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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several pre-malignant diseases are known to have a genetic etiology. This study focuses attention upon precancerous disorders wherein the mode of inheritance is either well established or wherein it remains unclear even though familial aggregation of the particular diseases have been amply documented. These conditions will be discussed as useful models for systematic investigations of the host etiologic component in carcinogenesis. Our survey of hereditary precancerous syndromes includes multiple polyposis of the coli, the multiple mucosal neuroma syndrome, the Cancer Family Syndrome, Sipple's syndrome, Von Recklinghausen's neurofibromatosus, the multiple nevoid basal cell carcinoma syndrome, tuberous sclerosis, familial cutaneous malignant melanoma, and carcinoma of the breast. We have emphasized the heterogeneous character of many forms of familial cancer. Familial breast cancer associations clearly show such heterogeneity, as do colon cancer syndromes. Certain of these precancerous states are characterized by phenotypes which are clinically apparent, polyposis coli being the classic example. Others, such as Sipple's syndrome are amenable to routine screening for biochemical markers. The bulk of putative genetic cancer-predisposing problems require further basic investigation of modes of inheritance. Cancer control may be enhanced through communication of useful genetic and diagnostic information to primary care physicians. Referral of cancer clusters of possible genetic etiology from clinicians to human geneticists facilitates the necessary basic research.
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PMID:Familial cancer syndromes: a survey. 40 22

The goal of this review is to demonstrate the effective interaction of epidemiologic methods and molecular genetics in the identification of familial cancer predisposition. The example involves a hospital-based population of childhood soft tissue sarcoma patients who were less than age 16 years at diagnosis at the University of Texas M. D. Anderson Cancer Center, Houston, Texas, in 1944 through 1976, had survived at least 3 years from diagnosis, and were diagnosed at least 5 years before the start of our study. Familial data were collected on the patients' offspring, full siblings, parents, aunts, uncles, and grandparents. The initial analysis revealed a small but significant cancer excess in first-degree relatives. Genetic analysis demonstrated that the cancer distribution in families could best be explained by a rare autosomal dominant gene with penetrance such that the risk of cancer by age 35 years was nearly 50%. Most of the evidence for a dominant gene came from nine kindreds. Laboratory investigation of fibroblasts from those kindreds provided an in vitro model of cellular immortalization and carcinogenesis. Germline mutations in the tumor suppressor gene p53 were found in two of the families, and studies are ongoing in the other kindreds. This review demonstrates the power of genetic epidemiologic methods to characterize statistically a cancer-predisposing gene and the application of molecular genetics to define the genetic defect.
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PMID:The Li-Fraumeni syndrome: from clinical epidemiology to molecular genetics. 153 34

Several familial cancer syndromes have been identified. The syndrome of sarcomas, breast cancer and other neoplasms, known as Li-Fraumeni syndrome, is characterized by several different neoplasms presenting at young ages with autosomal dominant transmission and a high incidence of second primaries. In this paper, we studied six generations (51 people) of the family of a 24-year-old man with osteogenic sarcoma of the mandible. Twelve malignancies in 11 people, including several rare tumors, were revealed. Mean age of presentation was 24 years old. Nine of the 11 patients died of disease. One developed a second primary. Two tumors presented in the head and neck. Transmission was autosomal dominant. The karyotypes of two family members were normal. Identification of Li-Fraumeni syndrome in a family is important in determining appropriate follow-up for the patient and family. Such families are models for studying carcinogenesis.
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PMID:Family cancer syndrome: a study of the kindred of a man with osteogenic sarcoma of the mandible. 224 14

The clinical significance of methanogenic bacteria in large-bowel carcinogenesis has not been established so far. As part of a screening study of a randomized population sample of 200 men and 200 women aged 50-59 years, the present breath methane study was designed to gain further information on methane excretion in relation to premalignant colorectal lesions, familial cancer disposition, and dietary fat and fiber. Testing for breath methane excretion did not contribute towards the identification of individuals with premalignant colorectal lesions and therefore should probably not be considered a screening tool.
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PMID:Epidemiology of polyps in the rectum and sigmoid colon. Evaluation of breath methane and predisposition for colorectal neoplasia. 371 88

The Basel Familial Cancer Registry was established in 1982. Detailed pedigree data are obtained from 200 cancer patients every year. Analysis of familial clustering is performed by comparing the tumor spectrum of different family groups defined by the probands' cancer sites and by comparing tumor incidence and spectrum in the families with tumor incidence and spectrum in the population (data from the population - based Basel Cancer Registry). A nonrandom distribution of cancer in first-degree relatives of cancer patients and significant familial cancer aggregations point to underlying genetic mechanisms. The association of cancer and minor anomalies in children points to common mechanisms of carcinogenesis and teratogenesis. Laboratory investigations revealed an impaired DNA-repair synthesis in lymphocytes of breast cancer patients and their relatives. Patients and their relatives are counselled. They show interest and cooperate well. An early detection program is being developed in colorectal cancer. Administrative work is centrally organized and the screening work is performed by the family physicians.
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PMID:The potential of the Familial Cancer Registry for anticancer research and medical practice. 375 47

Many cancers, in both children and adults, cluster in families. Collection and statistical analysis of pedigree data suggest that genetic mechanisms play an important role in most cancer types. This is illustrated in colorectal, breast, lung, ovarian, and childhood cancer. Pedigree data are consistent with the hypothesis that cancer is sometimes inherited in an autosomal dominant Mendelian fashion. These rare hereditary cancers might not be different pathogenetically from those arising sporadically. A two-stage model for carcinogenesis provides a framework for the understanding of both forms of cancer. The establishment of registries for familial cancer would be most helpful for cancer risk determinations, surveillance and management programs, identification of new cancer-prone genotypes and etiological family studies.
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PMID:Familial cancer: genetically determined? (review). 684 31

We report on the cases of two sisters with carotid body tumor (CBT) and present a literature review that assembles epidemiologic information on 88 familial and 835 nonfamilial CBT patients. The sex ratio (males/females) of 1.0 for familial CBT (0.7 for nonfamilial) and CBT reports with complete sibship information suggest autosomal dominant genetic transmission. As in other familial cancers, bilateral disease is significantly more frequent in familial (31.8% of cases) than in nonfamilial CBT (4.4%). However, there is no difference in age at diagnosis between familial and nonfamilial CBR. Thus, this adult-onset familial cancer does not completely fit the Knudson "two-step mutation" model of carcinogenesis. We also found that 6% of reported CBT patients developed second primary tumors, mostly other paragangliomas. This feature suggests that CBT may be part of a larger neurocristopathy syndrome of multiple tumors of cells of neural crest origin.
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PMID:Familial carotid body tumors: case report and epidemiologic review. 700 Mar 34

The study of rare families in which a variety of cancers occur, usually at an early age and with patterns consistent with a common hereditary mechanism, has contributed much to our understanding of the process of carcinogenesis. So far, genes identified as having a role in cancer predisposition in these families have also been important in the histogenesis of sporadic cancers. In the two most clearly defined cancer family syndromes, the Li-Fraumeni syndrome and Lynch syndrome II, the genes involved predispose to diverse but specific constellations of cancers. Genes associated with site-specific familial cancer clusters may also give rise to increased susceptibility to other cancers, and site-specific clusters may represent one end of a spectrum. A consistent feature of familial cancer syndromes is the variable expression within and between families. A challenge for the future will be to determine other factors which may interact with the principal genes involved, giving rise to this variability.
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PMID:Familial cancer syndromes and clusters. 798 44

Deletion of p53, which is an anti-oncogene located on chromosome 17p, was reported to be present at a high incidence in tumor cells of colorectal carcinoma, as well as osteosarcoma of the familial cancer syndrome. Mutations of the p53 gene were investigated in 59 surgical specimens of primary carcinomas of the urinary system from 57 patients, using the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis. The PCR products were sequenced using the dideoxy chain termination method or the DNA sequencer. The tumors examined were 20 transitional cell carcinomas (TCC) and 39 renal cell carcinomas (RCC). Mutations of the p53 gene were detected in 20.0% (4/20) of TCC and were present in 16.7% (1/6) of the tumors invading the muscular layer. In two patients with simultaneous double bladder TCC, the mutations were found only in the larger tumors. In RCC, mutations were detected in 7.7% (3/39) of patients. No significant correlation between the presence of the mutation and the clinicopathologic parameters was found in RCC except that the three tumors with p53 gene mutations were clear cell carcinomas. These results suggest that p53 gene mutations play a possible role in both carcinogenesis and progression of TCC, but the p53 gene mutations may not be significant in development of RCC.
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PMID:Mutations of the p53 gene in carcinomas of the urinary system. 810 52

A predisposing gene (BRCA-1) for breast and ovarian cancer has been located on chromosomal region 17q12-21. According to Knudson's hypothesis if this gene is a tumor suppressor gene, allelic losses would be found in tumors occurring in families with cancer aggregations. We studied 25 samples of both benign lesions and malignant tumors, from breast cancer site-specific families and other familial cancer aggregations. Allelic losses seem to be more frequent in tumors from breast site-specific families but also include the predisposing locus in other syndromes, suggesting a role of BRCA-1 in such families. Finding of allele losses near this locus in benign lesions suggests that such alterations may represent a first step in breast carcinogenesis. It is noteworthy that allele losses involve larger chromosome fragments in malignant tumors than in benign lesions where BRCA-1 is not lost, suggesting a similar mechanism for genomic deletion in the tumorigenesis of the colon and of the breast.
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PMID:Detection of allelic losses on 17q12-q21 chromosomal region in benign lesions and malignant tumors occurring in a familial context. 829 Feb 55


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