What PAs should know before they refer patients to a genetic counselor

DISCUSSION

When to refer a patient to a genetic counselor can depend on many factors: a clinician's understanding of the disease, the resources accessible to the clinician, and the geographic accessibility of a geneticist or genetic counselor.

Access to a professional with the ability to appropriately interpret and communicate the results of tests and to prospectively advise the patient on the implications (medical, psychosocial, and financial) is a particularly important consideration. Appropriate interpretation may seem like a no-brainer; after all, the laboratory provides an interpretation. However, many genes can cause the same disease, and a single genetic test may capture only a small percentage of cases, so negative results may not rule out risk for the condition. An adequate understanding of the detection rate, what percentage of cases is captured by a genetic test, and what a positive or a negative result can mean (ie, whether the result rules out the diagnosis or does not rule out the diagnosis) is essential.

Medical practice often requires the clinician to convey life-altering information, such as a diagnosis of cancer or the identification of a birth defect on prenatal ultrasound. Hereditary conditions create unique circumstances, however, in which anticipatory guidance about the implications of the results is often needed. Sometimes patients learn about their risk of a genetic predisposition prior to experiencing any symptoms. They may learn about a risk to their children. Or they may learn about potential future medical complications (for example, the risk of aortic aneurysm in someone with Marfan syndrome). In such cases, the clinician's role is to ensure that patients understand the magni tude of the information they would receive from genetic testing, that they actually want that information, and that they are prepared to deal with it, regardless of the treatment options (or lack thereof), all before the test is even ordered. We often worry most about people who want presymptomatic testing for devastating neurodegenerative conditions, such as Huntington's disease, but there can be enormous psychological pressure associated with learning genetic test results after the patient is symptomatic, as illustrated by the case presented.

Ultimately, no concrete list of circumstances can guide a clinician to decide when to refer and no magical powers are possessed by geneticists and genetic counselors. The process is similar to deciding to refer to any other specialist, and it can be guided by some simple questions: Are you equipped (with knowledge, resources, colleagues) to give this patient the best care as it relates to this situation? Are you prepared to discuss the implications of being tested? Will you subsequently be able to interpret the results? JAAPA

Erynn Gordon is director of genetic counseling at the Coriell Institute for Medical Research in Camden, NJ. The author has indicated no relationships to disclose relating to the content of this article.

REFERENCES

1. King M-C, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302(5645):643-646.

2. Antoniou A, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72(5):1117-1130.

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Follow-up to genetic assessment in determining disease risk

Erynn Gordon, MS, CGG; Michael Rackover, PA-C, MS

In an earlier article, “The role of genetic assessment in determining a patient's disease risk” (“Genomics in PA Practice,” May 2009), we presented a patient's genetic pedigree and the results of his genetic testing and asked readers how they would counsel him. Even without the genetic test results, several findings in the patient's family history were noteworthy. First, the combination of pancreatic cancer and breast cancer in a family of Ashkenazi Jewish descent suggests the possibility of a BRCA1 or BRCA2 gene mutation. Although BRCA1 and BRCA2 are most often associated with an increased risk of breast and ovarian cancer, there is also an association with other cancers, including prostate cancer; melanoma; and pancreatic cancer, with one study finding BRCA mutations in 5.5% of Ashkenazi Jewish patients with pancreatic adenocarcinoma.1 This finding, in combination with a higher rate of BRCA1 and BRCA2 mutations (three common mutations) in the Ashkenazi Jewish population, makes this history worth investigating further. In addition, the paternal family history of acute MI, pulmonary embolism, and deep venous thrombosis raises questions about a hereditary cardiovascular risk factor. However, given the variety of ages at onset, some of which were late in life, further investigation of other cardiovascular risk factors, such as weight, smoking status, and various comorbidities, is also warranted. Finally, one cannot ignore the fact that multiple family members were reported to be infertile. If desired, a fertility workup should be considered.

The additional information provided by genetic testing adds another dimension to this patient's risk assessment. While the family history of glaucoma alone is not concerning (one second-degree relative affected), testing showed that the patient is homozygous for the LOXL1 gene, which raises his risk of glaucoma to 3.4% (triple the average population risk of 1.1%). The family history combined with the genetic test result suggests that the patient is at increased risk for glaucoma and warrants a referral for glaucoma screening. Note, however, that based on the genetic factors alone, he has a 96.6% chance of not developing glaucoma and should be following screening schedules based on national recommendations issued by such organizations as the American Academy of Ophthalmology and the American Optometric Association.

Finally, we must consider the patient's doubled risk for prostate cancer based on his having six of eight genetic risk markers. This risk is significant, and referral to a urologist is appropriate. We must be careful to avoid putting undue emphasis on these risk factors, however, as the four genetic variants studied (we all have two copies of each gene, yielding eight potential risk markers) represent only a portion of the genetic risk for prostate cancer. Heritability studies show that 42% of the risk for prostate cancer is genetic (of which these eight genetic risk factors represent only a portion) and 58% of the risk is environmental.2 Presently, the greatest known risks for prostate cancer are race (African-Americans are at highest risk) and family history. 3 Bringing the patient's family history back into focus, recall that BRCA2 founder mutations in the Ashkenazi Jewish population have also been associated with an increased risk of prostate cancer.4 Although mutations in BRCA2 were not included in this patient's genetic testing, the results have brought the important issues of his family history and genetics to the forefront and could be the catalyst for additional testing.

REFERENCES

1. Ferrone CR, Levine DA, Tang LH, et al. BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. J Clin Oncol. 2009;27(3):433-438.

2. Lichtenstein P, Holm NV, Verkasalo PK, et al. Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000;343(2):78-85.

3. Giovannucci E, Liu Y, Platz EA, et al. Risk factors for prostate cancer incidence and progression in the health professions follow-up study. Int J Cancer. 2007;121(7):1571-1578.

4. Agalliu I, Gern R, Leanza S, Burk RD. Associations of high-grade prostate cancer with BRCA1 and BRCA2Clin Cancer Res. 2009;15(3):1112-1120. founder mutations.