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At least 667 records · Page 37Linked to original sources
PubMed2006

APC I1307K and the risk of prostate cancer.

The kin-cohort design has been proposed as an alternative to traditional case-control and cohort measures to evaluate inherited susceptibility to cancer in population-based studies. Here, we used this design to evaluate inherited susceptibility to prostate cancer associated with APC I1307K using data from the Molecular Epidemiology of Colorectal Cancer study. Two techniques were used to compare the incidence of prostate cancer in APC I1307K carriers. First, we compared the incidence of prostate cancer in relatives of mutation carriers and noncarriers using standard techniques for survival analysis. Second, we used the marginal maximum likelihood method for kin-cohort analysis to infer the genotypes in the relatives. We also evaluated APC I1307K in 75 Ashkenazi Jewish individuals with prostate cancer from 27 families enrolled in the University of Michigan Prostate Cancer Genetic Study. We observed a slightly increased risk of prostate cancer in relatives of APC I1307K carriers, however, this difference was not statistically significant (hazard ratio, 1.6; 95% confidence intervals, 0.7-3.4). Similar conclusions were drawn using both techniques for kin-cohort analysis. APC I1307K was found in 7.4% of families genotyped, which is slightly higher than the allele prevalence reported in Ashkenazi Jews in the general population. In addition, we did not observe loss of heterozygosity at APC or a somatic mutation near APC I1307K using microdissected tumor DNA from mutation carriers enrolled in the Prostate Cancer Genetic Study. Overall, the evidence for an association between APC I1307K and prostate cancer is not compelling. APC I1307K is unlikely to play a clinically meaningful role in susceptibility to prostate cancer.

Age Distribution↗
PubMed2000

[Hereditary cancer and genetic testing: the role of division of clinical and molecular genetics].

Genetic testing has been widely available and useful in several kinds of familial cancer. Shinshu University Hospital established a division of clinical and molecular genetics as one of its central service departments. We have a staff meeting once a week to discuss each case to provide the suitable counseling and the ethical-legal and social issues. We performed genetic testing in 44 cases, including familial adenomatous polyposis, multiple endocrine neoplasia type 1 and 2, familial breast cancer, von Hippel-Lindau disease, and Li-Fraumeni syndrome. This is the first clinical genetics department in the National University Hospitals in Japan and this system increases the utility of genetic testing.

Ethics↗
PubMed1996

[Ataxia telangiectasia and genetic predisposition to cancer].

Ataxia telangiectasia (AT) is a genetic disorder with an autosomic recessive transmission. Occurring during childhood, it affects different organs and/or systems. Physiopathology is still unclear. The first clinical signs are evident early in childhood and evolution always leads to death. The secondary cause of mortality in 10 to 15% of the affected is the development of cancers. Genetic predisposition to cancer for homozygotes, as well as for heterozygotes, is one of the most remarkable aspects of this disease. For heterozygotes the risk of cancer is three times that of the norm. The gene responsible for the disease has been cloned. Its function may resolve some questions, and provide the link between degenerative process, cancer susceptibility and immunodeficiency evident in AT patients.

Ataxia Telangiectasia↗
PubMed2002

The genetics of ovarian cancer.

A family history of ovarian cancer confers an increased risk of ovarian cancer. We review the literature quantifying the familial risks associated with ovarian cancer and assess the evidence that the familial clustering of ovarian cancer is genetically determined. We then describe the known high-penetrance genes, the ovarian cancer risks attached to them and their contribution to ovarian cancer in families and in the general population. The evidence for the existence of other ovarian cancer genes is then considered.

Female↗
PubMed2002

Cytogenetics and molecular genetics of cancer of the prostate.

Prostate cancer remains the most common male malignancy in Western countries and the second-leading cause of death from cancer in males. Progress in the understanding of molecular and genetic mechanisms leading to this disease has only recently begun to offer a glimpse of the genes, chromosomal sites, and proteins implicated in the development and progression of prostate tumors. This brief review addresses some of the key issues in prostate cancer research, including a discussion of both hereditary and sporadic cancers as well as specific genes and chromosomal loci that likely play a part in the etiology of this disease.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

Microsatellite instability in multiple colorectal tumors.

Tumor multiplicity is a hallmark of hereditary cancers: in the colon-rectum multiple tumors represent 5-10% of all colorectal cancer cases. A portion of these cases belongs to hereditary non-polyposis colorectal cancer (HNPCC), a genetic cancer syndrome due to mismatch repair (MMR) gene mutations, phenotypically expressed as microsatellite instability (MSI); the majority of multiple tumors, however, is apparently without any family history. We analyzed 78 (38 synchronous and 40 metachronous) neoplasms from 37 patients with multiple tumors of the large bowel, both HNPCC and sporadic, with the aim of identifying a common genetic basis in multiple tumors. DNA was extracted from normal and cancerous formalin-fixed tissue and was analyzed for MSI using 6 markers. Tumors showing MSI in at least 2 of 6 microsatellite loci were defined as MSI(+). The overall number of MSI(+) tumors was 22 (28.2% of the total). A significant difference in the rate of MSI(+) between HNPCC and sporadic tumors was observed (85% vs. 17%). In the same patients, the MSI phenotype of synchronous tumors (both HNPCC and sporadic) tended to be more concordant than that of the metachronous ones. The higher frequency of MSI in HNPCC than in sporadic tumors, even when multiple, suggests that the involvement of MMR genes in the pathogenesis of the sporadic cases may be uncommon, thus confirming that screening for MSI in multiple colorectal tumors could be a useful tool in the identification of HNPCC in the general population.

Colorectal Neoplasms↗
PubMedDate not supplied

How aneuploidy may cause cancer and genetic instability.

It has been difficult to find a common cause for the many and complex phenotypes of cancer such as dedifferentiation, invasiveness, abnormal morphology, growth rate and metabolism, genetic instability, progression to malignancy, cellular heterogeneity of phenotypes and karyotypes, and clonal origin despite heterogeneity. Over 100 years ago aneuploidy, an abnormal balance of chromosomes, was proposed to cause cancer. However, the aneuploidy hypothesis has since been abandoned, in favor of the gene mutation hypothesis, because it could not offer conventional explanations for cancer-specific phenotypes. For example, the aneuploidy hypothesis seemed unable to (i) explain the genesis of abnormal, cancer-specific phenotypes, (ii) reconcile the heterogeneous karyotypes with the clonal origin of cancers, (iii) explain aneuploidy in non-cancerous cells, and (iv) explain how carcinogens would cause aneuploidy. Here we introduce new evidence that aneuploidy offers a simple, coherent explanation of all cancer-specific phenotypes: (i) Congenital and experimental aneuploidy is now known to generate abnormal phenotypes, such as Down syndrome in humans and cancer in animals. (ii) Based on metabolic control analysis, we have derived equations that correlate degrees of aneuploidy with the resulting phenotype abnormalities. These equations suggest that aneuploidy must exceed a certain threshold to generate cancer-specific phenotypes. Therefore, we propose that multistep carcinogenesis corresponds to multiple steps of aneuploidization. (iii) Aneuploidy is also sufficient to explain cancer-specific, karyotypic instability. Since aneuploidy imbalances the highly balance-sensitive components of the spindle apparatus it destabilizes symmetrical chromosome segregation. This autocatalytic instability is the reason why cancers have heterogeneous karyotypes, but are clonal for aneuploidy. Progression to malignancy corresponds to selection of ever more aggressive karyotypic variants. (iv) Both non-genotoxic and genotoxic carcinogens can cause aneuploidy by physical or chemical interaction with mitosis proteins. We conclude that aneuploidy offers a mechanism of phenotype alteration which--above a certain threshold--is sufficient to cause all cancer-specific phenotypes, and is independent of gene mutation.

Aneuploidy↗
PubMed1989

Molecular genetic studies of colon cancer.

Molecular genetic studies of tumor-specific allele loss, originally associated primarily with research regarding childhood hereditary cancers such as retinoblastoma and Wilms' tumors, only lately have been recognized as a relatively fast and fruitful way of locating cancer genes on human chromosomes. To date, over 25 different cancers have been tied to a gene (or genes) on a specific chromosome when this method has been used. During the past year alone, this approach has permitted detection of three genes involved in either hereditary or sporadic colorectal cancers. These three genes, located on chromosomes 5q, 17p, and 18q, are believed to belong to the newly described tumor suppressor (or growth suppressor) gene class, whose effects are opposite those of activated cellular oncogenes, which promote uncontrolled cell growth. Present studies, however, have not shown losses of any of these tumor suppressor genes to be correlated with the presence of activated ras genes in colorectal adenomas or carcinomas. During progression from adenoma to carcinoma, ras gene mutations and 5q allelic deletions are likely to be earlier events, whereas allelic losses from chromosomes 18q and 17p seem to occur more often in advanced tumors. Involvement of the genes on 5q (FAP) and 18q (Lynch syndrome II) in hereditary colon cancer syndromes is supported by linkage studies, but their respective roles (as well as that of the gene on 17p) in familial and sporadic colorectal cancer remain to be precisely defined. Probable isolation of these three genes by molecular cloning within the next few years will help elucidate their specific biologic functions. It will also permit early detection, and thus prevention, of some familial colon cancers (such as FAP), and possibly allow DNA marker-based separation of different colon cancer subtypes of similar histologic appearance.

Adenoma↗
PubMed2003

Colon cancer and genetic variation in folate metabolism: the clinical bottom line.

So far, evidence for the relation between folate intake and colorectal cancer has been insufficient to lead to specific public health interventions. In principle, data on the relation between genetic variation in folate metabolism and colorectal neoplasia could be used to corroborate the data on the relation between folate intake or status and the disease, strengthening the evidence base for primary prevention. Issues in considering the relation between a health outcome and genetic variation in metabolism of nutrients or other food components include knowledge of gene function, linkage disequilibrium, population stratification, study size and quality, and gene-environment interaction. Overall homozygosity for MTHFR variant genotypes is associated with a reduced risk of colorectal cancer, the opposite of what might have been expected a priori. This has led investigators to place greater emphasis on the functions of folate and methylenetetrahydrofolate reductase in DNA synthesis. Folate and related nutrients may be important after adenoma formation. A challenge for the future is to characterize the effects of multiple genes influencing folate metabolism. Limited data for colorectal cancer suggest that the effect of a low folate diet overrides the effect of genotype, but two studies of adenomas suggested the opposite. Another potential role of information on genetic variation in folate metabolism is in the management of colorectal cancer but most studies have been small, have included selected patient groups, and have made limited adjustment for potentially important factors.

Adenoma↗
PubMed2006

Genetic basis of cancer of the kidney.

Kidney cancer is not a single disease. It is made up of a number of different types of cancer that occur in the kidney, each with a different histologic type, having a different clinical course, responding differently to therapy and caused by a different gene. The identification of families with a predisposition to the development of renal neoplasms, including von Hippel-Lindau (VHL), hereditary papillary renal carcinoma (HPRC), Birt-Hogg-Dubé (BHD), and hereditary leiomyomatosis and renal cell cancer (HLRCC), has made possible the identification of the different genes for these cancers. The genetic basis for each of these has been identified with current investigation focusing on the mechanisms of carcinogenesis. The elucidation of molecular pathogenesis in these familial forms of kidney cancer should provide the opportunity to determine successful approaches for novel therapeutic agents.

Carcinoma, Papillary↗
PubMed2005

Impact of direct-to-consumer advertising for hereditary breast cancer testing on genetic services at a managed care organization: a naturally-occurring experiment.

PURPOSE: To describe the impact of Myriad Genetics, Inc.'s direct-to-consumer advertising (DTC-ad) campaign on cancer genetic services within two Managed Care Organizations, Kaiser Permanente Colorado (KPCO), Denver, Colorado, where the ad campaign occurred, and Henry Ford Health System (HFHS), Detroit, Michigan, where there were no advertisements. METHODS: The main outcome measures were the changes in number and pretest mutation probability of referrals approved for cancer genetic services at KPCO and HFHS during the campaign versus the year prior, and mutation probability of those undergoing testing. RESULTS: At KPCO, referrals increased 244% during the DTC-ad compared to the same time period a year earlier (P value<0.001). The proportion of referrals at high pretest probability of a mutation (10% or greater) dropped from 69% the previous year to 48% during the campaign (P value<0.001). There was no significant change in pretest mutation probability among women who underwent testing between the two time periods. HFHS reported no significant change between the two time periods for numbers or mutation probability of referrals, or for mutation probability of women tested. CONCLUSION: The DTC-ad caused significant increase in demand for cancer genetic services. In the face of potential future DTC-ad for inherited cancer risk, providers and payers need to consider the delivery of genetic services and genetic education for persons of all risk levels.

Adult↗
PubMed1994

Genetic susceptibility to lung cancer with special emphasis on CYP1A1 and GSTM1: a study on host factors in relation to age at onset, gender and histological cancer types.

Genetically based differences in metabolism, related to MspI restriction site and Ile-Val polymorphisms of the cytochrome P450 (CYP) 1A1 gene and the null genotype of glutathione transferase class mu (GSTM1), have been reported to be associated with lung cancer susceptibility. The present study was set up to establish the frequencies of the polymorphic genotypes of CYP1A1 and GSTM1 in Sweden, to evaluate a possible increased incidence of the genotypes associated with higher lung cancer risks among Swedish lung cancer patients and to try to make a combined risk estimate for carriers of multiple risk alleles. In a healthy control group, all under 66 years of age, 53% (174/329) of the subjects were of the GSTM1(-) genotype, while in a hospital control group 49% (39/79) carried the GSTM1(-) genotype. In the investigated lung cancer patients this genotype was found in 56% (165/296) and among those patients diagnosed before 66 years of age the deficient genotype was found in 60% (78/131). The highest proportion of the GSTM1(-) genotype was found in patients diagnosed with adenocarcinoma (63%, 29/46) and small cell carcinoma (72%, 21/29) before 66 years of age and among female squamous cell carcinoma patients (79%, 15/19). The allelic variants in CYP1A1 were equally distributed in lung cancer patients and controls. The m1/m2 and m2/m2 genotypes of the MspI site and the Ile/Val genotype were, however, slightly over-represented in squamous cell carcinoma patients. Among patients with squamous cell carcinoma diagnosed before 66 years of age the m1/m2 genotype was found in 28% (10/36), whereas the same genotype was observed in 16% (52/329) of healthy control subjects. A combined risk of squamous cell carcinoma was indicated for patients, diagnosed before 66 years of age, carrying both GSTM1(-) and m2 alleles (OR = 3.0, 95% CI = 1.2-7.2).

Adenocarcinoma↗
PubMed1999

Cancer and genetics: what we need to know now.

Profound changes brought about by discoveries in molecular biology may enable us in the future to treat cancer without causing late effects or to prevent cancer altogether. Even before that happens, the age of molecular medicine has arrived. Molecular biology is the study of biological processes at the level of the molecule. A major aspect of molecular biology is molecular genetics--the science that deals with DNA and RNA. Most of the progress in molecular biology has been made in the second half of the 20th century. Each discovery or technological innovation has built on previous discoveries and paved the way for the next, culminating in the current effort to map, sequence, and understand the functions of the entire human genome. In the past 20 years, many pieces of the cancer puzzle have been found, showing us how the normal cellular control mechanisms go awry to cause cancer and setting the stage for genetic testing and disease treatment. These new discoveries bring both promise and peril. To provide comprehensive care for survivors of childhood cancer and care in other settings as well, health care providers must now be familiar with the concepts and language of molecular biology, understand its applications to cancer care, and be fully informed about its implications for clinical practice, research, and education.

Child↗
PubMed1996

Emotional and behavioral responses to genetic testing for susceptibility to cancer.

As genetic testing for susceptibility to cancer becomes more widely available, cancer-care providers will become more involved in counseling patients about cancer risks and the meaning of genetic test results. As a result, oncologists and oncology nurses need to be aware of the unique psychological issues and challenges posed by genetic testing for cancer susceptibility. This paper first describes a psychological profile of individuals who are likely to opt for such testing, based on extrapolation from studies of people at high risk of cancer. It also discusses the possible adverse emotional responses individuals may have to learning test results, and offers suggestions for preventing or lessening these psychological consequences. In addition, the article explores a wide range of issues relating to the genetic counseling process and the impact of genetic information on family relationships.

Adaptation, Psychological↗
PubMed1996

Parental cancer and genetic predisposition in malignant pleural mesothelioma: a case-control study.

Familial clustering of pleural mesothelioma (PM) has been previously reported suggesting that genetic factors (predisposition) may be involved in PM. We studied parental cancer history in a cohort of 39 cases of PM and 259 age matched controls to assess the possible influence of family history on PM risk. Cases consisted of 39 patients with PM treated at our institution between 1978 and 1993. An age frequency matched control group (by 5-year age groups) consisted of 259 subjects who were spouses or friends of patients undergoing resection of primary lung cancer. Data were obtained by interview of controls and interview of the patient or next of kin (usually spouse) for cases. The following data were obtained using a standard questionnaire and medical record review; age, sex, date of diagnosis, history of asbestos exposure, smoking history, method of diagnosis, histologic subtype, type of treatment, parental cancer history and tumor type. Cases and control frequency of parental cancer and site specific tumor frequency were compared using chi-square analysis. Twenty-eight (71%) cases reported a parental history of cancer versus 114 (44%) in the control group (P<0.01). Gastrointestinal malignancies were the predominant tumor type among parents of cases, i.e. 11 cases (40%) versus 25% of controls (P<0.01). No other tumor site showed an increased frequency among cases. These data suggest a possible role for family history in the development of PM. Genetic predisposition may be important in the etiology of this tumor.

Asbestos↗