[Note: Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms ¹. When a linked term is clicked, the definition will appear in a separate window.]

This summary describes current approaches to assessing and counseling people about their chance of having an inherited susceptibility to cancer. Genetic counseling is defined by the National Society of Genetic Counselors ² as the process of helping people understand and adapt to the medical, psychological, and familial implications of genetic contributions to disease. Several reviews present overviews of the cancer risk assessment, counseling and genetic testing process.[1-4].

Individuals are considered to be candidates for cancer risk assessment if they have a personal and/or family history in a maternal or paternal lineage with features suggestive of hereditary cancer.[5] These features vary by type of cancer and specific hereditary syndrome. Criteria have been published to help identify families who may benefit from a referral to genetic counseling.[2,6] The introductory sections of the PDQ cancer genetics information summaries on breast ³, ovarian ³, colorectal ⁴, prostate ⁵, skin ⁶, and medullary thyroid ⁷ cancers describe the clinical features of hereditary syndromes associated with these cancers.

The following are features that suggest hereditary cancer:

• Unusually early age of cancer onset (e.g., premenopausal breast cancer).
• Multiple primary cancers in a single individual (e.g., colorectal and endometrial cancer).
• Bilateral cancer in paired organs, or multifocal disease (e.g., bilateral breast cancer or multifocal renal cancer).
• Clustering of the same type of cancer in close relatives (e.g., mother, daughter and sisters with breast cancer).
• Cancers occurring in multiple generations of a family (autosomal dominant inheritance).
• Occurrence of rare tumors (e.g., retinoblastoma, adrenocortical carcinoma, granulosa cell tumor of the ovary, ocular melanoma, hepatoma, or duodenal cancer).
• Unusual presentation of cancer (e.g., male breast cancer).
• Uncommon tumor histology (e.g., medullary thyroid carcinoma).
• Rare cancers associated with birth defects (e.g., Wilms tumor and genitourinary abnormalities).
• Geographic or ethnic populations known to be at high risk of hereditary cancers. Genetic testing candidates may be identified based solely on ethnicity when a strong founder effect is present in a given population (e.g., Ashkenazi heritage and BRCA1/BRCA2 mutations).[7,8]

As part of the process of genetic education and counseling, genetic testing may be considered when the following factors are present:

• An individual's personal history (including ethnicity) and/or family history is suspicious for a genetic predisposition to cancer.
• The genetic test has sufficient sensitivity and specificity to be interpreted.
• The test will impact the individual's diagnosis, cancer management or cancer risk management, and/or help clarify risk for family members.[9]

A candidate for genetic testing receives genetic education and counseling before testing to facilitate informed decision making and adaptation to the risk or condition.[10] Genetic education and counseling gives an individual time to consider the various medical uncertainties, diagnosis, or medical management based on varied test results, and the risks, benefits and limitations of genetic testing.

References

1. Petersen GM: Genetic testing. Hematol Oncol Clin North Am 14 (4): 939-52, 2000.  [PUBMED Abstract]
   
   
2. Kuschel B, Lux MP, Goecke TO, et al.: Prevention and therapy for BRCA1/2 mutation carriers and women at high risk for breast and ovarian cancer. Eur J Cancer Prev 9 (3): 139-50, 2000.  [PUBMED Abstract]
   
   
3. Schoen RE: Families at risk for colorectal cancer: risk assessment and genetic testing. J Clin Gastroenterol 31 (2): 114-20, 2000.  [PUBMED Abstract]
   
   
4. Trepanier A, Ahrens M, McKinnon W, et al.: Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors. J Genet Couns 13 (2): 83-114, 2004.  [PUBMED Abstract]
   
   
5. Weitzel JN, Lagos VI, Cullinane CA, et al.: Limited family structure and BRCA gene mutation status in single cases of breast cancer. JAMA 297 (23): 2587-95, 2007.  [PUBMED Abstract]
   
   
6. Hampel H, Sweet K, Westman JA, et al.: Referral for cancer genetics consultation: a review and compilation of risk assessment criteria. J Med Genet 41 (2): 81-91, 2004.  [PUBMED Abstract]
   
   
7. Tobias DH, Eng C, McCurdy LD, et al.: Founder BRCA 1 and 2 mutations among a consecutive series of Ashkenazi Jewish ovarian cancer patients. Gynecol Oncol 78 (2): 148-51, 2000.  [PUBMED Abstract]
   
   
8. Beller U, Halle D, Catane R, et al.: High frequency of BRCA1 and BRCA2 germline mutations in Ashkenazi Jewish ovarian cancer patients, regardless of family history. Gynecol Oncol 67 (2): 123-6, 1997.  [PUBMED Abstract]
   
   
9. American Society of Clinical Oncology.: American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncol 21 (12): 2397-406, 2003.  [PUBMED Abstract]
   
   
10. Genetic Counseling as a Profession. Chicago, IL: National Society of Genetic Counselors, 2006 Also available online. ² Last accessed September 5, 2007. 
    
    

Glossary Terms

One of two major ancestral groups of Jewish individuals, comprised of those whose ancestors lived in Eastern Europe (Germany, Poland, Russia). The other group is designated Sephardic Jews and includes those whose ancestors lived in North Africa, the Middle East, and Spain. Most Jews living in the United States are Ashkenazi Jews. Also called Eastern European Jews.

Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).

The genetic relationships within a family combined with the medical history of individual family members. When represented in diagram form using standardized symbols and terminology, it is usually referred to as a pedigree or family tree. Also called family medical history.

A gene mutation observed with high frequency in a population founded by a small ancestral group that was once geographically or culturally isolated, and in which one or more of the founders was a carrier of the mutant gene.

A communication process that seeks to assist affected or at-risk individuals and families in understanding the natural history, disease risks, and mode of transmission of a genetic disorder; to facilitate informed consent for genetic testing when appropriate; to discuss options for risk management and family planning; and to provide for or refer individuals for psychosocial support as needed. The National Society of Genetic Counselors Task Force has also defined the term genetic counseling.

Increased likelihood or chance of developing a particular disease due to the presence of one or more gene mutations and/or a family history that indicates an increased risk of the disease. Also called genetic susceptibility.

A change in the usual DNA sequence at a particular gene locus. Mutations (including polymorphisms) can be harmful, beneficial, or neutral in their effect on cell function.

The quantitative or qualitative assessment of an individual’s risk of carrying a certain gene mutation, or developing a particular disorder, or of having a child with a certain disorder; sometimes done by using mathematical or statistical models incorporating such factors as personal health history, family medical history and ethnic background.

The frequency with which a test yields a true positive result among individuals who actually have the disease or the gene mutation in question. A test with high sensitivity has a low false-negative rate and thus does a good job of correctly identifying affected individuals.

The frequency with which a test yields a true negative result among individuals who do not have the disease or the gene mutation in question. A test with high specificity has a low false-positive rate and thus does a good job of correctly classifying unaffected individuals.