from polyposis. In 2006 the term Lynch Syndrome was resurrected140 and applied only to patients and families that have a germline mutation that abrogates DNA mismatch repair.141,142
The factors associated with distress a minimum of six months after BRCA1/2 confirmation: A systematic review
Published in Journal of Psychosocial Oncology, 2021
Ellen Butler, Sonya Collier, David Hevey
Despite the variety of outcome measures for measuring distress included in this review, the overall findings indicate that most BRCA1/2 carriers experience an initial increase in generalized distress after results disclosure, which than returns to approximate pretesting levels six to twelve months afterwards.5,6,21,31,33,38 These findings are supported by a previous meta-analysis,46 systematic review3 and in studies examining distress levels for other genetic cancers such as hereditary nonpolyposis colorectal cancer (HNPCC).47 A potential explanation for the increase in distress at time of results disclosure is the number of complex decisions BRCA1/2 carriers are likely to face at this time regarding treatment options, communication to family and friends and personal adjustment. This increase is in line with research on the limited impact of stressful life events.48 However, another study reported that mean anxiety and depression levels increased significantly in BRCA1/2 carriers and non-carriers from 1 year to approximately 5 years after testing but remained below clinical cutoff points.36 The authors suggested that this increase in distress may be associated loss experiences and warrants further research.
A Comparison of Emergency First Presentations of Colorectal Cancer in Under–50 and Over–50 Year-Old Patients
Published in Journal of Investigative Surgery, 2020
Prateush Singh, Krashna Patel, Pallavi Arya, Esha Singh, Amitabh Mishra
It is often believed that young patients with advanced presentations of CRC have a genetic predisposition. In our study, 32% had a first-degree relative with CRC which is higher than most other studies. However, postoperative genetic analysis revealed genotypes consistent with HNPCC in only 13.6%. Myers et al. report a 12% incidence of family history in under-50s [4] and an estimated 15%–20% of all patients with CRC have a positive family history [17]. This is consistent with other studies that most patients with CRC, regardless of age, will have sporadic disease. None of the patients presenting as emergencies were known to have underlying risk factors such as inflammatory bowel disease or underling genetic conditions prior to presentation. Such patients undergo routine colonic surveillance and are aware of the clinical presentation of CRC and are likely to be managed electively.
Proteogenomic biomarkers in colorectal cancers: clinical applications
Published in Expert Review of Proteomics, 2020
Margherita Binetti, Augusto Lauro, Samuele Vaccari, Maurizio Cervellera, Valeria Tonini
In this setting, biological biomarkers could be used to differentiate between sporadic and hereditary cancer [5]. Among hereditary conditions, different elements have been described, such as the Familial Adenomatous Polyposis (FAP), and the Hereditary Non-Polyposis Colon Cancer (HNPCC), also known as Lynch Syndrome [48]. The FAP is an autosomal disorder, involving the APC gene, part of Wnt/beta-catenin pathway [49], while the Lynch Syndrome is the most frequent syndromic disease associated with CRC, representing 3% of new diagnoses [50]. It is a genetic condition due to DNA mismatch repair (MMR), expressed by few gene mutations responsible for error accumulation in DNA. In specific, the MLH1 gene (50%), MSH2 (40%), MSH6 genes (7%–10%), and PMS2 gene (5%) are often involved [5]. Finally, the PJS is also related to an increased cancer risk, which has been related to P53 pathway. The P53 activity test could be useful in the clinical management of the disease [51]. There are also some other inherited syndromes, such as MUTYH-associated polyposis and Cowden/PTEN hamartoma syndrome [52].