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Query: UMLS:C0699790 (colon cancer)
 28,837 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

A kindred with the familial cancer syndrome is reported in which every confirmed affected member of the pedigree had at least one primary carcinoma of the colon. The average age at which cancer appeared was 38 years, and multiple primary neoplasm occurred in 23% of the cancer patients. Transmission of the cancer trait is consistent with an autosomal dominant mode of inheritance. Colonoscopy eliminated the presence of any unsuspected cancers in family members at risk. HLA typing was done, and by direct typing or inference, data were available on 66 living and deceased individuals. There were four informative matings in the kindred, the offspring of which showed only three crossovers of a possible 17. The lod score totaled 1.06 at a recombination fraction of 0.20. The need for cooperative efforts of many investigators in HLA linkage studies is emphasized, along with the potential value of such an approach.
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PMID:A linkage study of HLA and inherited adenocarcinoma of the colon. 723 94

Mutation of the APC gene may be a common denominator of all human colon cancer--polypoid and non-polypoid familial cancer as well as sporadic occurrences. Fearon and Vogelstein (1990) have described a series of molecular changes during the progression of human colon cancer, beginning with mutations in APC. Min is a strain of the laboratory mouse carrying a nonsense mutation in Apc, the mouse homologue of APC. The Min strain has been used to test the effect of germline alterations in certain genes identified in the progression pathway of Fearon and Vogelstein. A deficiency in DNA cytosine methylase leads to a reduction in the tumour multiplicity of Min mice contrary to the a priori expectation based on the global hypomethylation of the DNA of early colonic neoplasms. Alterations in Kras had no perceptible effect on the tumour multiplicity of Min mice but may not have been successfully directed to the proliferative cell population. Constitutional mutation of p53 did not influence the multiplicity or histopathology of early Min induced intestinal tumours. The cause and effect analysis of the genetics of colon cancer is clearly in an early phase. An unlinked genetic factor interacting with Min in controlling intestinal tumour multiplicity is Mom1. A central goal for the near future is to identify the Mom1 gene product and to identify other loci that can interact with the Min mutation and affect tumour multiplicity or progression. Mouse chimaeras will permit an analysis of the clonality and cell autonomy of Min induced neoplasms and also of the action of Mom1. The results of these analyses will inform investigators as to what modes of prevention and therapy might be designed for particular tumour types. The Min strain thereby presents an opportunity to discover protective factors against human colon cancer.
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PMID:Emergent issues in the genetics of intestinal neoplasia. 871 26

Although there has been much debate about the uptake and effects of predictive testing for common cancers, such as breast and colon cancer, little has been published on the more classical tumour predisposing conditions, such as von Hippel-Lindau disease and familial adenomatous polyposis. Since 1990 the genetics departments in Manchester and Cambridge have had a genetic register for cancer predisposing syndromes and presymptomatic testing for these conditions has been offered once this has become possible. To investigate the factors that might influence uptake of genetic testing in familial cancer syndromes we have reviewed our experience. Demand for predictive testing has generally been high, but men had a lower uptake (77%) than a comparable group of women (93%) (p < 0.01).
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PMID:Uptake of genetic testing for cancer predisposition. 932 61

We use the population-based Family-Cancer Database from Sweden to study familial breast cancer. The size of the population and the nation-wide registration of cancer offer unique possibilities for epidemiological studies of familial cancer, including complete and unbiased identification of cases in the probands and in their relatives, and complete and unbiased identification of the family relationships. Using the Database, we wanted to answer the following questions: (i) proportion of familial breast cancer among all breast cancers; (ii) familial relative risks in breast cancer alone or in combination with another cancer, defined either through the mother or the daughter; (iii) modification of familial risk by age; and (iv) effects of paternal breast cancer alone or in combination with maternal breast cancer. The proportion of familial female breast cancer among all breast cancers before 54 years of age in Sweden was 8.7%. The familial relative risk was about 1.8, but is likely to decrease to about 1.5 in the ageing population. The higher familial relative risks were evident in young women, being 4.0 when both the mothers and their daughters were diagnosed at ages <40 years. Paternal breast cancer, in combination with maternal breast cancer, caused a large (but not statistically significant) risk in the daughters. In mothers and daughters, ovarian but not colon cancer was increased in combination with breast cancer.
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PMID:Familial breast cancer in the family-cancer database. 966

The Diet, Activity, and Reproduction in Colon Cancer (DARCC) study is a large, multi-center case-control study of colon cancer. We examined family histories of cancer among first-degree relatives obtained by computer-assisted in-person interviews from the DARCC to study the impact of family histories of several cancers and colorectal polyps on colon cancer risk. We examined familial cancer risks both by treating a family history of polyps or cancer as a covariate in a logistic regression model, and by comparing cancer or polyp incidence among relatives of cases to incidence among relatives of controls in a proportional hazards model. There were few differences between the odds ratios (OR) or confidence intervals (CI) generated from logistic regression models and the hazard rate ratios (HRR) generated from the proportional hazards models. Overall, the OR of colon cancer among subjects with a family history of colorectal cancer was 1.77. There were only minor differences in risk by sex, age and subsite. A family history of colorectal polyps also increased risk by about the same amount as a family history of colorectal cancer. The increased risk associated with a family history of polyps did not appear to decrease with age.
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PMID:Risk of colon cancer associated with a family history of cancer or colorectal polyps: the diet, activity, and reproduction in colon cancer study. 975 45

Both environmental factors and an inherited predisposition influence carcinogenesis. The direct role of inheritance in the development of cancer is evident in familial cancer syndromes. These syndromes predispose to cancer through the inheritance of a mutation in a single gene in affected carriers. While many inherited cancer syndromes are rare, an inherited predisposition is directly responsible for 5%-10% of all colon and breast cancers. Complex multigenic inheritance plays an important role in cancer predisposition for the population at large. The identification of genes responsible for an inherited predisposition to colon and breast cancer syndromes has directed public attention to genetic testing for susceptibility to cancer. Assays are currently available to determine individual susceptibility to specific cancers. Cancer genetic testing is currently a time-consuming and complex procedure which requires expertise in its application, interpretation, and follow-up strategic planning. This review discusses cancer genetics and its application to individual and family cancer risk assessment with particular emphasis on breast and colon cancer.
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PMID:Genetic Testing for Cancer Risk Assessment: A Review. 1038 52

Scientific advances in cancer genetics, risk counseling, and management of high-risk individuals require information about familial cancer history. Because some people may not report, or may be unaware of, cancer in their families, it is important to examine the extent of underreporting of family history. We mailed a survey to first-degree relatives of patients with histologically confirmed diagnoses of colorectal cancer (CRC) before age 60 (n = 426, 77% response rate). Analyses examined the extent of underreporting of family history and its predictors (demographics, cancer characteristics, knowledge, and communication) and correlates (cancer worry, perceived risk). Logistic regression analysis was performed using generalized estimating equations to account for family clusters. Despite confirmed diagnosis of CRC in a parent or sibling, 25.4% of respondents reported having no first-degree relative with colon cancer. In multivariate models, the most significant predictor of awareness of a relative's CRC was the stage-at-diagnosis; also, males and those with low knowledge about colon cancer were significantly less aware. Awareness of a relative's CRC was associated with higher cancer worry and risk perception, and being a college graduate contributed independently to increased risk perception. Sole dependence on mailed self-administered questionnaires may lead to substantial underreporting of familial colon cancers, especially those that are in situ or localized.
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PMID:Underreporting of family history of colon cancer: correlates and implications. 1042 2

In order to explore the possible role of E-cadherin in familial cancer, 19 familial breast cancer patients, whose tumours demonstrated loss of heterozygosity (LOH) at the E-cadherin locus, were screened for germline mutations. No pathogenic germline alterations were detected in these individuals. However, a somatic mutation was found (49-2A-->C) in one of the tumours. This tumour showed a pattern of both ductal and lobular histology. Another 10 families with cases of breast, gastric and colon cancer were also screened for germline mutations, and no mutations were found. A missense mutation in exon 12 of E-cadherin (1774G-->A; Ala592Thr) was previously found in one family with diffuse gastric cancer, and colon and breast cancer. An allelic association study was performed to determine whether the Ala592Thr alteration predisposes to breast cancer. In total, we studied 484 familial breast cancer patients, 614 sporadic breast cancer patients and 497 control individuals. The frequencies of this alteration were similar in these groups. However, a correlation between the Ala592Thr alteration and ductal comedo-type tumour was seen. These results, together with previously reported studies, indicate that germline mutations and, more commonly, somatic mutations in E-cadherin may have an influence on the behaviour of the tumours, rather than predispose to breast cancer.
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PMID:Low frequency of E-cadherin alterations in familial breast cancer. 1130 55

The CHK2 gene encodes a protein kinase that is important for the regulation of cell cycle arrest after DNA damage. CHK2 acts downstream of ataxia teleangiecstasia mutated (ATM), modulates the function of p53 and may help mediate cell cycle arrest at G2/M by phosphorylation of Cdc25C. Recently, the human homolog of the checkpoint kinase Cds1 (CHK2) has been suggested to be a tumor suppressor gene. Heterozygous germline mutations have been reported in Li-Fraumeni syndrome (LFS), a highly penetrant familial cancer phenotype, and in sporadic colon cancer. LFS is associated with the development of lymphoid malignancies, especially childhood ALL. Therefore, we analyzed the DNA from 143 lymphoid malignancies to determine whether they had mutations of the CHK2 gene. The 14 exons of CHK2 were studied by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and sequencing of aberrantly migrating bands. One missense mutation changing serine to phenylalanine (codon 428) in an evolutionarily highly conserved domain was found in a non-Hodgkin's aggressive lymphoma. Another point mutation in the non-coding region was identified in one of adult T-cell leukemias (ATL) samples. This result suggests that mutation of the CHK2 gene may rarely be involved in the development of selected lymphomas.
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PMID:Analysis of the CHK2 gene in lymphoid malignancies. 1169 18


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