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PubMed2001

Native American cancer education: genetic and cultural issues.

BACKGROUND: The authors met with intertribal groups to learn about cultural issues related to cancer genetics. The information gathered from these meetings identified issues that are incorporated into the Genetic Education for Native Americans (GENA) interactive, innovative and multidisciplinary curriculum. METHODS: To address the diverse cultural and scientific issues, the faculty presented customized workshops during conferences for Native American college students. RESULTS: The authors discuss current issues and techniques in cancer education in Native American communities. CONCLUSIONS: Better understanding of tribal culture among researchers will enhance Native Americans' collaboration in research.

Cultural Characteristics↗
PubMedDate not supplied

Androgen receptor gene mutations do not occur in ovarian cancer.

Genetic alterations have been frequently found in ovarian cancer. There is some indirect evidence indicating that mutation of the steroid receptor genes may play a role in the carcinogenesis of ovarian cancer. Human androgen receptor (hAR) gene mutations have been found in up to 50% of hormone-relapsed prostate cancer. The role of hAR mutation and its association with decreased expression in ovarian cancer has never been elucidated. In this study mutations of hAR gene in 38 human ovarian cancer cell lines with different AR expression pattern were studied using SSCP. No mutation of the hAR gene was found. Mutation of hAR gene is an infrequent event and therefore unlikely to be involved in the development of ovarian cancer. The decreased expression of hAR in advanced ovarian tumor is not due to genetic aberration of hAR. Mutation screening of hAR may not provide any information for risk assessment of developing ovarian cancer.

Cystadenocarcinoma, Serous↗
PubMed1997

Ethical issues in genetic screening for cancer.

Genetically-based diseases with a late onset, such as BRCA1-dependent breast cancer or Huntington's disease, can be predicted by the screening of relevant mutations in members of high-risk families. Genetic screening is characterized by a conflict between respect for autonomy--e.g., the 'right not to know'--and responsibility toward future generations (the 'duty to know' for the sake of one's descendants). Other ethical conflicts are related to uncertainty as to benefits deriving from screening for mutations, since for most conditions no clearly effective therapeutical strategy has as yet been defined. In addition to monogenic high-penetrance conditions, polygenic low-penetrance susceptibility is attracting increasing attention, in particular with respect to environmental-genetic interactions (metabolic polymorphisms). A simple approach to genetic screening would be to weigh the benefits and costs of genetic screening against those of primary prevention, and a superficial conclusion might be that genetic screening is less expensive and, overall, more practicable than restriction of toxic exposures or other known risk factors for the disease. Economic advantage notwithstanding, however, giving precedence to screening over primary prevention would be unacceptable. A serious hazard of genetic screening is the implicit limitation of research efforts aimed at primary prevention, and a serious drawback is its potential application for selection of nonsusceptible employees. The principle of equity is easily violated by genetic screening of workers in view of the fact that genetically-based metabolic polymorphisms are distributed unevenly among different ethnic groups.

Beneficence↗
PubMedDate not supplied

Genetically linked cancers: prevention, detection, and treatment.

Although they are influenced by genetics, most human cancers are not inherited. However, genetic changes in cells are now believed to be the primary initiating factors that lead to cancer development. Although scientists have an increasingly better understanding of the relationship between genetics and cancer, nurses are not as well informed. There is now great potential to improve early detection and treatment of cancer; morbidity and mortality also will decrease as a result. However, this newly gained knowledge is not without its problems. Ethical dilemmas for both society and individuals are likely to arise. Becoming well-informed individuals will help to prepare nurses for cancer care in the future.

Cocarcinogenesis↗
PubMed1996

Frequent allele loss on 9p21-22 defines a smallest common region in the vicinity of the CDKN2 gene in sporadic breast cancer.

Genetic studies of chromosome arm 9p have indicated the presence of one or more tumor suppressor genes involved in genetic susceptibility to various types of human cancers. To define the extent of the specific deletion of 9p21-22 in human breast cancer, we have analyzed loss of heterozygosity and homozygous deletion of 9p21-22 in 68 paired blood and tumor samples by using fluorescent multiplex polymerase chain reaction (PCR). Of these tumors, 43% (29/68), including two ductal carcinomas in situ (DCIS), showed allele loss at one or more loci analyzed. Homozygous deletion for 9p markers was detected in 7/68 (10%) of tumor samples. Eleven tumors showed allele loss at all informative loci, and 18 tumors showed selective deletion on 9p21-22. Allele deletions in six tumors did not involve microsatellite markers flanking CDKN2. The smallest common region of deletion could be defined between D9S171 and D9S126. No significant associations were observed between deletion of 9p21-22 and any of the histopathological parameters analyzed. However, the abundance of deletions of this chromosomal region still suggests that loss and inactivation of putative tumor suppressor gene(s) located on 9p21-22 may be involved in the pathogenesis of breast cancer.

Alleles↗
PubMed2003

The genetics of pancreatic cancer.

The genetic basis for invasive and preoneoplastic neoplasms of the exocrine and endocrine pancreas has been the subject of a number of investigations in recent years. The purpose of this paper was to briefly review and summarize the pertinent findings. High frequency changes associated with pancreatic adenocarcinomas include mutations of the k-ras oncogene, and inactivating alterations of the p53, p16, and DPC4 tumor suppressor genes. Hereditary syndromes that have a known predisposition for pancreatic adenocarcinoma development include hereditary pancreatitis, familial atypical multiple mole melanoma (FAMM) syndrome, Peutz-Jeghers syndrome, familial breast cancer (BRCA-2), hereditary nonpolyposis colorectal cancer syndrome (HNPCC), and Li-Fraumeni syndrome. The underlying genetic defects have been identified and are currently being studied. Germline mutations of the men-1 gene are responsible for the MEN-1 syndrome, known to be associated with pancreatic endocrine tumors. It appears that somatic mutations of the gene are present in at least a subset of sporadic tumors. In addition, alterations in the Rb/p16 pathway appear to be commonly associated with pancreatic endocrine tumors. Further characterization of pancreatic tumors will result in a better understanding of the cellular pathways involved in pancreatic tumorigenesis and holds promise to identify targets for novel diagnostic and therapeutic strategies.

Adenocarcinoma↗
PubMed2000

Molecular genetics of cancer susceptibility.

Studies on the role of genetically polymorphic enzymes like cytochrome P450 1A1, arylamine N-acetyltransferase 2 or glutathione S-transferase M1 as cancer susceptibility factors date back more than 20 years, and some associations have been confirmed in several studies and meta-analyses. Overall, the extent of risk modulation due to these polymorphisms is only moderate but remains epidemiologically relevant. The role of some of these polymorphisms in human health may even be ambiguous: rapid acetylation, for example, protects from urinary bladder cancer but appears to increase the risk of laryngeal, lung and colon cancer. The first genetic polymorphisms in xenobiotics transporters such as P-gp (MDR1) and MRP2 have recently been identified. These polymorphisms may have great impact as cancer susceptibility factors as well as factors modulating the outcome of cancer treatment. Enzymes involved in generation or detoxification of reactive oxygen species also have to be considered; one of these enzymes, myeloperoxidase, constitutes a relatively strong lung cancer risk factor, as confirmed in 4 independent studies. Other genes, including those coding for DNA repair enzymes, signal transduction and cell growth regulation, may ultimately prove more important than the metabolic enzymes as cancer susceptibility factors. Study designs in molecular genetic epidemiology are evolving; large ongoing prospective trials increasingly allow confirmatory nested case control studies to be performed. However, carefully controlled, large case-control studies will remain the mainstay in molecular genetic epidemiology. Molecular genetic epidemiological evaluation of response to chemoprevention as well as response to the adverse events of cancer chemotherapy are likely to provide results that may be useful for individualized prevention and treatment in the near future. Since routine genotyping of all persons is now feasible, something like a genotype passport may soon become reality, and molecular and clinical epidemiological studies will have to provide the basis for understanding how to use genotype data for the benefit of the population.

Animals↗
PubMed2004

Frequent amplification and overexpression of CCND1 in male breast cancer.

Genetic events underlying the pathogenesis of breast cancer have been studied extensively and several clinically significant markers have been identified. For example, amplification and overexpression of the ERBB2 oncogene is associated with poor prognosis in breast cancer and ERBB2 serves as a target for antibody-based therapy. Current knowledge on the pathogenesis of male breast cancer (MBC) is limited. The purpose of our study was to investigate the potential relevance of a series of genes known to be amplified in female breast cancer (FBC) in a the development and pathogenesis of MBC. To this end, we applied fluorescence in situ hybridization and immunohistochemistry to the analysis of 128 breast tumors from males. Amplification of ERBB2, MYC, PPM1D and ZNF217 was detected rarely (1-2% of tumors) indicating a considerably lower amplification frequency than in FBC. CCND1 amplification was observed in 12% of cases, being in good concordance with findings from FBC. In addition, CCND1 overexpression was detected in 63% of tumors and was associated with ER positivity (p < 0.0001). Our results indicate distinct differences in the genetic basis of MBC and FBC and suggest that marked differences exist in the pathogenesis of these diseases. The lack of ERBB2 involvement was especially unexpected and implies that ERBB2-targeted therapies are unlikely to be beneficial in MBC. Furthermore, the high frequency of hormone receptor positivity and the association between ER positivity and CCND1 overexpression supports the notion that hormonal regulation is likely to be essential for the development of MBC.

Breast Neoplasms, Male↗
PubMed2000

Ras activation in human breast cancer.

Genetic ras mutations are infrequent in breast cancer but Ras may be pathologically activated in breast cancer by overexpression of growth factor receptors which signal through Ras. Using a highly sensitive, coupled enzymatic assay, we measured Ras activation in 20 breast cancers, two fibroadenomas, and seven normal breast samples. Ras was highly activated compared to benign tissue in 11 of the 20 cancers; 7 of these 11 cancers expressed both the epidermal growth factor (EGF) and ErbB-2/neu/HER-2 receptors with the remaining four cancers with high Ras activation expressing one of these two receptors. In the other nine cancers, Ras activation was similar to that observed in benign breast tissue with none of these cancers expressing the EGF receptor while one expressed the ErbB-2 receptor. None of the cancers tested had an activating K-ras mutation nor did any of the cancers express a truncated EGF receptor or the c-FMS receptor. The activity of mitogen-activated protein (MAP) kinase was high in the cancers, and reflected the degree of Ras activation. In cultured mammary tumor cell lines, we showed that Ras activation was ligand dependent in cells overexpressing the ErbB-2 receptor. Thus, Ras was abnormally activated in breast cancers overexpressing the EGF and/or ErbB-2 receptors indicating there are sufficient ligands in vivo to activate these receptors, and this work provides a basis for new target-based treatments of this disease.

Breast Neoplasms↗
PubMed2000

Genetic testing.

New research developments in the molecular genetics of cancer have led to the feasibility of cancer genetic testing. At present, genetic test results can better inform individuals at risk about appropriately tailored strategies for cancer screening and prevention. In the future, more persons will be eligible for genetic evaluation; in particular, if it is shown that patients with cancer who are carriers of germline mutations respond differently to treatments, genetic testing may be warranted. Consideration needs to be given to the appropriate delivery of genetic risk assessment and testing. There is a great potential for misinterpretation of gene test results and for adverse psychosocial consequences for patients. Genetic counseling is an important component in cancer risk assessment and management, particularly in helping persons at risk understand the implications of gene test results in the context of their experience with cancer and surveillance.

Confidentiality↗
PubMed2002

Interest in genetic prostate cancer susceptibility testing among african American men.

Six regions for prostate cancer genes have been identified, and it is anticipated that prostate cancer susceptibility testing will be available in the future. This correlational study identified predictors for interest in prostate cancer susceptibility testing among African American men. Participants were 320 African American men from the African American Hereditary Prostate Cancer Study and the South Carolina Prostate Cancer Education and Screening Study participated. Two questions measured interest in genetic prostate cancer susceptibility testing and family history of prostate cancer. Chi-square analyses by family history as well as demographics (age, education, marital status) were performed. Most of the men (277 [87%]) indicated an interest in genetic prostate cancer susceptibility testing. Interest in undergoing testing did not vary by family history, age, or education. Marital status was the only significant demographic predictor. Men who were married were significantly more likely to respond with a "yes" to interest in prostate cancer susceptibility testing than were men who were not married. The high "yes" response rate and the men's confusion between the genetic prostate cancer susceptibility testing and prostate cancer screening highlight the need for public education once prostate cancer genes are identified and available for public testing.

Adult↗
PubMed2000

Molecular biology of breast cancer metastasis. Genetic regulation of human breast carcinoma metastasis.

The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention.

Antigens, CD↗
PubMed1998

Overview of cancer and genetics: implications for nurse practitioners.

The understanding of cancer at a molecular level and of the contribution of certain genetic mutations to the development of cancer is progressing at an unparalleled rate. Advances in technology and discoveries stemming from the Human Genome Project now provide the means to test individuals for the presence of mutations associated with some known hereditary cancer syndromes. Although many ethical, legal, and psychosocial issues associated with testing remain unresolved, predisposition genetic testing is having and will continue to have a significant impact on health care. Nurse practitioners will play a vital role in assessing clients for increased risk of developing cancer, educating clients about the availability of testing, making referrals for cancer genetic counseling and risk assessment, and providing follow-up care in the community for patients found to be at increased risk.

Genetic Testing↗
PubMed2006

Genetic and epigenetic analysis of von Hippel-Lindau (VHL) gene alterations and relationship with clinical variables in sporadic renal cancer.

Genetic and epigenetic changes in the von Hippel-Lindau (VHL) tumor suppressor gene are common in sporadic conventional renal cell carcinoma (cRCC). Further insight into the clinical significance of these changes may lead to increased biological understanding and identification of subgroups of patients differing prognostically or who may benefit from specific targeted treatments. We have comprehensively examined the VHL status in tissue samples from 115 patients undergoing nephrectomy, including 96 with sporadic cRCC. In patients with cRCC, loss of heterozygosity was found in 78.4%, mutation in 71%, and promoter methylation in 20.4% of samples. Multiplex ligation-dependent probe amplification identified intragenic copy number changes in several samples including two which were otherwise thought to be VHL-noninvolved. Overall, evidence of biallelic inactivation was found in 74.2% of patients with cRCC. Many of the mutations were novel and approximately two-thirds were potentially truncating. Examination of these and other published findings confirmed mutation hotspots affecting codons 117 and 164, and revealed a common region of mutation in codons 60 to 78. Gender-specific differences in methylation and mutation were seen, although not quite achieving statistical significance (P = 0.068 and 0.11), and a possible association between methylation and polymorphism was identified. No significant differences were seen between VHL subgroups with regard to clinicopathologic features including stage, grade, tumor size, cancer-free and overall survival, with the exception of a significant association between loss of heterozygosity and grade, although a possible trend for survival differences based on mutation location was apparent.

Adult↗
PubMed1998

Microsatellite instability in young patients with colorectal cancer.

Genetic instability is closely correlated to the pathogenesis of hereditary non-polyposis colon cancer (HNPCC), which is clinically characterized by a family history and early onset. To investigate the role of genetic instability in young patients with colorectal cancer (CRC), 22 CRC patients, who were aged younger than 30 at the time of diagnosis, were studied. Patients with familial adenomatous polyposis were excluded. Among the 22 cases, seven were identified as microsatellite instability positive (MI+), and more than five microsatellite markers among the 15 tested markers showed an additional band pattern in the tumor tissue. None of the remaining 15 cases showed instability in any microsatellite marker. Two of seven MI+ cases were classic HNPCC. While all MI+ cases had one or no metastatic lymph node, 53.3% of MI- cases showed metastasis in two or more regional lymph nodes. Allelic deletion of the 17p12-13 chromosome around the p53 locus occurred in 16.7% of MI+ cases, and 80.0% of MI- cases showed loss of heterozygosity at that locus. hMSH2 Protein expression, assessed by immunohistochemistry, was absent in two cases, both of which were MI+. When we tested two to four sites of MI+ tumors, transforming growth factor beta receptor type II was mutated in a homogeneous pattern in five MI+ cases. In addition, frame-shift mutations of BAX, insulin-like growth factor II receptor, hMSH3 and hMSH6 were found in three cases, five cases, five cases and one case, respectively. In contrast to the consistent mutation of the transforming growth factor-beta receptor type II gene, mutations of other genes varied in different portions of the tumors.

Adenocarcinoma, Mucinous↗
PubMed2004

Novel regions of amplification on 8q distinct from the MYC locus and frequently altered in oral dysplasia and cancer.

Genetic studies aimed at identifying key alterations in oral cancers have focused on analysis of tumors, with few such studies using early oral premalignant lesions (OPLs) because of limitations in both sample availability and size. In this study, we used a randomly amplified polymorphic DNA (RAPD)-PCR approach to fingerprint DNA from microdissected normal and dysplastic cells and identified two recurrent genetic alterations on the long arm of chromosome 8 in OPLs, one mapping to 8q22 and the other to 8q24 near the MYC locus. We constructed a high-resolution bacterial artificial chromosome (BAC) comparative genomic hybridization array consisting of 166 overlapping BAC clones that spans about 52 Mbp, from 8q21 to 8q24. Hybridization of DNA from microdissected oral tumors to the array revealed alteration at 8q24, with amplification of the BAC containing MYC. Strikingly, at least two other novel regions of amplification at 8q22 were identified. Microsatellite analysis of 93 oral dysplasias and tumors confirmed the presence of one of the alterations at 8q22. Loss of heterozygosity (LOH) at D8S1830, mapping within one of the regions of amplification, was observed in high frequency in both OPLs and tumors. Of the 37 cases with LOH at D8S1830, 23 (62%) showed retention at D8S1793, which maps 1.6 Mbp centromeric to MYC. This is further support for the alteration at 8q22 being distinct from MYC. These data raise the possibility of additional oncogenes on 8q near the MYC locus that are potentially involved in OPL disease progression.

Biomarkers, Tumor↗
PubMed2004

Women's satisfaction with genetic counseling for hereditary breast-ovarian cancer: psychological aspects.

Women who participate in BRCA1/2 cancer genetic counseling do so for a variety of reasons, including learning quantitative risk information about their chances of developing hereditary breast-ovarian cancer at some point during their lifetimes. For these women, obtaining pre-test and disclosure genetic counseling with a professional affords them numerous potential benefits, including adequate preparation for, and accurate interpretation of, their test results. In consequence, women commonly report being highly satisfied with their cancer genetic counseling experience, even if the information learned through testing suggests they are at increased cancer risk. This occurrence raises an interesting question, namely, what are the psychological aspects of satisfaction with genetic counseling for hereditary breast-ovarian cancer in women? To answer this question, we administered the Genetic Counseling Satisfaction Scale (GCSS) to a convenience sample of 61 women participating in BRCA1/2 pretest genetic counseling, and re-administered the GCSS to approximately one-third of these women at disclosure. Available psychological data included personality, distress, and family functioning. In bivariate analyses, optimism and family functioning were positively associated with pretest satisfaction. With respect to satisfaction at disclosure, general and cancer-specific distress were negatively associated with satisfaction. Our findings suggest that psychological aspects of satisfaction with cancer genetic counseling vary, with individual differences and family functioning playing a role at pretest, and distress playing a role at disclosure. The implications for future research and clinical practice are discussed.

Adult↗
PubMed2003

Information-seeking behaviour and psycho-social interactions during the genetic testing process.

OBJECTIVES: The first aim of this study was to investigate the information-seeking behaviour (ISB) of women attending cancer genetic consultations at which the possibility of BRCA testing is considered. We focused here specifically on ISB apart from the cancer genetic consultation, i.e. on what complementary sources of information about genetic testing were consulted and what factors were involved in this behaviour. The second aim was to study the role of the social network used by the patients to collect various opinions on which to base their decisions about being tested. METHODS: A prospective cohort study (2000-2002) was therefore carried out on all women attending a single cancer genetic clinic in France after a BRCA1/2 analysis had been proposed. Closed questionnaires were administered before and after the second cancer genetic consultation. The purpose of this consultation was to confirm the patient's decision to be tested. RESULTS: Results were analysed in 108 subjects (mean age 47 years, SD 11 years; 74% affected by breast/ovarian cancer). Prior to the 2nd consultation, 35.2% of the women had actively looked for information about BRCA1/2 testing, as compared to 25.0% afterwards. After multivariate adjustment by logistic regression, the pre-consultation ISB was found to be associated with greater satisfaction with the information about the psycho-social consequences of genetic testing [adjusted odds ratio (ORadj) 1.03, 95% confidence interval (CI) 1.01-1.06] (scale from 0 to 100) and about the certainty of being a gene carrier (ORadj 3.04, 95% CI 1.16-7.98). Those who actively looked for complementary information were also more often accompanied at the consultation by a family member (ORadj 4.82, 95% CI 1.85-12.56). The other variables tested (depression, coping, socio-demographic and medical characteristics) were not significant (p > 0.05). The role of the social network in the decision making process was perceived as being less helpful when the persons consulted tended to have neutral or unfavourable opinions about genetic testing. CONCLUSIONS: Few women actively sought complementary information about BRCA genetic testing in addition to the cancer genetic consultation. Those who did so differed from the others in terms of their social network and their satisfaction with the consultation. The cancer geneticist is the key actor in women's decision making about genetic testing.

Attitude to Health↗