Am Fam Physician. 2004 Nov 1;70(9):1637-1642.
The dawning of the genome era is changing the scope of care for family physicians, with significant implications for the design of future health care delivery systems. Many consider the imminent introduction of genomics into clinical medicine to be the most significant advance in health care since antibiotics were introduced. Being able to build on the strengths of the physician-patient-family relationship enhances the potential for family physicians to realize the benefits of genomic technology. Knowledge of the individual patient across his or her lifespan provides an excellent foundation from which to begin integrating genomics information to improve health outcomes.
For example, a 43-year-old woman is concerned about her possible risk of cancer. She has been your patient for many years. You also cared for her mother before she was diagnosed with colon cancer at age 49. The patient reveals that her 45-year-old sister was diagnosed recently with colon cancer. Recognizing that a two-generation family history of colon cancer at a young age may indicate that your patient is at increased risk of developing colorectal cancer (http://www.cancer.gov), you gather more family history and consider the possibility of hereditary nonpolyposis colorectal cancer (HNPCC).1 Based on U.S. Preventive Services Task Force guidelines,2 you recommend a colonoscopy. Recognizing the potential implications of this information for your patient and her family, you ask if she is interested in learning more about genetic counseling and genetic testing for HNPCC. Ultimately, the patient and her sister test positive for a mutation in the MLH1 gene. Your patient is found to have three small polyps, which are excised. She agrees to a program of an annual colonoscopy that has an excellent chance of keeping her healthy.
This type of diagnostic testing, coupled with counseling and carefully designed programs of individualized prevention, will be feasible for an increasing number of common diseases in the next decade. The opportunity to integrate genomic biologic, clinical, and behavioral tools into your current scope of practice can make a difference in the care of patients whom you already are seeing.
Another application of genomics that will be increasingly common in family practice is pharmacogenomics. Variability in drug response can be a vexing problem, and often may be caused by genetic differences in individual patients, either with regard to drug metabolism or the targeted pathway.3,4 The objective of pharmacogenomics based on a patient’s molecular genomic profile is to predict responsiveness to treatment, and then to improve results. This improvement in outcomes can occur only with sufficient understanding and appropriate use of genetically based testing in clinical practice.
In another example, a male patient and his wife come to you with some questions. Recently diagnosed with lung cancer, he has heard about a new drug called gefitinib. His female cousin died last year from lung cancer following treatment with that same drug. He and his wife wonder if it would be worth going through the chemotherapy. You are aware of a research study in which patients with certain somatic mutations in the epidermal growth-factor–receptor gene of the lung cancer tissue responded well to gefitinib. This molecular information was helpful in predicting improved clinical response and selecting those patients who would benefit from this specific drug intervention.5,6 You explain to your patient and his wife why he may respond differently than his cousin did to the treatment, and then make arrangements for DNA testing of his tumor specimen.
It also is likely that genomics will be the driving force behind new therapeutics during the next few decades. The molecular information about disease pathology generated by the genomics approach provides the opportunity for truly rational drug development. Such drug development is happening already in the oncology field, with the development of imatinib7 and gefitinib. The same type of drug development can be expected to happen in a few years for diseases such as diabetes, Alzheimer’s disease, and osteoporosis. Options of care eventually will include genomic information along the pathway for care of all diseases, including prevention, screening, diagnostics, prognostics, selection of treatment, and monitoring of treatment effectiveness.
The rate of progress for applying a genomic approach throughout the continuum of care depends not only on technologic advances but also on physician expertise. The complexity of adopting this knowledge into practice includes an awareness of the science, provision of explanations to ensure informed patient decision making, and evaluation of the physical and psychologic ramifications of those decisions. Use of genomic information to meet the needs of patients in a changing health care environment requires a focus on reimbursement issues, informed resource access, and evaluation of the family practice environment to ensure confidentiality of collected genetic information (http://www.aafp.org/x24762.xml). Many of these topics will be highlighted in the monthly Web-based modules available through the American Academy of Family Physicians’ (AAFP’s) 2005 Annual Clinical Focus on genomics.
Genomic medicine is evolving rapidly. Even greater promise exists for the future. We do not yet have all the answers. A particularly important challenge is identifying the interaction of genes with other factors, such as environment and behavioral choices.8 Ongoing research will provide much needed data that will assist in translation into practice. However, translation of genomic research discoveries to improved clinical outcomes can occur only with an informed professional workforce. An informed family physician can be an active contributor to the design of future health care services, systems, tools, and resources that integrate genomic information. As genomic scientific knowledge rapidly advances, family physicians can assume a proactive role in learning about and realizing the potential of genomics in clinical care. Integration of genomics into medical curricula already has been recommended for family practice residents (http://www.aafp.org/x16547.xml). The AAFP, through the initiation of the Genomics Year in 2005, has made a statement about the importance of genomics competency for family physicians. Realizing the potential value of genomics in clinical care will be enhanced greatly through this educational effort.
Francis Collins, M.D., Ph.D., is the director of the National Human Genome Research Institute at the National Institutes of Health, Washington, D.C.
Address correspondence to Jean Jenkins, Ph.D., R.N., National Human Genome Research Institute, National Institutes of Health, 31 Center Dr., Bldg. 31 4B09, Bethesda, MD 20892-2152 (e-mail: email@example.com). Reprints are not available from the author.
1. Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003;348:919–32.
2. U.S. Preventive Services Task Force. Screening for colorectal cancer: recommendations and rationale. Rockville, Md.: Agency for Healthcare Research and Quality, July 2002. Accessed online July 2004 at: http://www.ahrq.gov/clinic/3rduspstf/colorectal/colorr.htm.
3. Evans WE, McLeod HL. Pharmacogenomics—drug disposition, drug targets, and side effects. N Engl J Med. 2003;348:538–49.
4. Green MR. Targeting targeted therapy N Engl J Med. 2004;350:2191–3.
5. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–39.
6. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–500.
7. Wong S, Witte ON. The BCR-ABL story: bench to bedside and back. Annu Rev Immunol. 2004;22:247–306.
8. Collins FS. The case for a U.S. prospective cohort study of genes and environment. Nature. 2004;429:475–7.
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