Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cancer genetics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources

Psychosocial issues in cancer genetics--current status and future directions.

Diagnostic tests are now available that allow genetic testing for several types of cancer. The aim of genetic counseling and testing for cancer is to educate individuals about cancer risk and cancer prevention, which it is hoped will lead to a reduction in morbidity and mortality. However, at this relatively early stage in the development of genetic counseling and testing programs, information is needed on the psychosocial impact of such programs on both the individual counselee and his/her family. This paper reviews the findings obtained during the past decade on the uptake of genetic testing, reasons for undergoing genetic testing, and the impact of genetic counseling and testing on feelings of distress and guilt. Specific attention is paid to experiences with prophylactic mastectomy and oophorectomy and the effectiveness of the uptake of and satisfaction with these risk-reducing procedures. In addition, the possible impact of genetic testing on insurance, work and future plans is discussed. Suggestions are given for translating research findings into psychosocial services and future research efforts.

Attitude to Health↗

Cancer genetics knowledge and beliefs and receipt of results in Ashkenazi Jewish individuals receiving counseling for BRCA1/2 mutations.

BACKGROUND: Genetic counseling for BRCA1 and BRCA2 mutations (mutations associated with increased risk of breast-ovarian cancer) endeavors to communicate information that will help individuals make informed decisions regarding genetic testing. METHODS: This repeated-measures study examined cancer genetics knowledge and beliefs before and after counseling and their relationship to receipt of results for BRCA1/2 mutations in 120 highly educated Ashkenazi Jewish individuals. RESULTS: A repeated-measures analysis examined change in knowledge and beliefs regarding personal behavior, mechanisms of cancer inheritance, meaning of a positive result, practitioner knowledge, frequency of inherited cancer, and meaning of a negative result from pre- to post-counseling with the between subjects variables of education (with/without graduate training) and personal history of breast or ovarian cancer (yes/no), and risk of having a mutation entered as a covariate. Mechanisms of cancer inheritance, meaning of a positive result, and practitioner knowledge increased from pre- to post-counseling. Those with graduate training had higher ratings of mechanisms of cancer inheritance ratings and lower ratings of frequency of inherited cancers than those without. Mann-Whitney U tests found those testing had higher ratings in mechanisms of cancer inheritance, specifically in the association of multiple primary cancers with hereditary cancer, than those not testing. CONCLUSIONS: Genetic counseling is helpful in improving overall knowledge of cancer genetics even for highly educated individuals. Particular areas of knowledge improvement should be explored in relation to receipt of results, especially to further elucidate the relationship of knowledge of the association of multiple primary cancers with hereditary cancer to receipt of test results.

Adult↗

Apoptosis: a link between cancer genetics and chemotherapy.

Defects in apoptosis underpin both tumorigenesis and drug resistance, and because of these defects chemotherapy often fails. Understanding the molecular events that contribute to drug-induced apoptosis, and how tumors evade apoptotic death, provides a paradigm to explain the relationship between cancer genetics and treatment sensitivity and should enable a more rational approach to anticancer drug design and therapy.

Animals↗

Breast cancer, genetics, and age at first pregnancy.

Hereditary breast cancer shows a distinctive natural history characterised by an earlier age of onset, excess bilaterality, vertical transmission, heterogeneous tumour associations, and improved survival when compared to its sporadic counterpart. To date, very little attention has been given to interrelationships between breast cancer risk factors and genetics. In the general population, early age of first term pregnancy has been generally accepted as protective against breast cancer. In addition, recent findings suggest that an early age of first pregnancy may be associated with an earlier age of breast cancer diagnosis. We studied the age at first pregnancy and age at onset of breast cancer among 162 females at 50% genetic risk, 72 of whom had already developed the disease. We then compared them to 154 consecutively ascertained breast cancer patients from the Creighton Cancer Center. In the hereditary subset (1) early first term pregnancy did not alter the frequency of breast cancer; (2) early age at first term pregnancy was not associated with an earlier age at cancer diagnosis; and (3) age of breast cancer onset in nulliparous females was not significantly lower than that in females having at least one term pregnancy. We speculate, therefore, that in our hereditary population, pregnancy does not influence the natural history of breast cancer in the same way that it does in the population at large.

Adult↗

shRNA libraries and their use in cancer genetics.

RNA interference was originally described as a powerful tool to inhibit gene expression in model organisms. Until recently, loss-of-function genetic screens in mammalian cells were hampered by a lack of suitable tools that can be used in a high-throughput format. Here we discuss the construction of short-hairpin RNA (shRNA) vector libraries, in particular those generated at the Netherlands Cancer Institute (NKI), and their application in mammalian cancer genetics. We describe their virtues and limitations, as well as different options for screening such libraries.

Animals↗

Using cancer genetics to guide the selection of anticancer drug targets.

The genetic alterations that cause cancer are coming into view. Genes that are recurrently mutated in a particular form of human cancer flag the proteins (or molecular pathways) that are critical for the evolution of that malignancy. The first generation of anticancer agents prospectively guided by these principles, for which imatinib mesylate is a prototype, inhibit the biochemical activities that result from gain-of-function oncogenic mutations. Advances in somatic cell genetics and chemical biology should facilitate the development of a second generation of agents that will inhibit proteins that are selectively required for survival in the context of specific cancer-causing mutations, whether loss-of-function or gain-of-function.

Animals↗

Psychological issues in cancer genetics: current research and future priorities.

There has been a rapid expansion of genetics research in the field of cancer since cancer predisposing genes are now known to cause a proportion of common cancers as well as rarer cancer syndromes. As a result, the psychosocial impact of being at high risk of cancer has become a focus of evaluation, and studies are being reported which set out to evaluate both the uptake and psychological outcome of genetic counselling, testing and surveillance. Available data concerning psychological aspects are reviewed, including for example, possible implications of genetic testing, attitudes and uptake of breast screening and accuracy of women's risk estimates. Work is in progress to assess the more controversial areas of prophylactic mastectomy, and chemoprevention. Other research examines the longer term impact of belonging to a Cancer Family, and of interventions offered to high risk families. This is crucial since the uptake of counselling and testing is likely to be much greater in cancer prone families than those with other genetic disorders, yet detection and prevention strategies are still unevaluated for important genetically determined cancers such as breast cancer.

Attitude to Health↗

A social network analysis of communication about hereditary nonpolyposis colorectal cancer genetic testing and family functioning.

Hereditary cancers are relational diseases. A primary focus of research in the past has been the biological relations that exist within the families and how genes are passed along family lines. However, hereditary cancers are relational in a psychosocial sense, as well. They can impact communication relationships within a family, as well as support relationships among family members. Furthermore, the familial culture can affect an individual's participation in genetic counseling and testing endeavors. Our aims are (a) to describe the composition of familial networks, (b) to characterize the patterns of family functioning within families, (c) to analyze how these patterns relate to communications about genetic counseling and testing among family members, and (d) to identify influential family members. Specifically, we asked how the relationship between mutation status, kinship ties, and family functioning constructs, e.g., communication, cohesion, affective involvement, leadership, and conflict, was associated with discussions about genetic counseling and testing. We used social network analysis and random graph techniques to examine 783 dyadic relationships in 36 members of 5 hereditary nonpolyposis colorectal cancer (HNPCC) families interviewed from 1999-2000. Results suggest that in these five HNPCC families, two family members are more likely to discuss genetic counseling and testing if either one carries the mutation, if either one is a spouse or a first-degree relative of the other, or if the relationship is defined by positive cohesion, leadership, or lack of conflict. Furthermore, the family functioning patterns suggest that mothers tend to be the most influential persons in the family network. Results of this study suggest encouraging family members who act in the mother role to take a "team approach" with the family proband when discussing HNPCC risks and management with family members.

Adult↗

Development and validation of a Breast Cancer Genetic Counseling Knowledge Questionnaire.

Women who undergo genetic counseling concerning their increased risk of developing breast cancer confront large quantities of complex information in a short period of time. Clinical reports have suggested that many women may not retain what they learned during counseling. A validated questionnaire to measure their knowledge, however, is lacking. In this study, we describe the development and validation of a questionnaire to assess knowledge of information typically included in genetic counseling for breast cancer. Items were empirically derived from detailed content analyses of actual genetic counseling sessions. The instrument's content validity was high, as evidenced by high levels of independent interrater agreement (0.93) on items. Subsequent data reduction and confirmatory factor analytic techniques yielded a highly reliable (alpha = 0.92) 27-item Breast Cancer Genetic Counseling Knowledge Questionnaire (BGKQ). Direct comparison of this questionnaire to a scale previously developed in the literature (BCHK; [Breast Cancer Res. Treat. 53 (1999) 69]) supported the utility of the new questionnaire for evaluation of knowledge after counseling. Compared to non-counseled groups (n = 45), women who had undergone genetic counseling (n = 28) scored significantly higher (P < 0.0001) on the BGKQ, but not on the other questionnaire, establishing the BGKQ's criterion validity. The BGKQ may, thus, provide a useful clinical and research tool for assessing knowledge of information provided during genetic counseling and exploring the potential impact of distress on knowledge, as well as the impact of knowledge on screening behaviors.

Adult↗

Breast cancer genetics: what we know and what we need.

Breast cancer results from genetic and environmental factors leading to the accumulation of mutations in essential genes. Genetic predisposition may have a strong, almost singular effect, as with BRCA1 and BRCA2, or may represent the cumulative effects of multiple low-penetrance susceptibility alleles. Here we review high- and low-penetrance breast-cancer-susceptibility alleles and discuss ongoing efforts to identify additional susceptibility genes. Ultimately these discoveries will lead to individualized breast cancer risk assessment and a reduction in breast cancer incidence.

BRCA2 Protein↗

Progress of a Comprehensive Familial Cancer Genetic Counseling Program in the Era of BRCA1 and BRCA2.

BRCA1 and BRCA2 mutation carriers have an increased risk of developing breast and/or ovarian cancer. Technical advances in genetic testing have increased the need for genetic counseling services; therefore, we have developed a counseling program for these individuals. The purpose of this study is to characterize this population, assess level of interest in genetic testing, and evaluate our program over a 5-year period. Our Familial Cancer Genetic Counseling Program was established in November, 1994. Information was collected prospectively, with comprehensive evaluation including complete pedigree, risk assessment, and counseling by a genetic counselor, geneticist, and oncologist. Data were collected on risk level, and subsequent recommendations for screening and/or genetic testing. There were 824 contacts recorded from November, 1994, through August, 1999. To date, 162 families have undergone comprehensive genetic evaluation and counseling. 90 (56%) were seen for a concerning family history and 72 (44%) were seen due to a personal history of malignancy. The majority of families had a significant level of risk with 126 (78%) families having two and 70 (43%) families having three affected first-degree relatives. Of the 162 families who received full counseling, 125 (77%) met criteria to recommend BRCA1/BRCA2 genetic testing. At this time, 30 of the 162 (18%) have had genetic testing. A brief phone contact or clinic visit is useful to screen individuals so that counseling can be directed toward truly high-risk families. In our program, the majority of families counseled were eligible for BRCA1/BRCA2 testing, but only 18% have elected to proceed at this time.

Breast Neoplasms↗

Cancer genetics.

The fundamental ideas on the causes of cancer have been known for some time. They can now be interpreted in terms of the notion that cancer is essentially a genetic disease at the cellular level. The aim of this introductory article is to provide a brief overview of these ideas and the evidence for them, as well as some of the implications for future approaches to the prevention, early detection and treatment of cancer.

Family↗

Harnessing the potential of cancer genetics in healthcare.

The advancement of knowledge in genetics will have a profound effect on prediction, prevention, and treatment of cancer. It has the potential to offer more personalised healthcare that accords with an individual's genetic profile. However, the complex medical, ethical, legal, and psychosocial issues brought by our ability to test healthy individuals for cancer predisposition and the fast pace of advances in genetics pose great challenges to the medical community. Individuals and families are unlikely to benefit from an effective and ethical application of new genetic knowledge unless high quality cancer-genetics services are developed and integrated into mainstream healthcare, more research is undertaken into the prevention, causes, and treatment of cancer, and further efforts are made to improve public understanding and acceptance of cancer genetics.

Genetic Testing↗

Improving the referral process for familial breast cancer genetic counselling: findings of three randomised controlled trials of two interventions.

OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of two complementary interventions, using familial breast cancer as a model condition. The primary care intervention consisted of providing computerised referral guidelines and related education to GPs. The nurse counsellor intervention evaluated genetic nurses as substitutes for specialist geneticists in the initial assessment and management of referred patients. DESIGN: The computerised referral guidelines study was a pragmatic, cluster randomised controlled trial (RCT) with general practices randomised to intervention or control groups. The nurse counsellor intervention was tested in two concurrent RCTs conducted in separate UK health service locations, using predetermined definitions of equivalence. SETTING: The computerised referral guidelines trial took place in general practices in Scotland from November 2000 to June 2001. The nurse counsellor intervention took place in a regional genetics clinic in Scotland, and in two health authorities in Wales served by a single genetics service during 2001. PARTICIPANTS: The computerised referral guidelines study involved GPs and referred patients. Both nurse counsellor intervention trials included women referred for the first time, aged 18 years or over and whose main concern was family history of breast cancer. INTERVENTIONS: The software system was developed with GPs, presenting cancer genetic referral guidelines in a checklist approach. Intervention GPs were invited to postgraduate update education sessions, and both intervention and control practices received paper-based guidelines. The intervention period was November 2000 to June 2001. For the nurse counsellor trial, trial 1 ran outpatient sessions with the same appointment length as the standard service offered by geneticists, but the nurse counsellor saw new patients at the first appointment and referred back to the GP or on to a clinical geneticist according to locally developed protocol, under the supervision of a consultant geneticist. The control intervention was the current service, which comprised an initial and a follow-up appointment with a clinical geneticist. In trial 2, a nurse counsellor ran outpatient sessions with the same appointment length as the new consultant-based cancer genetics service and new patients were seen at the first appointment and referred as in trial 1. The control intervention was a new service, and comprised collection of family history by telephone followed by a consultation with a clinical assistant or a specialist registrar, supervised by a consultant. The intervention was implemented between 1998 and 2001. MAIN OUTCOME MEASURES: In the software system trial, the primary outcome was GPs' confidence in their management of patients with concerns about family history of breast cancer. For the nurse counsellor trial, the primary outcome was patient anxiety, measured using standard scales. RESULTS: In the software system trial, 57 practices (230 GPs) were randomised to the intervention group and 29 (116 GPs) to the control group. No statistically significant differences were detected in GPs' confidence or any other outcomes. Fewer than half of the intervention GPs were aware of the software, and only 22 reported using it in practice. The estimated total cost was GBP3.12 per CD-ROM distributed (2001 prices). For the two arms of the nurse counsellor trial, 289 patients (193 intervention, 96 control) and 297 patients (197 intervention and 100 control) consented, were randomised, returned a baseline questionnaire and attended the clinic for trials 1 and 2 respectively. The analysis in both cases suggested equivalence in all anxiety scores, and no statistically significant differences were detected in other outcomes in either trial. A cost-minimisation analysis suggested that the cost per counselling episode was GBP10.23 lower in intervention arm than in the control arm and GBP10.89 higher in the intervention arm than in the control arm (2001 prices) for trials 1 and 2, respectively. Taking the trials together, the costs were sensitive to the grades of doctors and the time spent in consultant supervision of the nurse counsellor, but they were only slightly affected by the grade of nurse counsellor, the selected discount rate and the lifespan of equipment. CONCLUSIONS: Computer-based systems in the primary care intervention cannot be recommended for widespread use without further evaluation and testing in real practice settings. Genetic nurse counsellors may be a cost-effective alternative to assessment by doctors. This trial does not provide definitive evidence that the general policy of employing genetics nurse counsellors is sound, as it was based on only three individuals. Future evaluations of computer-based decision support systems for primary care must first address their efficacy under ideal conditions, identify barriers to the use of such systems in practice, and provide evidence of the impact of the policy of such systems in routine practice. The nurse counsellor trial should be replicated in other settings to provide reassurance of the generalisability of the intervention and other models of nurse-based assessment, such as in outreach clinics, should be developed and evaluated. The design of future evaluations of professional substitution should also address issues such as the effect of different levels of training and experience of nurse counsellors, and learning effects.

Breast Neoplasms↗

Lung cancer: genetics of risk and advances in chemoprevention.

PURPOSE OF REVIEW: The current article reviews recent advances in genetic susceptibility and chemoprevention of lung cancer. RECENT FINDINGS: Linkage analysis has identified a locus on chromosome 6q23-25 that determines susceptibility to lung cancer in families with multiple members with cancer of the lung, throat, and larynx. Obligate gene carriers are sensitive to even small tobacco smoke exposure in terms of increased lung cancer risk. Variation in other genes, particularly those regulating the activation or inactivation of carcinogens, has been implicated in determining lung cancer risk. Epidemiologic and preclinical studies suggest that chemoprevention of lung cancer is an achievable goal. Early trials with beta-carotene supplementation, however, have revealed a harmful effect. Promising new agents must be evaluated in both preclinical models and in intermediate end point biomarker trials before being taken to large primary prevention trials, and lung cancer chemoprevention should only be attempted within controlled clinical trials. SUMMARY: We are poised to learn a great deal about the genetic susceptibility to lung cancer, which will not only allow definition of groups with extremely high risk, but may also yield new insights into processes that determine innate susceptibility or resistance to lung carcinogenesis. Chemoprevention of lung cancer is not yet ready for clinical application. As a result of the large number of lung cancer deaths and the large number of at-risk individuals, even modestly effective chemoprevention could save many lives.

Animals↗

Cancer genetics in the new era of molecular biology.

The role of primary genetic factors in the etiology of cancer has become of intense interest to the research and clinical community. This interest has been heightened by recent discoveries that germ-line mutations such as BRCA1 and BRCA2 in hereditary breast cancer are responsible for an increasing percentage of common solid tumors. A potpourri of proto-oncogenes and tumor-suppressor genes has been identified in hereditary as well as certain common sporadic and rare cancer types, and new cancer genes will likely be discovered every month to account for the 5 to 10% of the cases of cancer that can be attributed to primary genetic factors. Molecular mechanisms in the pathogenesis of hereditary cancer can result in more-targeted cancer-control measures. At least four mutator genes (MHS2, MLH1, PMS1 and PMS2) appear to account for 70-80% of hereditary nonpolypoid colorectal cancer (HNPCC). When one of these germ-line mutations is present in an HNPCC family, the physician is then able to determine the patient's lifetime cancer destiny with an accuracy of about 90% (limited only by the penetrance of the gene). This will enable highly targeted surveillance to be initiated early, such as colonoscopy beginning at ages 20 to 25 or prophylactic subtotal colectomy. Also, in multiple endocrine neoplasia syndromes (MEN 2A and 2B), the identification of the culprit RET proto-oncogene now enables a secure diagnosis and permits testing of children who might benefit from prophylactic total thyroidectomy. Central to translation of these momentous molecular genetic discoveries into patient care is the necessity of determining who requires DNA testing. The cancer family history is the linchpin in making this decision.

Adaptor Proteins, Signal Transducing↗

[BRCA1 Gene's Mutations And Hereditary Breast Cancer: Genetic, Biological, And Clinical Aspects].

INTRODUCTION: Hereditary breast cancer accounts for approximately 5 to 10% of all breast cancer cases. Mutations in the BRCA1 gene, which plays a central role in DNA repair and cell cycle regulation, are the main cause of these familial forms and are strongly associated with aggressive subtypes, particularly triple-negative breast cancer. METHODS: A narrative literature review was conducted using biomedical databases (PubMed, Scopus, Web of Science, Google Scholar) between January 2024 and June 2025. Eligible publications addressed the genetic, biological, epidemiological, and clinical aspects of BRCA1 in hereditary breast cancer. RESULTS: BRCA1 ensures genomic stability through its roles in DNA repair, cell cycle checkpoints, and transcriptional regulation. Most mutations are truncating or missense variants, with some reported as founder mutations (e.g., c.68_69delAG, c.5266dupC, 943ins10). Women carrying germline BRCA1 mutations have an estimated lifetime risk of 56-87% of developing breast cancer, with a strong association with aggressive molecular subtypes, especially triple-negative breast cancer. CONCLUSION: A comprehensive understanding of BRCA1 mutations is crucial to enhance prevention, screening, and personalized management of hereditary breast cancer. In low-resource settings, the integration of genetic testing and counseling remains a major challenge and a public health priority to reduce disparities in cancer care.

Humans↗

Facts in cancer genetics.

During the past decade molecular biology and molecular genetics have greatly increased our understanding of the basic mechanisms in cancer development. The essential outcome of these molecular studies is that cancer can be considered as a genetic disease of cells. Both the non-hereditary (sporadic) cancers, as well as the hereditary forms of cancer are caused by genetic accidents that perturb the complex and delicate cellular growth control systems. Thus, at the molecular level, no principal difference exists between hereditary- and non-hereditary forms of cancer and it can be stated that both at the level of the single cell as well at the level of the individual, cancer is a genetic disease. Whereas in hereditary cancer, the risk gene is passed through the germline to the next generation, in sporadic cancer, a cancer cells passes its abnormal genes to its daughter cells at cell division. It is therefore not surprising that one of the main priorities in cancer research today is the identification of the culprit genes and characterizing the function of their normal products. Genes associated with hereditary cancer syndromes essentially encompass two classes of genes viz. tumor suppressor genes and genes controlling genomic stability (DNA-mismatch repair genes). Although germline mutations in these susceptibility genes are associated with significantly increased cancer risk, even up to 90%, additional genetic factors and interaction with environmental factors eventually determine if a carrier of a germline mutation will develop cancer.

Counseling↗