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Results for “Cancer genetics”

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At least 739 records · Page 41Linked to original sources
PubMed2004

[BRCA1 and BRCA2 have reached the clinical medicine. The 10-year old finding of the genetic mutation makes it now possible to prevent breast cancer].

Increased knowledge of breast cancer genetics has improved the possibilities to predict the future risk of a woman to be diagnosed with breast cancer. In certain families, presymptomatic testing of breast cancer susceptibility genes may be offered, leading to an even more accurate individual risk prediction. As a result, advice regarding follow-up and risk reducing measures may be given to the individuals with the highest risks of cancer. Preventive surgery drastically reduces the risk of having breast or ovarian cancer respectively. The value of increased controls in hereditary high risk women is insufficiently investigated. Further studies are warranted to elucidate the efficacy of chemoprevention in women at a very high risk of breast cancer, e.g. mutation carriers of BRCA1 and BRCA2.

Breast Neoplasms↗
PubMed1995

Molecular genetics of lung cancer.

The identification of genetic abnormalities in lung cancer and their consequences for cell growth, differentiation and function offer insights into normal cellular function and carcinogenesis. The integration of this knowledge with data from other fields, including epidemiology, toxicology, carcinogen metabolism, clinical genetics and clinical cancer therapy, promises advancements in lung cancer risk assessment, screening, prevention, prognostic assessment and therapy.

Animals↗
PubMed1998

Analysis of HLA-DRB1-related alleles in Japanese patients with lung cancer--relationship to genetic susceptibility and resistance to lung cancer.

PURPOSE: To investigate differences in HLA status among lung cancer patients, patients with hematological malignancies, and healthy controls in order to determine the genetic susceptibility and resistance features of HLA-DRB1-related alleles in Japanese patients with lung cancer. METHODS: HLA class I (HLA-A, -B, and -C) antigens and HLA class II (HLA-DRB1) alleles were determined in 36 patients with lung cancer, 35 patients with hematological malignancies, and 90 healthy controls. HLA class I status was investigated by serological techniques, and HLA class II by polymerase chain reaction/restriction-fragment-length polymorphism analysis. RESULTS: Lung cancer patients showed an increased frequency of HLA-DRB1*0901, and a decreased frequency of HLA-DRB1*1302 and DRB1*14-related alleles when compared to the other subjects. CONCLUSION: These results suggest that genetic factors influence the susceptibility and resistance to lung cancer. However, this study should be considered preliminary because of the relatively small number of patients examined and the possibility of racial differences in HLA status of lung cancer patients between Japan and other countries.

Adult↗
PubMed2004

Defective DNA strand break repair after DNA damage in prostate cancer cells: implications for genetic instability and prostate cancer progression.

Together with cell cycle checkpoint control, DNA repair plays a pivotal role in protecting the genome from endogenous and exogenous DNA damage. Although increased genetic instability has been associated with prostate cancer progression, the relative role of DNA double-strand break repair in malignant versus normal prostate epithelial cells is not known. In this study, we determined the RNA and protein expression of a series of DNA double-strand break repair genes in both normal (PrEC-epithelial and PrSC-stromal) and malignant (LNCaP, DU-145, and PC-3) prostate cultures. Expression of genes downstream of ATM after ionizing radiation-induced DNA damage reflected the p53 status of the cell lines. In the malignant prostate cell lines, mRNA and protein levels of the Rad51, Xrcc3, Rad52, and Rad54 genes involved in homologous recombination were elevated approximately 2- to 5-fold in comparison to normal PrEC cells. The XRCC1, DNA polymerase-beta and -delta proteins were also elevated. There were no consistent differences in gene expression relating to the nonhomologous end-joining pathway. Despite increased expression of DNA repair genes, malignant prostate cancer cells had defective repair of DNA breaks, alkali-labile sites, and oxidative base damage. Furthermore, after ionizing radiation and mitomycin C treatment, chromosomal aberration assays confirmed that malignant prostate cells had defective DNA repair. This discordance between expression and function of DNA repair genes in malignant prostate cancer cells supports the hypothesis that prostate tumor progression may reflect aberrant DNA repair. Our findings support the development of novel treatment strategies designed to reinstate normal DNA repair in prostate cancer cells.

Animals↗
PubMed1994

[Genetics and cancer of the breast].

Breast carcinoma is the commonest cancer in women. Segregation analyses support the existence of a major susceptibility gene with a dominant pattern of inheritance in 4 to 10% of cases. Three genes involved in the genetic predisposition to breast tumors have recently been identified: BRCA-1 associated with early onset familial breast cancer and breast/ovarian carcinoma syndrome, p53 associated with Li-Fraumeni syndrome, and the androgen receptor gene in male breast cancer with Reinfenstein syndrome. A better understanding of inherited contribution may have important implications for screening individuals at high-risk in families.

Ataxia Telangiectasia↗
PubMed1999

Genetic and epigenetic contributions to colorectal cancer.

Both genetic and epigenetic factors contribute to the development of colorectal cancer. Specific genetic changes in proto-oncogenes, tumor suppressor genes, and DNA mismatch repair genes have led to a genetic model of colorectal tumorigenesis. Recent data highlight the importance of the TGF-beta signaling pathway in regulating the progression of colorectal cancer. The loss of the tumor suppressor activity of this pathway as well as the potentially cooperative genetic aberrations involving APC, K-ras, and p53 are reviewed in the context of the multi-step adenoma-carcinoma sequence that characterizes the development of colorectal tumorigenesis. In addition, contributing epigenetic factors including age, diet, angiogenesis, and immune response are also discussed. Combining our knowledge of the genetic and epigenetic events implicated in this disease may allow a broader understanding of the pathogenesis of colorectal cancer and hence the design of better anti-tumor interventions.

Animals↗
PubMedDate not supplied

[Genetics and cancer].

Explore the source record for details and available documents.

Chromosome Aberrations↗
PubMed2004

Healthy women from suspected hereditary breast and ovarian cancer families: the significant others in their lives.

This paper investigates communication and interactions between healthy women from families with a history of breast/ovarian cancer and five statuses of significant others: (1) women friends; (2) sisters; (3) brothers; (4) male partners; and (5) children in order to better understand the way the family deals with cancer genetics risk information and the extent of social support available to its members. We conducted a research ethics committee reviewed exploratory, qualitative study at a major clinical and research cancer centre in the United Kingdom from January to June 2000. Twenty-one semi-structured, in-depth interviews were conducted using a purposive sample of women coming to the cancer genetics risk clinic for the first time, supplemented by 5 months of participant observation. On the whole, women friends consistently provided strong social support. Sisters were usually close, but communication about the breast/ovarian cancer in their family in some cases was quite limited and fraught with emotional overtones. Brothers were the most difficult to relate to regarding cancer in the family and seemed almost to exist in a different 'interrelational space'. The women claimed that their male partners were supportive, but with caveats. Mothers worried about how much information and at what age they should inform their children about the specifics of the family history of breast/ovarian cancer and tried to protect them when they were young. The women were very concerned about their daughters and granddaughters, but were far less concerned about the impact on their sons.

Adult↗
PubMed1989

The emerging genetics of cancer.

The rapid progress in molecular biology has allowed investigators to define some of the basic mechanisms of carcinogenesis. At the molecular level, cellular transformation results from the occurrence of two or three distinct genetic events that uncouple the cell from its normal regulatory mechanisms. One family of genes, the oncogenes, may be particularly important in the process. The aberrant expression of oncogenes, either by mutation or simply by increased transcription, may result in cellular transformation. The genes usually code for growth factors, growth factor receptors or for proteins involved in the transduction of growth signals into the nucleus. Genetic activation causes the cell to continuously sense a message to undergo mitosis, and the cell no longer responds to its normal regulatory signals. The concepts are rapidly moving into the clinical realm as the genetic mechanisms of particular neoplasms have been investigated. The neuroblastoma is the first tumor system in which the biologic characteristics of the tumor were found to be related to a known oncogene; the amplification of the myc gene is an independent marker of the aggressiveness of the tumor. In addition, much progress has been made in defining the specific genetic lesions responsible for retinoblastomas, Wilms' tumors and carcinomas of the colon that arise in patients with familial polyposis coli. As more knowledge accumulates regarding the exact mechanisms through which the proteins encoded by oncogenes affect these carcinomas and others, it may become possible to design pharmacologic agents rationally to hinder their growth selectively.

Humans↗
PubMedDate not supplied

The genetics of cancer susceptibility: from mouse to man.

Cancer affects approximately 1 in 3 individuals. An individual's susceptibility to cancer is partly determined by environmental exposures and by the combination of inherited cancer susceptibility and resistance genes. Initial mapping of these low penetrance cancer susceptibility genes has been done in the mouse because human low penetrance genes are extremely difficult to find using traditional methods due to heterogeneity and interacting factors. Also, the choice of candidate genes for human association studies can miss the unknown or unexpected. Mouse models also have limitations; it can be difficult to identify causal polymorphisms in the mouse because linkage disequilibrium often extends across several genes. To exploit the strengths of both systems, we outline a cross-species strategy to identify human variants associated with increased cancer risk. This approach uses linkage analysis and haplotyping, allelic imbalance in tumors, and gene expression studies in the mouse, combined with association studies and tumor imbalance studies in humans to identify causal cancer susceptibility variants. Allelic variants in both mouse and human can then be used to better understand the mechanisms behind cancer risk and as targets for intervention.

Alleles↗
PubMed2004

Genetic variation in cancer predisposition: mutational decay of a robust genetic control network.

A computational model of cancer progression is used to study how mutations in genes that control tumor initiation and progression accumulate in populations. The model assumes that cancer occurs only after a cell lineage has progressed through a series of stages. The greater the number of stages, the more strongly the individual is protected against cancer. It is shown that an extra stage initially improves the survival of individuals by decreasing mortality from cancer. However, the additional buffering by an extra stage reduces the impact of any single hereditary mutation and therefore allows the accumulation of more nonlethal mutations in the population. Extra stages thereby lead to the evolution of partially decreased cancer mortality and significantly increased genetic predisposition to disease in the population as a whole. In general, the model illustrates how all robust control networks allow the accumulation of deleterious mutations. An increase in the number of buffering components leads to significant mutational decay in the protection provided by each buffering component and increased genetic predisposition to disease. An extra buffering component's net contribution to survival and reproduction is often small.

Aging↗
PubMed2004

Genetically targeted cancer therapy: tumor destruction by PKR activation.

The is a double-stranded RNA-activated protein kinase (PKR) has been largely investigated for its key role in viral host defense. Although best characterized by its function in mediating the antiviral and antiproliferative effects of interferon (IFN), PKR is also implicated in transcriptional regulation, cell differentiation, signal transduction, and tumor suppression. However, recent findings identifying PKR as an important effector of apoptosis have led to an increased interest in PKR modulation as an antitumor strategy. PKR can either be up-regulated through direct induction by the transcription factor E2F-1, or it can be activated through direct protein-protein interactions with the melanoma differentiation-associated gene-7 (MDA7, IL-24). Additionally, the intracellular formation of double-stranded RNA by transfection with antisense RNA complementary to tumor-specific RNA sequences can induce PKR activation and apoptosis selective to these tumor cells. The growing application of viral vector-based gene therapies and oncolytic, replicating viruses that must elude viral defense in order to be effective, has also drawn attention to PKR. Oncolytic viruses, like the attenuated herpes simplex virus R3616, the vesicular stomatitis virus, or reovirus, specifically replicate in tumor cells only because the viral host defense in the permissive cells is suppressed. In this article we review the role of PKR as an effector of apoptosis and a target for tumor treatment strategies and discuss the potential of PKR-modifying agents to treat patients with cancer. Targeted gene therapy against cancer can be approached by activation of PKR with the down-regulation of protein synthesis and induction of apoptosis, or by suppression of PKR with the propagation of oncolytic virus. Since the PKR pathway can be modified by many routes, antitumor therapies combining oncolytic virus, gene therapies, and chemotherapy with PKR modifiers are likely to emerge in the near future as therapeutic options in the treatment of patients with cancer.

Animals↗
PubMed2004

Measuring the genetic damage in cancer patients during radiotherapy with three genetic end-points.

In this paper the genetic damage for three genetic end-points was studied in cancer patients during radiotherapy using the micronucleus test, comet assay and hprt gene mutation test. The subjects were from: (i) a group of 24 patients suffering from various types of cancers; (ii) a group of 23 controls matched according to age, sex and smoking. Blood samples were collected from the controls and from the cancer patients prior to radiotherapy and after cumulative radiation doses of 10, 30 and 50 Gy. The results of the micronucleus test indicated that the mean micronuclei rate (MNR) and mean micronucleated cells rate (MCR) in the cancer patients prior to radiotherapy were 12.46 and 11.29 per thousand, respectively, which were significantly higher than those (6.65 and 5.96 per thousand) in controls (P < 0.01). However, the results of the comet assay and hprt gene mutation test showed no significant difference between untreated cancer patients and controls (P > 0.05). The mean MNR/MCR at 0, 10, 30 and 50 Gy in cancer patients increased with the cumulative dose, being 12.46, 35.83, 64.63 and 85.00 per thousand for MNR and 11.29, 31.25, 53.63 and 67.28 per thousand for MCR, respectively. Similar results were obtained in the comet assay and hprt gene mutation test. Meanwhile, it was found that there was inter-individual variability in response to radiotherapy among patients.

Adult↗
PubMed2002

Familial cancer aggregation and the risk of lung cancer.

CONTEXT: Around 90% of lung cancer worldwide is attributable to cigarette smoking, although less than 20% of cigarette smokers develop lung cancer. Other factors such as diet, chronic lung diseases, occupation and possibly environmental agents also contribute to this cancer. Genetic factors seem to play a role in lung cancer, but the precise characteristics influencing lung cancer susceptibility are not known, since genetic factors are easily obscured by the strong environmental determinants of lung cancer, particularly smoking. OBJECTIVE: To estimate the effect that cancer occurrence among first-degree relatives has on the risk of lung cancer. DESIGN: Hospital-based case-control study. SETTING: The metropolitan region of São Paulo, Brazil. PARTICIPANTS: 334 incident lung cancer cases and 578 controls matched by hospitals. MAIN MEASUREMENTS: By means of a structured questionnaire, cases and controls were interviewed about cancer occurrence in first-degree relatives, tobacco smoking, exposure to passive smoking, occupation, migration and socioeconomic status. Non-conditional logistic regression was used to calculate the risk of familial cancer aggregation, the effect of cancer in first-degree relatives and smoking in conjunction, and for controlling confounders. RESULTS: The adjusted odds ratio (OR) revealed a slight, but not statistically significant, excess risk of lung cancer for subjects with a history of lung cancer in relatives (OR 1.21; 95% confidence interval [CI] 0.50 - 2.92). The same was found among those with a history of other tobacco-related cancers in relatives (OR 1.36; 95% CI 0.87 - 2.14). A step gradient effect was observed regarding lung cancer risk, in accordance with increases in the number of pack-years of cigarette consumption. An interaction between familial cancer aggregation and tobacco smoking was detected. CONCLUSIONS: A mildly elevated risk of lung cancer among persons with a positive history of lung and other tobacco-related cancers was observed. The finding of an interaction between the variables of familial cancer aggregation and smoking suggests that familial cancer aggregation could be considered as a marker of susceptibility, increasing the risk of lung cancer among smokers. These results improve our knowledge of lung carcinogenesis and can guide future cancer genetic studies.

Adult↗
PubMed2005

Repositioning the patient: the implications of being 'at risk'.

In the modern era of biomedical practice, genetic knowledge has redefined the idea of 'the patient' to include those who are 'at risk' of disease alongside those who are already sick. For such individuals, it is risk itself that constitutes the raison d'être of medical intervention. Using data from interviews with 58 users of a UK cancer genetics service together with data derived from clinical consultations, we consider the way such patients or clients make sense of a cancer genetic risk estimate and how they integrate genetic risk information into their lifeworld. In particular, we note that patient-clients who are 'at risk' tend to see themselves in a liminal position betwixt the healthy and the sick, and that such individuals consequently seek recourse to systems of medical surveillance that can continuously monitor their state of health. Our analysis also revealed the fact that many of those deemed by professionals to be at low risk of inheriting cancer-related mutations subsequently strove to be re-categorised as being at moderate or high risk of an adverse outcome. A number of explanations concerning lay health beliefs, lay 'representations' of health and the nature of the patient-client's lifeworld are examined and assessed in order to account for this apparent paradox.

Attitude to Health↗