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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary nonpolyposis colorectal cancer (HNPCC), also termed Lynch syndrome, may account for as much as 10-15 percent of the total colorectal burden. Lynch syndrome I is characterized by site-specific colorectal cancer (CRC) with early (congruent to age 45) onset, predilection to the proximal colon (congruent to 70%), and a marked susceptibility to metachronous CRC (45% following hemicolectomy or segmental resection). Lynch syndrome II shows the same colonic features but includes an excess of extra-colonic CRCs, namely carcinoma of the endometrium, ovary, small bowel, stomach, pancreas and transitional cell carcinoma of the ureter and renal pelvis. These findings form the basis for our surveillance recommendations: full colonoscopy initiated at age 25 and repeated every other year, and, in Lynch syndrome II variant, biannual endometrial aspiration biopsy. Screening for the remaining cancer types is dependent upon the availability of screening modalities and the pattern of cancer expression within specific families. The excess of metachronous CRC mandates that subtotal colectomy be performed for any CRC. The lack of premonitory physical stigmata has forced clinicians to diagnose HNPCC based on the family history in concert with the natural history features of the cancer phenotype within the pedigree. Problems with this approach include variable gene penetrance, the fact that cancer affected may or may not be gene carriers, death of gene carriers prior to developing cancer, and difficulty with pathology verification of tumor site and type. Partial resolution of these problems is possible now that HNPCC has been linked to chromosomes 2p and 3p and the susceptibility gene at chromosome 2p has been cloned.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genetics, natural history, surveillance, management, and gene mapping in the Lynch syndrome. 767 41

Hereditary nonpolyposis colorectal cancer (HNPCC, synonyms: cancer family syndrome, Lynch syndrome) is characterized by the occurrence of colorectal cancer and other primary tumors in susceptible family members. Inheritance is autosomal dominant with high penetrance. Endometrial cancer is the most frequent extracolonic malignancy in gene carriers. The criteria for the diagnosis HNPCC include the occurrence of colorectal cancer in three close relatives. However, not only colorectal cancer but also endometrial cancer may indicate HNPCC. We present a family diagnosed as a probable HNPCC kindred after endometrial cancer was observed in four sisters. One of these patients and the father of the four sisters had had colorectal cancer. This kindred illustrates the importance of recording the family history in patients with endometrial cancer.
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PMID:Endometrial cancer in four sisters: report of a kindred with presumed cancer family syndrome. 806 41

Hereditary nonpolyposis colon cancer (HNPCC) is an autosomal dominant trait responsible for approximately 6% of colorectal cancers. Linkage of the HNPCC trait to the D2S123 locus on 2p15-16 has previously been reported in two families. This HNPCC locus is now designated "COCA1." We have tested seven Canadian HNPCC families, who have a variety of clinical presentations, for linkage to a panel of microsatellite polymorphisms in the vicinity of D2S123. One family was clearly linked to the COCA1 locus (LOD = 4.21), and a second family is likely to be linked (LOD = 0.92). In three families linkage was excluded. In the remaining two families the data were inconclusive. In the linked family, individuals with cancer of the endometrium or ureter share a common haplotype with 12 family members with colorectal cancer. This supports the suspected association between these extracolonic neoplasms and the HNPCC syndrome. In addition, five of the six individuals with adenomatous polyps (but no colorectal cancer) have the same haplotype as the affected individuals, while the sixth carries a recombination. One individual with colorectal cancer carries a recombination that places the COCA1 locus telomeric to D2S123. This study localizes the COCA1 gene to an 8-cM region that is consistent with the location of the hMSH2 gene. We also confirm that families presently classified as HNPCC are genetically heterogeneous.
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PMID:Hereditary nonpolyposis colon cancer: analysis of linkage to 2p15-16 places the COCA1 locus telomeric to D2S123 and reveals genetic heterogeneity in seven Canadian families. 819 29

Hereditary nonpolyposis colorectal cancer (HNPCC) dates to Warthin's description of family G, which he began studying in 1895. Warthin's observations were not fully appreciated until 1966 when two families with an autosomal dominant inheritance pattern of nonpolyposis colorectal cancer (CRC) and endometrial cancer were described. This condition was first termed the "cancer family syndrome" and was later renamed HNPCC. Some have proposed that HNPCC consists of at least two syndromes: Lynch syndrome I, with hereditary predisposition for CRC having early (approximately 44 years) age of onset, a proclivity (70%) for the proximal colon, and an excess of synchronous and metachronous colonic cancers and Lynch syndrome II, featuring a similar colonic phenotype accompanied by a high risk for carcinoma of the endometrium. Transitional cell carcinoma of the ureter and renal pelvis and carcinomas of the stomach, small bowel, ovary, and pancreas also afflict some families. Current estimates indicate that HNPCC may account for as much as 6% of the total CRC burden. There are no known premonitory phenotypic signs or biomarkers of cancer susceptibility in the Lynch syndromes. This report will summarize current knowledge, with emphasis on the manner in which this knowledge can be employed effectively for diagnosis and management of HNPCC.
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PMID:Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. 848 67

Familial ovarian cancer is described as a familial aggregation of ovarian cancer. The disease is heterogeneous, with at least three genotypes prodisposing to distinctive hereditary syndrome, site-specific ovarian cancer, wherein familial cancer risk is restricted to ovarian carcinoma; breast/ovary carcinoma syndrome, that is ovarian carcinoma in association with carcinoma of the breast; and Lynch syndrome II, characterized by hereditary nonpolyposis colorectal cancer with proximal colonic cancer predominance, endometrial carcinoma, and ovarian carcinoma. When a familial aggregation of ovarian cancer is observed, unaffected women in the family should have periodic gynecologic examinations, including cytologic and ultrasonographic, radiologic studies and magnetic resonance imaging, in an effort to detect preinvasive ovarian cancer. Until more reliable diagnostic methods are developed, however, the physician should consider the advisability of prophylactic oophorectomy and oral contraceptives when counseling women who have several close relatives with ovarian cancer.
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PMID:[Familial ovarian cancer, uterine cancer]. 853 42

Hereditary non-polyposis colorectal cancer (HNPCC) is characterised by a genetic predisposition to develop colorectal cancer at an early age and, to a lesser degree, cancer of the endometrium, ovaries, urinary tract, and organs of the gastrointestinal tract other than the colon. In the majority of families the disease is linked to mutations in one of the two mismatch repair genes, hMSH2 or hMLH1. We have found a novel hMLH1 nonsense mutation in a Swiss family with Lynch syndrome, which has been transmitted through at least nine generations. A different tumour spectrum of neoplasms of the skin, soft palate, breast, duodenum, and pancreas was observed in three branches of this family, where there was a virtual absence of colonic tumours. The hMLH1 mutation could not be detected in members of these branches suggesting that at least a second genetic defect predisposing to cancer is segregating in part of the kindred.
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PMID:Complex genetic predisposition to cancer in an extended HNPCC family with an ancestral hMLH1 mutation. 886 53

Hereditary nonpolyposis colorectal cancer (HNPCC), also termed Lynch syndrome, was originally called cancer family syndrome. Historically, in 1913 Aldred Warthin, a pathologist, published a family, now known as Family G, which had features of HNPCC. It was first delineated as a hereditary cancer syndrome in the mid-1960s by Lynch. There was an apparent autosomal dominant mode of inheritance of colorectal cancer and certain integral cancers, the most prominent of which was endometrial carcinoma. Prior to the discovery in 1993 and 1994 of genes (hMSH2, hMLH1, hPMS1, hPMS2) known as mis-match repair genes or mutator genes, the diagnosis of HNPCC rested exclusively upon evaluation of clinical findings in concert with a well-documented and extended pedigree. Thus, this disorder has evolved from a medical curiosity into a clinical syndrome wherein molecular biologists provided proof of its hereditary status. These discoveries should aid in elucidating its pathogenesis and carcinogenesis and in the next decade we likely will learn more about chemoprevention and surgical prophylaxis of HNPCC.
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PMID:Molecular genetics and clinical-pathology features of hereditary nonpolyposis colorectal carcinoma (Lynch syndrome): historical journey from pedigree anecdote to molecular genetic confirmation. 949 83

Endometrial cancer (EC) shares some environmental or genetic risk factors with colorectal cancer (CRC). It represents a risk factor for CRC. Furthermore, EC is the most frequent extracolonic neoplasm in HNPCC (hereditary nonpolyposis colorectal cancer) and, in this syndrome, it has the same inheritance pattern as CRC. Neoplastic family history and clinical features were evaluated in women with EC in a health care district (Pordenone Province) in Northeastern Italy from 1990 to 1995, to examine the proportion of patients with hereditary cancer and the relation with clinical characteristics of EC. We interviewed 215 patients with EC (average age 61 years, range 35-88) in relation with some risk factors (age, weight, diabetes, menstrual and reproductive pattern, synchronous and metachronous neoplasms) and we obtained their family pedigree. Twenty-nine patients (13.5%) had a CRC family history, 66 (30.7%) showed an aspecific cancer aggregation in their families and more than half (120, 55.8%) had a negative cancer family history. Family pedigrees were consistent with a dominant inherited cancer pattern in 8 patients (3.7%) belonging to the CRC-related family history group. A different pattern of family history distribution emerged in relation with age (< 55 vs. > or = 55, p < 0.001) and body mass index (BMI) (< 26 vs. > or = 26, p = 0.002). Patients with a CRC pedigree were more numerous in the younger group, in the group with lower BMI and in pre-menopausal women.
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PMID:Risk factors for endometrial cancer according to familial susceptibility. 963 90

Hereditary nonpolyposis colorectal cancer (Lynch syndrome) is an autosomal dominant disease caused by mutations in the mismatch repair genes in particular in MLH1, MSH2 and MSH6. The disease is characterized by the development of colorectal, endometrial cancer and several other cancers. There is evidence that the clinical expression of the disease varies from one country to another. This variation might affect not only the application of criteria proposed to identify families but also clinical risk factors reported to predict the outcome of genetic testing. Data on site of the cancer, age at diagnosis and pathology were collected from 155 families with suspected HNPCC known at the Korean and Dutch HNPCC registries. DGGE, SSCP and DNA-sequencing were performed to identify MSH2, MLH1 and MSH6 mutations. A total of 33 Korean and 42 Dutch families met the clinical criteria for HNPCC. Germline mutations in the MMR-genes were found in 23 Korean and 24 Dutch families. In families that met the Amsterdam criteria, and also in those associated with MLH1 mutations, more cancers of the stomach and pancreas were observed in the Korean families than in the Dutch HNPCC families; in relative terms, the incidence of cancers of the endometrium in the Korean families was lower. Multivariate analysis showed that an early age at diagnosis, and the occurrence of pancreatic cancer were independent predictive factors of germline mutations in MLH1, MSH2 and MSH6 in the Korean subset of families.
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PMID:Gene-environment interaction in hereditary nonpolyposis colorectal cancer with implications for diagnosis and genetic testing. 1040 64

Hereditary non-polyposis colorectal cancer (or Lynch syndrome) is an autosomal dominant disease in which early onset colorectal carcinomas aggregate in families together with tumours of other organs. The genetic basis of the syndrome has been clarified with the identification of mutations in several DNA mismatch repair genes (MSH2, MLH1, PMS1, PMS2 and MSH6). We describe the clinical features and molecular characterization of a large hereditary non-polyposis colorectal cancer family which has been followed for almost 10 years. The kindred showed a striking aggregation of colorectal tumours in 3 successive generations; most of these neoplasms developed before the age of 50 years and were localized in the proximal colon. Molecular tests (carried out in ten individuals) showed specific alterations at the MLH1 gene, consisting in the insertion of a T nucleotide between bases 2,269 and 2,270; the mutation caused frameshift of the open reading frame and synthesis of a polypeptide longer than normal. The only tumour that could be analysed was positive for microsatellite instability. Physicians should become more confident with hereditary tumours and their implications, which are not limited to a single individual but concern all family members at risk of cancer. This family approach is different, and requires more expertise than the traditional individual approach. Common problems encountered in Hereditary Non-polyposis Colorectal Cancer families include: A) poor collaboration of subjects at risk (a situation which may cause some conflict between the doctor's duty to inform patients about their risk of disease and the rights of patients to choose and decide about their health); B) definition of the most appropriate surveillance programme for a given family (how many investigations to propose to the patients, and how often); C) possible interaction between genes and environmental factors (for instance, a gene carrier--in this family--developed an endometrial carcinoma after standard tamoxifen adjuvant therapy for breast cancer).
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PMID:Clinical and molecular diagnosis of hereditary non-polyposis colorectal cancer: problems and pitfalls in an extended pedigree. 1057 66


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