Cancer Genetics Overview (PDQ®)
- Genetic Counseling
- Familial Cancer Susceptibility Syndromes
- Methods of Genetic Analysis and Gene Discovery
- Structure and Content of PDQ Summaries
- Genetic Resources
- Changes to This Summary (02/14/2013)
- About This PDQ Summary
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Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms. When a linked term is clicked, the definition will appear in a separate window.
The etiology of cancer is multifactorial, with genetic, environmental, medical, and lifestyle factors interacting to produce a given malignancy. Knowledge of cancer genetics is rapidly improving our understanding of cancer biology, helping to identify at-risk individuals, furthering the ability to characterize malignancies, establishing treatment tailored to the molecular fingerprint of the disease, and leading to the development of new therapeutic modalities. As a consequence, this expanding knowledge base has implications for all aspects of cancer management, including prevention, screening, and treatment.
Genetic information provides a means to identify people who have an increased risk of cancer. Sources of genetic information include biologic samples of DNA, information derived from a person’s family history of disease, findings from physical examinations, and medical records. DNA-based information can be gathered, stored, and analyzed at any time during an individual’s life span, from before conception to after death. Family history may identify people with a modest to moderately increased risk of cancer or may serve as the first step in the identification of an inherited cancer predisposition that confers a very high lifetime risk of cancer. For an increasing number of diseases, DNA-based testing can be used to identify a specific mutation as the cause of inherited risk and to determine whether family members have inherited the disease-related mutation.
Throughout this summary, the term “mutation” will be used to refer to a change in the usual DNA sequence of a particular gene. Mutations can have harmful, beneficial, neutral, or uncertain effects on health and may be inherited as autosomal dominant, autosomal recessive, or X-linked traits. Mutations that cause serious disability early in life are usually rare because of their adverse effect on life expectancy and reproduction. However, if the mutation is autosomal recessive—that is, if the health effect of the mutation is caused only when two copies (one from each parent) of the mutated gene are inherited—mutation carriers (healthy people carrying one copy of the altered gene) may be relatively common in the general population. "Common" in this context refers, by convention, to a prevalence of 1% or more. Mutations that cause health effects in middle and older age, including several mutations known to cause a predisposition to cancer, may also be relatively common. Many cancer-predisposing traits are inherited in an autosomal dominant fashion, that is, the cancer susceptibility occurs when only one copy of the altered gene is inherited. For autosomal dominant conditions, the term “carrier” is often used in a less formal manner to denote people who have inherited the genetic predisposition conferred by the mutation. Refer to individual PDQ summaries focused on the genetics of specific cancers for detailed information on known cancer-susceptibility syndromes.
Increasingly, the public is turning to the Internet for information related both to familial and genetic susceptibility to cancer and to genetic risk assessment and testing. Direct-to-consumer marketing of genetic testing for hereditary breast and colon cancer is also taking place in some communities. This wider availability of information related to inherited cancer risk may raise concerns among persons previously unaware of the implications inherent in their family histories and may lead some of these individuals to consult their primary care physicians for management advice and recommendations. In many instances, the evaluation and advice will be relatively straightforward for physicians with a basic knowledge of familial cancer. In a subset of patients, the evaluation may be more complex, calling for referral to genetics professionals for further evaluation and counseling.
Correctly recognizing and identifying individuals and families at increased risk of developing cancer is one of countless important roles for primary care and other health care providers. Once identified, these individuals can then be appropriately referred for genetic counseling, risk assessment, consideration of genetic testing, and development of a management plan. When medical and family histories reveal cardinal clues to the presence of an underlying familial or genetic cancer susceptibility disorder (see list below), further evaluation may be warranted. (Refer to the PDQ summary on Cancer Genetics Risk Assessment and Counseling for more information about the components of a genetics cancer risk assessment.)
Features of hereditary cancer include the following:
- In the individual patient:Multiple primary tumors in the same organ.Multiple primary tumors in different organs.Bilateral primary tumors in paired organs.Multifocality within a single organ (e.g., multiple tumors in the same breast, all of which have risen from one original tumor).Younger-than-usual age at tumor diagnosis.Tumors with rare histology.Tumors occurring in the sex not usually affected (e.g., breast cancer in men).Tumors associated with other genetic traits.Tumors associated with congenital defects.Tumors associated with an inherited precursor lesion.Tumors associated with another rare disease.Tumors associated with cutaneous lesions known to be related to cancer susceptibility disorders (e.g., the genodermatoses).
- In the patient’s family:One first-degree relative with the same or a related tumor and one of the individual features listed.Two or more first-degree relatives with tumors of the same site.Two or more first-degree relatives with tumor types belonging to a known familial cancer syndrome.Two or more first-degree relatives with rare tumors.Three or more relatives in two generations with tumors of the same site or etiologically related sites.
Concluding that an individual is at increased risk of developing cancer may have important, potentially life-saving management implications and may lead to specific interventions aimed at reducing risk (e.g., tamoxifen for breast cancer, colonoscopy for colon cancer, or risk-reducing salpingo-oophorectomy for ovarian cancer). Information about familial cancer risk may also inform a person’s ability to plan for the future (lifestyle and health care decisions, family planning, or other decisions). Genetic information may also provide a direct health benefit by demonstrating the lack of an inherited cancer susceptibility. For example, if a family is known to carry a cancer-predisposing mutation in a particular gene, a family member may experience reduced worry and lower health care costs if his or her genetic test indicates that he or she does not carry the family’s disease-related mutation. Conversely, information about familial cancer risk may have psychological effects or social costs (e.g., worry, guilt, or increased health care costs). Family dynamics also may be affected. For instance, the involvement of one or more family members may be required for genetic testing to be informative, and parents may feel guilt about passing inherited risk on to their children.
Knowledge about a cancer-predisposing mutation can be informative not only for the individual tested but also for other family members. Family members who previously had not considered the implications of their family history for their own health may be led to do so, and some will undergo genetic testing, resulting in more definitive information on whether they are at increased genetic risk. Some relatives may learn their mutation status without being directly tested, for example, when a biological parent of a child who is a known mutation carrier is identified as an obligate carrier. Founder effects may result in the recognition that specific ethnic groups have a higher prevalence of certain mutations, knowledge that can be either clinically useful (permitting more rational genetic testing strategies) or potentially stigmatizing. Testing may reveal the presence of nonpaternity in a family. There is the theoretical possibility that genetic information may be misused, and concerns about the potential for insurance and/or employment discrimination may arise. Genetic information may also affect medical and lifestyle decisions.
Refer to individual PDQ summaries for available evidence addressing all ancillary issues.1Lindor NM, McMaster ML, Lindor CJ, et al.: Concise handbook of familial cancer susceptibility syndromes - second edition. J Natl Cancer Inst Monogr (38): 1-93, 2008.
Genetic counseling is a process of communication between genetics professionals and patients with the goal of providing individuals and families with information on the relevant aspects of their genetic health, available testing and management options, and support as they move toward understanding and incorporating this information into their daily lives. Genetic counseling generally involves the following six steps:
- Family and medical history assessment.
- Analysis of genetic information.
- Communication of genetic information.
- Education about inheritance, genetic testing, management, risk reduction, resources, and research opportunities.
- Supportive counseling to facilitate informed choices and adaptation to the risk or condition.
- Follow up.
Genetic evaluation involves an interaction with a medical geneticist or other genetics professional and may include a physical examination and diagnostic testing, in addition to genetic counseling. The principles of voluntary and informed decision making, nondirective and noncoercive counseling, and protection of client confidentiality and privacy are central to the philosophy of genetic counseling. (Refer to the PDQ summary on Cancer Genetics Risk Assessment and Counseling for more information on the nature and history of genetic counseling.)
From the mid-1990s to the mid-2000s, genetic counseling expanded to include discussion of genetic testing for cancer risk, as more genes associated with inherited cancer risk were discovered. Cancer genetic counseling often involves a multidisciplinary team of health professionals that may include a genetic counselor, an advanced practice genetics nurse, or a medical geneticist; a mental health professional; and various medical experts such as an oncologist, surgeon, or internist. The process of counseling may require a number of visits to address medical, genetic testing, and psychosocial issues. Even when cancer risk counseling is initiated by an individual, inherited cancer risk has implications for the entire family. Because genetic risk affects biological relatives, contact with these relatives is often essential to collect accurate family and medical histories. Cancer genetic counseling may involve several family members, some of whom will have had cancer and others who have not.
The impact of risk assessment and predisposition genetic testing is improved health outcomes. The information derived from risk assessment and/or genetic testing allows the health care provider to tailor an individual approach to health promotion and optimize long-term health outcomes through the identification of at-risk individuals before cancer develops. The health care provider can thus intervene earlier either to reduce the risk or diagnose a cancer at an earlier stage, when the chances for effective treatment are greatest. The information may be used to modify the management approach to an initial cancer, clarify the risks of other cancers, or predict the response of an existing cancer to specific forms of treatment, all of which may alter treatment recommendations and long-term follow-up.1Resta R, Biesecker BB, Bennett RL, et al.: A new definition of Genetic Counseling: National Society of Genetic Counselors' Task Force report. J Genet Couns 15 (2): 77-83, 2006.2Baker DL, Schuette JL, Uhlmann WR, eds.: A Guide to Genetic Counseling. New York, NY: Wiley-Liss, 1998.3Bartels DM, LeRoy BS, Caplan AL, eds.: Prescribing Our Future: Ethical Challenges in Genetic Counseling. New York, NY: Aldine de Gruyter, 1993.4Kenen RH: Genetic counseling: the development of a new interdisciplinary occupational field. Soc Sci Med 18 (7): 541-9, 1984.5Kenen RH, Smith AC: Genetic counseling for the next 25 years: models for the future. J Genet Couns 4(2): 115-124, 1995.
Familial Cancer Susceptibility Syndromes
Individual PDQ summaries focused on the genetics of specific cancers contain detailed information about many known cancer susceptibility syndromes. Although this is not a complete list, the following cancer susceptibility syndromes are discussed in the PDQ cancer genetics summaries (listed in parentheses following the syndromes):
- Basal Cell Nevus Syndrome, Gorlin Syndrome, Gorlin-Goltz Syndrome, or Nevoid Basal Cell Carcinoma Syndrome (Genetics of Skin Cancer).
- Bloom Syndrome (Genetics of Skin Cancer).
- Breast/Ovarian Cancer, Hereditary (Genetics of Breast and Ovarian Cancer).
- Colon Cancer, Hereditary Nonpolyposis or Lynch Syndrome (Genetics of Colorectal Cancer).
- Cowden Syndrome (Genetics of Breast and Ovarian Cancer; Genetics of Colorectal Cancer).
- Fanconi Anemia (Genetics of Skin Cancer).
- Hyperparathyroidism, Familial (Genetics of Endocrine and Neuroendocrine Neoplasias).
- Li-Fraumeni Syndrome (Genetics of Breast and Ovarian Cancer).
- Medullary Thyroid Cancer, Familial (Genetics of Endocrine and Neuroendocrine Neoplasias).
- Melanoma, Hereditary (Genetics of Skin Cancer).
- Multiple Endocrine Neoplasia Type 1 (Genetics of Endocrine and Neuroendocrine Neoplasias).
- Multiple Endocrine Neoplasia Type 2A, 2B (Sipple Syndrome) (Genetics of Endocrine and Neuroendocrine Neoplasias).
- Peutz-Jeghers Syndrome (Genetics of Colorectal Cancer; Genetics of Breast and Ovarian Cancer).
- Polyposis, Familial Adenomatous and Attenuated Familial Adenomatous Polyposis (Genetics of Colorectal Cancer).
- Polyposis, Familial Juvenile (Genetics of Colorectal Cancer).
- Polyposis, MYH-Associated (Genetics of Colorectal Cancer).
- Prostate Cancer, Hereditary (Genetics of Prostate Cancer).
- Xeroderma Pigmentosum (Genetics of Skin Cancer).
Methods of Genetic Analysis and Gene Discovery
The recognition that cancer clusters within families has led many investigators to collect data on multiple-case families with the goal of localizing cancer susceptibility genes through linkage studies.
Linkage studies are typically performed on high-risk kindreds, in whom multiple cases of a particular disease have occurred, in an effort to identify disease susceptibility genes. Linkage analysis statistically compares the genotypes between affected and unaffected individuals and looks for evidence that known genetic markers are inherited along with the disease trait. If such evidence is found (linkage), it provides statistical data that the chromosomal region near the marker also harbors a disease susceptibility gene. Once a genomic region of interest has been identified through linkage analysis, additional studies are required to prove that there truly is a susceptibility gene at that position. Linkage analysis is affected by the following:
- Family size and having a sufficient number of family members who volunteer to contribute DNA.
- The number of disease cases in each family.
- Factors related to age at disease onset (e.g., utilization of screening).
- Gender differences in disease risk (not relevant in gender-specific cancers).
- Heterogeneity of disease in cases (e.g., aggressive vs. nonaggressive phenotype).
- The accuracy of family history information.
- Prevalence of phenocopies.
An additional issue in linkage studies is the background rate of sporadic cancer in the context of family studies. For example, because a man’s lifetime risk of prostate cancer is one in six, it is possible that families under study have both inherited and sporadic prostate cancer cases. Thus, men who do not inherit the prostate cancer susceptibility gene that is segregating in their family may still develop prostate cancer.
One way to address inconsistencies between linkage studies is to require inclusion criteria that defines clinically significant disease. This approach attempts to define a homogeneous set of cases/families to increase the likelihood of identifying a linkage signal. It also prevents the inclusion of cases that may be considered clinically insignificant that were identified by screening in families.
Investigators have also incorporated clinical parameters into linkage analyses with the goal of identifying genes that may influence disease severity. This type of approach, however, has not yet led to the identification of consistent linkage signals across datasets.
Genome-wide Association Studies (GWAS)
GWAS are showing great promise in identifying common, low-penetrance susceptibility alleles for many complex diseases, including cancer. This approach can be contrasted with linkage analysis, which searches for genetic-risk variants cosegregating within families that have a high prevalence of disease. While linkage analyses are designed to uncover rare, highly penetrant variants that segregate in predictable heritance patterns (e.g., autosomal dominant, autosomal recessive, X-linked, and mitochondrial), GWAS are best suited to identify multiple, common, low-penetrance genetic polymorphisms. GWAS are conducted under the assumption that the genetic underpinnings of complex phenotypes, such as prostate cancer, are governed by many alleles, each conferring modest risk. Most genetic polymorphisms genotyped in GWAS are common, with minor allele frequencies greater than 1% to 5% within a given population (e.g., men of European ancestry). GWAS capture a large portion of common variation across the genome. The strong correlation between many alleles located close to one another on a given chromosome (called linkage disequilibrium) allows one to “scan” the genome without having to test all 10 million known single nucleotide polymorphisms (SNPs). With GWAS, researchers can test 500,000 to 1 million SNPs per study and ascertain almost all common inherited variants in the genome.
In a GWAS, allele frequency for each SNP is compared between cases and controls. Promising signals—in which allele frequencies deviate significantly in case and control populations—are validated in replication cohorts. To have adequate statistical power to identify variants associated with a phenotype, large numbers of cases and controls, typically thousands of each, are studied. Because up to 1 million SNPs are evaluated in a GWAS, false-positive findings are expected to occur frequently when using standard statistical thresholds. Therefore, stringent statistical rules are used to declare a positive finding, usually using a threshold of P < 1 × 10-7.
To date, well over 100 cancer-risk variants have been identified by well-powered GWAS and validated in independent cohorts. These studies have revealed convincing associations between specific inherited variants and cancer risk. However, the findings should be qualified with a few important considerations:
- GWAS reported thus far have been designed to identify relatively common genetic polymorphisms. It is very unlikely that an allele with high frequency in the population by itself contributes substantially to cancer risk. This, coupled with the polygenic nature of tumorigenesis, means that the contribution by any single variant identified by GWAS to date is quite small, generally with an odds ratio for disease risk of less than 1.5. In addition, despite extensive genome-wide interrogation of common polymorphisms in tens of thousands of cases and controls, GWAS findings to date do not account for even half of the genetic component of cancer risk.
- Variants uncovered by GWAS are not likely to directly contribute to disease risk. As mentioned above, SNPs exist in linkage disequilibrium blocks and are merely proxies for a set of variants—both known and previously undiscovered—within a given block. The causal allele is located somewhere within that linkage disequilibrium block.
- Admixture by groups of different ancestry can confound GWAS findings (i.e., a statistically significant finding could reflect a disproportionate number of subjects in the cases versus controls, rather than a true association with disease). Therefore, GWAS are typically powered to analyze a single predominant ancestral group. As a result, many populations remain underrepresented in genome-wide analyses.
The implications of these points are discussed in greater detail in the PDQ summaries on Genetics of Breast and Ovarian Cancer; Genetics of Colorectal Cancer; and Genetics of Prostate Cancer. Additional details can be found elsewhere.1American Cancer Society.: Cancer Facts and Figures 2013. Atlanta, Ga: American Cancer Society, 2013. Available online. Last accessed May 2, 2013.2Stanford JL, McDonnell SK, Friedrichsen DM, et al.: Prostate cancer and genetic susceptibility: a genome scan incorporating disease aggressiveness. Prostate 66 (3): 317-25, 2006.3Chang BL, Isaacs SD, Wiley KE, et al.: Genome-wide screen for prostate cancer susceptibility genes in men with clinically significant disease. Prostate 64 (4): 356-61, 2005.4Lange EM, Ho LA, Beebe-Dimmer JL, et al.: Genome-wide linkage scan for prostate cancer susceptibility genes in men with aggressive disease: significant evidence for linkage at chromosome 15q12. Hum Genet 119 (4): 400-7, 2006.5Witte JS, Goddard KA, Conti DV, et al.: Genomewide scan for prostate cancer-aggressiveness loci. Am J Hum Genet 67 (1): 92-9, 2000.6Witte JS, Suarez BK, Thiel B, et al.: Genome-wide scan of brothers: replication and fine mapping of prostate cancer susceptibility and aggressiveness loci. Prostate 57 (4): 298-308, 2003.7Slager SL, Zarfas KE, Brown WM, et al.: Genome-wide linkage scan for prostate cancer aggressiveness loci using families from the University of Michigan Prostate Cancer Genetics Project. Prostate 66 (2): 173-9, 2006.8Slager SL, Schaid DJ, Cunningham JM, et al.: Confirmation of linkage of prostate cancer aggressiveness with chromosome 19q. Am J Hum Genet 72 (3): 759-62, 2003.9Wellcome Trust Case Control Consortium.: Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447 (7145): 661-78, 2007.10The International HapMap Consortium.: The International HapMap Project. Nature 426 (6968): 789-96, 2003.11Thorisson GA, Smith AV, Krishnan L, et al.: The International HapMap Project Web site. Genome Res 15 (11): 1592-3, 2005.12Evans DM, Cardon LR: Genome-wide association: a promising start to a long race. Trends Genet 22 (7): 350-4, 2006.13Cardon LR: Genetics. Delivering new disease genes. Science 314 (5804): 1403-5, 2006.14Chanock SJ, Manolio T, Boehnke M, et al.: Replicating genotype-phenotype associations. Nature 447 (7145): 655-60, 2007.15Ioannidis JP, Castaldi P, Evangelou E: A compendium of genome-wide associations for cancer: critical synopsis and reappraisal. J Natl Cancer Inst 102 (12): 846-58, 2010.16Jorgenson E, Witte JS: Genome-wide association studies of cancer. Future Oncol 3 (4): 419-27, 2007.
Structure and Content of PDQ Summaries
PDQ cancer genetics summaries focus on the genetics of specific cancers, inherited cancer syndromes, and the ethical, social, and psychological implications of cancer genetics knowledge. Sections on the genetics of specific cancers include syndrome-specific information on the risk implications of a family history of cancer, the prevalence and characteristics of cancer-predisposing mutations, known modifiers of genetic risk, opportunities for genetic testing, outcomes of genetic counseling and testing, and interventions available for people with increased cancer risk resulting from an inherited predisposition.
The source of medical literature cited in PDQ cancer genetics summaries is peer-reviewed scientific publications, the quality and reliability of which is evaluated in terms of levels of evidence. Where relevant, the level of evidence is cited, or particular strengths of a study or limitations of the evidence are described.
Refer to the Levels of Evidence for Cancer Genetics Studies summary for more information on the levels of evidence utilized in the PDQ cancer genetics summaries.
Health care providers who deliver genetic services, including genetic counseling, can be located through local, regional, and national professional genetics organizations; through the NCI Web site Cancer Genetics Services Directory; and through the GeneTests Web site. Providers of cancer genetic services are not limited to one specialty and include medical geneticists, genetic counselors, advanced practice genetics nurses, oncologists (medical, radiation, or surgical), other surgeons, internists, family practitioners, and mental health professionals. A cancer genetics health care provider will assist in constructing and evaluating a pedigree, eliciting and evaluating personal and family medical histories, and calculating and providing information about cancer risk and/or probability of a mutation being associated with cancer in the family. In addition, if a genetic test is available, these providers can assist in pretest counseling, laboratory selection, informed consent, test interpretation, posttest counseling, and follow-up. The printable view of this summary contains a Table of Links at the end of the summary with the URLs of the Web sites listed in the Genetics Resources section.Table 1. Clinical Genetics Information ResourceDescriptionGeneTestsInformation for health professionals about hundreds of genetic tests and the laboratories performing those tests.Human Genome Epidemiology Network (HuGENet)Network for sharing population-based human genome epidemiologic information.National Institutes of Health Genetic Testing Registry (GTR)Central location for voluntary submission of genetic test information by providers. The scope includes the test's purpose, methodology, validity, evidence of the test's usefulness, and laboratory contacts and credentials.Online Mendelian Inheritance in Man (OMIM)Catalog of human genes and genetic disorders.Table 2. Clinical Management InformationResourceDescriptionClinical Practice Guidelines from the American College of Medical Genetics (ACMG)Clinical practice guidelines developed by expert panels for risk assessment, testing, and counseling of individuals with various inherited conditions, including some cancers, or individuals with a high risk of developing these conditions.Clinical Practice Guidelines from the American Society of Clinical Oncology (ASCO)Clinical practice guidelines developed by expert panels for specific clinical situations (disease-oriented) or use of approved medical products, procedures, or tests (modality-oriented).National Comprehensive Cancer Network (NCCN) GuidelinesClinical practice guidelines developed by expert panels that detail the sequential management decisions and interventions for the malignant cancers that affect 97% of all patients with cancer. In addition, separate guidelines relate to major prevention and screening topics, and another set of pathways focuses on the major supportive care areas.National Guideline Clearinghouse from the Agency for Healthcare Research and Quality (AHRQ)A public resource for evidence-based clinical practice guidelines.Table 3. Consumer/Client: General InformationResourceDescription Cancer Genetics Services Directory (National Cancer Institute [NCI])Directory lists professionals who provide cancer genetics services (cancer risk assessment, genetic counseling, genetic susceptibility testing, and others). Dictionary of Genetics Terms (NCI)Definitions of more than 150 terms related to genetics. The DNA FilesSeries of 14 one-hour public radio documentaries and related information.Dolan DNA Learning Center Variety of educational resources, including an interactive DNA timeline.Facing Our Risk of Cancer Empowered (FORCE)Support and information to individuals and families affected by hereditary breast and ovarian cancer through a toll-free help line, message boards, chat rooms, and support groups. Genetic and Rare Diseases Information Center (National Human Genome Research Institute [NHGRI]):Information service for the general public, including patients and their families, and for health care professionals and biomedical researchers.Genetic Science Learning Center (The University of Utah) Information about basic genetics, genetic disorders, genetics in society, and several thematic units.Genetics Education CenterMaterial for educators.Genetics Home Reference (National Library of Medicine)Consumer information about genetic conditions and the genes or chromosomes responsible for those conditions.Talking Glossary of Genetics Terms (NHGRI)Contains definitions of more than 200 terms related to genetics and a quiz to test your knowledge of genetic terminology. Many terms also have images, animations, and descriptions by specialists in the field of genetics.Understanding Cancer Series (NCI)Primers on cancer genomics, genetic testing, genome-wide profiling, and other topics. Understanding the Human Genome Project (NHGRI)An education kit that includes a dynamic timeline, a 3-D computer-animated video on basic molecular biology, and other classroom activities.Table 4. Ethical, Legal, and Social Implications; Policy; and Legislation InformationResourceDescriptionbioethics.netLinks to articles on genetics and bioethics.Bioethics Resources on the WebLinks to bioethics resources.DNA Patent DatabaseSearchable database of U.S. DNA-based patents and patent applications issued by the U.S. Patent and Patent Applications Trademark Office.Ethical, Legal, and Social Issues (U.S. Department of Energy) Information, articles, and links on a wide range of genetics issues.Genethics.caInformation on the social, ethical, and policy issues associated with genetic and genomic knowledge and technology.Genetic Information Nondiscrimination Act (GINA) of 2008 (National Human Genome Research Institute [NHGRI])Fact sheet that describes genetic discrimination and GINA for the public.GINA: An Overview (Coalition for Genetic Fairness)Describes GINA’s protections, including a history of the legislation, key examples, and definitions.GINA of 2008 Information for Researchers and Health Care Professionals (NHGRI)Fact sheet that describes GINA for researchers and health professionals.Genetics and Public Policy CenterInformation on public policy related to human genetic technologies for the public, media, and policy makers.Genome Technology and Reproduction: Values and Public Policy and Communities of Color and Genetics Policy ProjectTwo subprojects combined to form a 5-year project designed to provide policy recommendations based on public perceptions and responses to the explosion of genetic information and technology. HumGen InternationalComprehensive international database on the legal, social, and ethical aspects of human genetics.National Conference of State Legislatures Genetic Technologies ProjectResources on a variety of genetics public policy and related issues for state legislators, legislative staff, and other policy makers.National Information Resource on Ethics and Human Genetics (Georgetown University)Links to resources and databases on ethics and human genetics. Also includes annotated bibliographies on various genetics and ethics issues.National Society of Genetic Counselors Code of Ethics A statement to clarify and guide the ethical conduct of genetic counselors.Policy and Legislation Database (NHGRI)Searchable database of federal and state laws/statutes, federal legislative materials, and federal administrative and executive materials about privacy of genetic information/confidentiality; informed consent; insurance and employment discrimination; genetic testing and counseling; and commercialization and patenting.THOMAS Legislative Information (The Library of Congress)Searchable database of U.S. legislation (current and previous Congresses).Your Genes, Your Choices: Exploring the Issues Raised by Genetic ResearchDescription of the Human Genome Project, the science behind it, and the ethical, legal, and social issues raised by the project.Table 5. Family History ToolsResourceDescriptionFamily Health History (Genetic Alliance)Tips for collecting family history information and links to resources.Family History Public Health Initiative (Centers for Disease Control and Prevention)Web site devoted to using family history to promote health.Family Medical History (American Medical Association)Tools for gathering family history and links to resources.My Family Health Portrait (U.S. Surgeon General)Web-based family history tool.Your Family History (National Society of Genetic Counselors)Information on collecting a family health history.Table 6. Genome Research InformationResourceDescriptionBLAST = Basic Local Alignment Search Tool; COSMIC = Catalogue Of Somatic Mutations In Cancer; iHOP = information hyperlinked over proteins; SARS = severe acute respiratory syndrome; SNPs = single nucleotide polymorphisms; UCSC = University of California, Santa Cruz.BLAST Search (part of the Ensembl Project; see below)Search protein or DNA sequence against metazoan genomes.The Cancer Genome Anatomy Project (CGAP)Access to all CGAP data and biological resources.CancerGenes Combines gene lists annotated by experts with information from key public databases such as Entrez Gene, COSMIC, and iHOP.Cancer Genome Workbench (CGWB)Integrates clinical tumor mutation profiles with the reference human genome to improve the accuracy of mutation identification.Chromosomal Variation in ManSearchable database of literature citations on chromosomal variants and anomalies.Ensembl (Joint software project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute)Data sets resulting from an automated genome analysis and annotation process.Genome ChannelJava viewers for human genome data.Genome Sequencing Center: Homo sapiens MapsLinks to clone and accession maps of the human genome.International Cancer Genome Consortium Data PortalA collection of genome data from more than 25 cancer projects consisting of over 3,500 tumor genomes from 13 cancer types and subtypes. Most data are available with open access.International HapMap ProjectA variety of ways to query for SNPs in the human genome.Leiden Open Variation DatabaseA flexible, free tool for gene-centered collection, curation, and display of DNA variation.KMcancerDBHuman gene mutation database with graphical display of molecular information for cancer-related genes. National Center for Biotechnology Information: Genomic BiologyViews of chromosomes, maps, and loci; links to other NCBI resources.Online Mendelian Inheritance in Man (OMIM)Catalog of human genes and genetic disorders.UCSC Genome BioinformaticsReference sequence for the human and C. elegans genomes and working drafts for the mouse, rat, Fugu, Drosophila, C. briggsae, yeast, and SARS genomes. Table 7. Health Professional Practice and Genetic Education InformationResourceDescriptionCentre for Education in Medical GeneticsDevelops, provides, and evaluates genetics education opportunities and resources.Centre for Genetics EducationEducation and service resources for patients and professionals.Dolan DNA Learning CenterInteractive multimedia genetics education resources.Essentials of Genetic and Genomic Nursing: Competencies, Curricula Guidelines, and Outcome Indicators, 2nd editionEstablishes minimum basis to prepare the nursing workforce to deliver competent genetic and genomic-focused nursing care.Evaluation of Genomic Applications in Practice and Prevention (EGAPP)Provides an evidence-based review of genetic tests and other genomic applications that are in transition from research to clinical and public health practice in the United States.Genetics & Your PracticeOnline modules for health care professionals designed for exploration of a topic rather than a sequential presentation of material. Includes fact sheets and sample clinical forms. Free registration required for accessGenetics Education CenterOnline center for educators interested in human genetics and the Human Genome Project.Genetics Education Program for Nurses (GEPN)Sample genetics nursing course syllabi and other genetics educational opportunities and resources for nurses.Genetics/Genomics Competency Center for Education (G2C2)A repository of genetics/genomics education resources for nursing and physician assistant educators.Genetics in Clinical Practice: A Team Approach Interactive virtual genetics clinic with case scenarios and case discussions. Target audience is primary care professionals.Genetics in Primary CareTraining program curriculum materials.Genomic Applications in Practice and Prevention Network (GAPPNet)A collaborative initiative that aims to bring together stakeholders in order to accelerate and streamline effective and responsible use of validated and useful genomic knowledge and applications, such as genetic tests, technologies, and family history, into clinical and public health practice.Medical School Core Curriculum in GeneticsMedical school course competencies, skills, knowledge, and behaviors that should be covered in a genetics curriculum developed by the Association of Professors of Human and Medical Genetics and the American Society of Human Genetics.National Coalition for Health Professional Education in Genetics (NCHPEG)Core competencies in genetics and reviews of education programs. Descriptions of available instructional resources, courses, and institutes.Six Weeks to Genomic AwarenessWebcast of six lessons in genomics for public health professionals.Table 8. Institutional Review Boards (IRBs)ResourceDescriptionGenetic Testing and Screening in the Age of Genomic Medicine. New York State Task Force on Life and the Law.Includes general and state-specific information in a bulleted report.Pharmacogenetics: Ethical Issues. Nuffield Council on Bioethics.Includes a section discussing the use of pharmacogenetics in clinical trials.Protecting Human Research Subjects Institutional Review Board Guidebook, Chapter V, Section H: Human Genetic Research. Office for Human Research Protections.Discusses many issues that continue to challenge IRBs, investigators, and policy makers today.Table 9. Professional Organizations: GeneticsResourceDescriptionAmerican Board of Genetic Counseling (ABGC)Information about certification of genetic counselors.American Board of Medical Genetics (ABMG)Information about medical genetic training programs and certification of geneticists.American College of Medical Genetics (ACMG)Resources, policy statements, and practice guidelines about medical genetics.American Society for Human Genetics (ASHG)Resources, projects, and policies concerning human genetics.Genetics Nursing Credentialing Commission (GNCC)Information about credentialing of genetics nurses.Genetics Society of America (GSA)Links to teaching Web sites, general educational courses, and journals and publications about genetics.International Society of Nurses in Genetics (ISONG)Resources to help nurses incorporate new knowledge about human genetics into practice, education, and research.National Society of Genetic Counselors (NSGC)Information about genetic counseling: practice guidelines, links to genetic counselors, and genetic discrimination resources.Table 10. Risk Assessment InformationResourceDescriptionBreast Cancer Risk Assessment Tool (National Cancer Institute [NCI])Interactive tool for estimating a woman's risk of developing invasive breast cancer.Colorectal Cancer Risk Assessment Tool (NCI)Interactive tool for estimating the risk of developing colorectal cancer in a non-Hispanic white man or woman aged 50 to 85 years.Disease Risk Index (Harvard School of Public Health)Personalized estimation of cancer risk and tips for prevention.Family HealthLink (The Ohio State University Medical Center) Interactive tool that estimates cancer risk by reviewing patterns of cancer in a family.Melanoma Risk Assessment Tool (NCI)Interactive tool for estimating an individual’s absolute risk of developing melanoma.MyGenerationsInteractive tool that estimates cancer risk by reviewing patterns of cancer in a family. Table 11. Online Gene Mutation Prediction ProgramsResourceDescriptionHuGE = Human Genome Epidemiology; MMR = mismatch repair; MRC = Medical Research Council.HuGE Risk TranslatorCalculates the predictive value of genetic markers.MRC Human Genetics Unit, EdinburghPredicts the likelihood of mutations in one of the MMR genes in persons with colon cancer.The Penn II Risk ModelEstimates the probability that an individual has a BRCA1 or BRCA2 mutation.PREMM1,2,6 Model: Prediction Model for MLH1, MSH2, and MSH6 Gene MutationsEstimates the probability that an individual carries a mutation in one of the MMR genes.Table 12. Search Engines Specializing in Genetics and GenomicsResourceDescriptionGAMAdb = Genome-wide Association and Meta Analyses Database; GWAS = genome-wide association studies; HuGE = Human Genome Epidemiology; SNP = single nucleotide polymorphism.Cancer GAMAdbAn online database of published GWAS and meta-analyses for genetic polymorphisms and cancer risk.Catalog of Published Genome-Wide Association StudiesAn online catalog of SNP-trait associations from published GWAS for use in investigating genomic characteristics of trait/disease-associated SNPs.HuGE NavigatorAn integrated, searchable knowledge base of genetic associations and human genome epidemiology.National Information Resource on Ethics and Human Genetics (Georgetown University) Search engine for literature on specific issues related to ethics and human genetics.Table 13. United States Government AgenciesResourceDescriptionHRSA = Health Resources and Services Administration; NIH = National Institutes of Health.Centers for Disease Control and Prevention Office of Public Health GenomicsInformation on how human genomic discoveries can be used to improve health and prevent disease, including links to many resources.Genetic Modification Clinical Research Information System (GeMCRIS) Information about human gene transfer trials registered with NIH.National Cancer InstituteSummaries of cancer genetics–related information.National Human Genome Research InstituteResearch, policy, ethics, education, and training information and resources about genetic and rare diseases.U.S. Department of Energy Office of ScienceGenomics educational resources.U.S. Department of Health and Human ServicesLinks to publications and materials available for purchase or download from the HRSA Information Center.1Schully SD, Yu W, McCallum V, et al.: Cancer GAMAdb: database of cancer genetic associations from meta-analyses and genome-wide association studies. Eur J Hum Genet 19 (8): 928-30, 2011.
Changes to This Summary (02/14/2013)
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Methods of Genetic Analysis and Gene Discovery
Added American Cancer Society as reference 1.
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This information was last updated on 2013-02-14