Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Pat Price, Karol Sikora in Treatment of Cancer, 2020
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.
Gastrointestinal Cancer and Complementary Therapies
Mary J. Marian, Gerard E. Mullin in Integrating Nutrition Into Practice, 2017
The primary nonmodifiable risk factors include genetic predisposition, family history, age, race, and gender. Familial adenomatous polyposis (FAP) and Lynch syndrome, which are the most common of the familial colon cancers, account for 5% of CRC cases. FAP is caused by a genetic mutation located on chromosome 5, which results in numerous colonic adenomas (Burt et al., 1995). Lynch syndrome, which is also known as hereditary nonpolyposis colorectal cancer, is caused by a defect in the mismatch repair genes (Kempers et al., 2011). Ulcerative colitis, Crohn’s disease, acromegaly, renal transplantation, polyps, and abdominal radiation lead to an increased risk of CRC. African Americans have the highest rate of CRC of all ethnic groups. The risk of CRC begins to increase after 40 years of age and rises sharply at ages 50–55. Overall, CRC incidence and mortality rates are about 35%–40% higher in men than in women (Smith et al., 2001).
Gynecological Cancer—Ovarian, Endometrial, Cervical
Peter G. Shields in Cancer Risk Assessment, 2005
In 1990, Lynch et al. reported three separate hereditary ovarian cancer syndromes; site-specific ovarian cancer; hereditary ovarian and breast cancer; and Lynch type II or hereditary nonpolyposis colorectal cancer (HNPCC), (in which case there is an increased risk of ovarian, colorectal, endometrial, and/or genitourinary cancers) (15–18). All three syndromes are associated with an autosommal dominant pattern of inheritance with variable penetrance and early onset cancer (17,19,20). This means that each first-degree relative of an individual with a mutation has a 50% chance of inheriting it. Clues in a family history to suggest such a strong hereditary predisposition include; multiple cancers occurring in close relatives over multiple generations, early age of onset of cancer (i.e., before 40 or 50 years), multiple cancers occurring in a single individual and a pattern consistent with an autosommal dominant inheritance or a familial association with tumors of other organs, particularly the breast, colon, and uterus.
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.
Lynch syndrome and sextuple primary malignancies
Published in Acta Chirurgica Belgica, 2018
Donatas Danys, Eugenijus Stratilatovas, Vaidas Cereska, Tomas Poskus
Lynch syndrome (LS) or hereditary nonpolyposis colorectal cancer (HNPCC) is the most common of hereditary colorectal cancer and accounts for 1–3% [1], Lynch and Chapelle estimated that it accounts 5–8% for all colorectal cancers [2]. It is an autosomal dominant syndrome characterized by predisposition of various cancers (colorectal, stomach, endometrial, ovarian, renal, small bowel, hepatobiliary tract) [3,4] at earlier age than in general population [5] and occurs as a result of mutation in DNA mismatch repair genes. The most common are: MLH1, MSH2, MSH6, and PMS2 [6]. Approximately 70% of LS is caused by MLH1 and MSH2 mutations [7].
Risk of colorectal polyps and of malignancies in asymptomatic carriers of mutations in the main DNA mismatch repair genes
Published in Scandinavian Journal of Gastroenterology, 2018
Maurizio Ponz de Leon, Monica Pedroni, Annalisa Pezzi, Blerta Sulce, Luca Roncucci, Federica Domati, Giuseppina Rossi, Luca Reggiani Bonetti
In contrast, mutation carriers in the DNA mismatch repair genes, who are predisposed to Lynch syndrome (hereditary nonpolyposis colorectal cancer), usually remain completely asymptomatic (i.e., perfectly normal individuals) for several years, and cancer (or polyp) occurrence cannot be predicted with certainty, despite the mutation. The reasons for this reduced penetrance are still poorly defined and are probably a result of environmental, hereditary or a mixture of both influences [6,7].
Related Knowledge Centers
- Brain Tumor
- Colorectal Cancer
- Endometrial Cancer
- Gallbladder Cancer
- Gastrointestinal Cancer
- Skin Cancer
- Stomach Cancer
- Ovarian Cancer
- Urinary System
- Dominance