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The Human Genome

The Human Genome Project and Women's Health

Heather M. McManus, MS; Elizabeth M. McNally, MD, PhD

The first draft of the human genome was completed in February 2001. With this monumental accomplishment, the era of genetics is evolving rapidly and will change women's health and the manner in which it is provided. In the past, physicians have used genetic technology to identify pregnancies at risk of inherited disease. Our understanding of inheritance and disease susceptibility is growing, and the utility of genetics is now expanding to adult-onset diseases. It is now known that genetic factors contribute to nearly every common disease and by the year 2010, it is estimated that genetic testing will be available for as many as 10 common diseases.¹ Because the primary physician usually serves as the entrée for a patient's genetic inquiries,² the need to help primary physicians and patients learn about the genetics of common diseases is ever-intensifying.

Currently, genetic testing is available for 564 diseases.³ Although many of these diseases are rare (incidence of 1/1000 to 1/10,000), clinical genetic testing for some common diseases is already available. Genetic testing for diseases such as cystic fibrosis, thalassemia, Duchenne muscular dystrophy, and hemochromatosis are already available. Over the past 7 years, genetic testing for autosomal dominant breast and ovarian cancer has become increasingly available. Because mutation screening is costly and time-consuming, only women with a strong family history of breast and ovarian cancer are currently undergoing this testing. It is estimated that 203,500 American women will be diagnosed with breast cancer this year and 23,300 with ovarian cancer.⁴ Because 5% to 10% of these cancers are thought to be inherited, genetic counseling and testing can potentially benefit a large number of women in the United States. While taking on the role of genetic counselor and providing genetic testing may not be feasible for many physicians, identifying women at risk for genetic diseases is less difficult. A simple but thorough family history can identify women at risk for an inherited susceptibility to cancer. The following characteristics should be sought in a patient's family history, and if found, should signal the need for referral to a cancer genetic counselor or physician trained in cancer genetics.

• Cancer diagnosed at an early age (younger than age 50 years)
• Multiple family members (blood relatives) affected with cancer
• Other related cancers (breast/ ovarian or colon/uterine)
• Bilateral or multiple primary tumors
• Rare tumor types (example: male breast cancer)

In the coming years, genetic tests for coronary artery disease, hypertension, diabetes, and asthma are expected to be available. The public health benefits of identifying individuals at risk of developing an inherited genetic disease cannot be underestimated and need not wait for the availability of genetic testing. The same parameters that identify familial cancer risk (ie, earlier than general population age of onset, multiple affected family members, multiple affected generations) can be used to identify those patients at risk for other inherited diseases. A family history may lead to early detection and prevention of some common adult-onset diseases.

For example, coronary artery disease in a first-degree female relative younger than 65 years of age may signal increased risk for early-onset coronary artery disease. The following characteristics can be used as a guide for identifying patients at risk for coronary artery disease.

• Many family members affected, especially female relatives
• Early onset: men younger than 55 years of age, women younger than 65 years of age
• Multivessel disease
• Multiple risk factors
• Refractory to conventional therapy
• Family history of related conditions (ie, stroke, diabetes, hypertension, cholesterol abnormalities).

In the future, risk stratification for early onset coronary artery disease will utilize genetic testing. Currently, further risk stratification for early-onset atherosclerotic disease relies on lipid profiles. Patients should have a lipid panel performed to discover if they have high low density lipoprotein, low high density lipoprotein, high triglycerides, or high lipoprotein(a) (Lp(a)), as well as testing for clotting factors such as factor S, C and factor V Leiden. Patients identified as high risk can begin modifying other risk factors like weight, diet, exposure to cigarettes, and activity level in combination with drug therapy to reduce risk of heart disease. In addition, if a woman is discovered to have a lipid or clotting factor defect, she should be counseled that her children are also at risk and should be screened by a lipid panel to reduce the risk of heart disease in the next generation.

In familial cardiovascular conditions such as cardiomyopathies and arrhythmia syndromes, genetic testing is still in the research phase. This is not to say that individuals with a family history of cardiomyopathy and/or an arrhythmia syndrome cannot benefit from genetics. Individuals with inherited heart disease benefit from genetic counseling because this may help identify other related individuals at risk for heart disease and sudden cardiac death. Patients with a family history of heart disease involving sudden cardiac death and/or enlarged heart should be referred to a cardiologist for an electrocardiogram, echocardiogram, and Holter monitor to look for early signs and symptoms of the disease. The following characteristics can be used as a guide for identifying patients at risk for familial cardiomyopathy.

• Family members with an enlarged heart
• History of people dying young or suddenly
• Individuals with fast heart rate or palpitations
• Fainting episodes
• Ethnicity (example: arrhythmogenic right ventricular dysplasia may be more common in some populations).

The following characteristics can be used as a guide for identifying patients at risk for familial arrhythmia syndromes.

• History of people dying young or suddenly
• Personal or family history of fainting episodes or dizziness
• Personal or family history of irregular heartbeat
• Family history of death while swimming or other sudden unexplained accidents (example: unexplained automobile accidents)
• Family history of children dying as infants from Sudden Infant Death Syndrome (SIDS).

Once patients are identified as being at risk for developing a genetic disease, the next step is referral to specialists who provide accurate risk assessment and appropriate testing. While genetic professionals are increasing in number, many institutions do not have a genetic professional on staff. The National Society of Genetic Counselors provides a resource link for finding a genetic professional in your area. In addition, Online Mendelian Inheritance of Man (OMIM) provides up-to-date information on genetic diseases. Finally, GeneTests provides both comprehensive summaries of diseases for which genetic testing is available and how it can be obtained.

References

1. Collins F, McKusick V. Implications of the Human Genome Project for Medical Science. JAMA. 2001;285: 540-544.
2. American Medical Association. 1998 March. Home page. www.ama-assn.org/ama/pub/print/article/2398-2937.html Accessed 2001 Jan 17.
3. GeneTests<sum>GeneClinics: Genetics Information Resource. University of Washington and Children's Health Care System, Seattle, 1995. Available at www.genetests.org or www.geneclinics.org. Accessed 2002 May 28.
4. American Cancer Society. 2001 American Cancer Society home page. www3.cancer.org/cancerinfo. Accessed 2002 May 28.
   

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