Emerging Issues in Genetics Technology

Evaluation of Genomic Applications in Practice and Prevention Working Group

In an era of personalized medicine, the potential benefits and harms of genetic tests need to be rigorously scrutinized before they are used in clinical settings. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP ) Working Group provides an evidence-based mechanism to facilitate the evaluation of genetic tests that are transitioning from research to clinical and public health practice.

Launched in 2005, the EGAPP Working Group ― which provides an unbiased, transparent, and systematic process for evidence-based assessments ― was set up to develop recommendations based on the validity and utility of genetic tests. The group recently developed new approaches and optimized existing methods for collecting, analyzing, and grading evidence on analytic and clinical validity and clinical utility of genetic and genomic tests.

The evaluation of genomic applications in practice and prevention (EGAPP) initiative: methods of the EGAPP Working Group. Genetics Med 2009:11(1): http://journals.lww.com/geneticsinmedicine/Abstract/2009/01000/The_Evaluation_of_Genomic_Applications_in_Practice.2.aspx

For more information on the EGAPP working group itself: http://www.egappreviews.org/default.htm

New Gene Test for the Treatment of Breast Cancer

Breast cancer is the most common cancer among Canadian women. According to the Canadian Breast Cancer Foundation, approximately 22,700 women will be diagnosed with breast cancer in 2009, or one in every nine women.

Gene expression profiling that assesses the need for chemotherapy as an adjuvant to hormone therapy in women with early stage, node-negative breast cancer has recently been developed. While chemotherapy can reduce the risk of breast cancer recurrence by about 25%, treatment is associated with serious side effects and is very costly.

The genetic test is intended to determine the likelihood of breast cancers’ recurrence and the anticipated benefit of chemotherapy. If there is a low likelihood that cancer will recur, chemotherapy can be avoided. The results of this test, in conjunction with other clinical information and laboratory tests, is intended to help clinicians and patients make more informed decisions about treatment management.

Impact of gene expression profiling tests on breast cancer outcomes. AHRQ, 2008: http://www.ahrq.gov/Clinic/tp/brcgenetp.htm.

Recommendations from the EGAPP Working Group: can tumor gene expression profiling improve outcomes in patients with breast cancer? Genetics Med 2009:11(1):

http://www.egappreviews.org/docs/EGAPPWG-BrCaGEPRec.pdf.

Genetic Test for Future Risk of Blindness

Age-related macular degeneration (AMD) is the leading cause of visual impairment in Canada. It is a progressive retinal disease that, if left untreated, can lead to blindness. Early detection and treatment can significantly slow the progression of the disease.

A new genetic test has been produced that is designed to determine the risk of developing macular degeneration. It is believed that genetic inheritance plays an important role in the disease. The test will allow clinicians to diagnose AMD before symptoms are present.

Since there is currently no known cure for AMD, prevention is important. According to the Canadian National Institute for the Blind, lifestyle changes such as cigarette smoking, hypertension, overexposure in sunlight, and diet are modifiable factors that can play a role in reducing risk.

Genetic testing for macular degeneration. AMD Support Canada, 2008: http://www.amdsupport.ca/2008/07/23/genetic-testing-for-macular-degeneration/.

Predictive Gene Testing for Colon Cancer Treatment Options

A new genetic test, which scans for mutations in 12 genes expressed by colon tumours, has been developed for patients with stage II colon cancer. The test is designed to help predict which colon cancer patients are at a higher or lower risk of having their cancer return after surgery. Approximately 80% of stage II colon cancers are cured by surgery alone. However, there is no reliable way to predict who will require chemotherapy.

For patients in the low-risk group, the chance of recurrence three years post-surgery is believed to be approximately 8%. Patients in the high-risk group have a 21% chance of recurrence. Evidently, EGAPP believes “is currently insufficient to recommend for or against the routine use of UGT1A1 genotyping in patients with metastatic colorectal cancer who are to be treated with irinotecan”.

Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? Genetics Med 2009.

Type 2 Diabetes Gene Test

The detection of a gene variant that is almost twice as likely to be present in people with type 2 diabetes has paved the way toward the development of a genetic test for the prediction of type 2 diabetes.

The test identifies the presence of two copies of the transcription factor 7-like 2 or TCF7L2 gene. The results of a positive test are believed to be of particular relevance to pre-diabetics who could reduce their risk of developing type 2 diabetes through weight loss and/or medication use.

It is believed that the test’s ability to predict a patient’s genetic susceptibility to developing type 2 diabetes is currently no better than other predictors of risk.

Genotype score in addition to common risk factors for prediction of type 2 diabetes.  NEJM, 2008: http://content.nejm.org/cgi/content/short/359/21/2208.

New Genetic Test for Down Syndrome

Advances in pre-natal testing are intended to make the process of diagnosing certain fetal anomalies technically easier, safer, and available earlier in pregnancy.

A new genetic test could prevent the need for invasive procedures such as amniocentesis, which requires inserting a needle into the uterus and is associated with an elevated risk of miscarriage. The new test involves taking a sample of the mother’s blood, which contains DNA from the mother and her fetus. The test identifies genetic problems much earlier in gestation, around 12 weeks, than conventional tools.

The new method searches for abnormalities in the number of fetal chromosomes. Errors in chromosome numbers cause severe problems in physical and mental development. In addition to diagnosing Down Syndrome, this test also detects other chromosomal conditions, such as Edwards syndrome and Patau syndrome.

Current evidence using this technique is based on a small study of 18 pregnant women.  A follow-up study evaluating the test in a larger population is underway. 

A safer test for Down Syndrome: A noninvasive technique screens maternal blood for fetal DNA. Technology Review, 2008: http://www.technologyreview.com/biomedicine/21474/.

Genetic Predictors of IVF Success

A blood test is currently in development that could help in-vitro fertilization (IVF) decision-making.

Gene expression research has identified biomarkers in blood which can predict the likelihood of the successful implantation of an embryo. The gene analysis identified 128 genes that showed a more than two-fold difference in expression in early pregnancy compared with a non-pregnant state.

The research will also help to determine biomarkers that can identify events occurring at implantation, the maintenance of pregnancy, and a successful or unsuccessful pregnancy outcome.

The blood test could potentially spare couples the disappointment of repeated IVF failures and could save thousands of dollars in unnecessary IVF treatment.

Will IVF work for a particular patient? The answer may be found in her blood. Eurekalert, 2009: http://www.eurekalert.org/pub_releases/2009-07/esfh-wiw063009.php.

Suggested reading:

How will pharmacogenetics impact on pharmacy practice? Pharmacists’ views and educational priorities. NHS Evidence, 2008: http://www.geneticseducation.nhs.uk/downloads/Pharmacogenetics.pdf.

Pharmacoeconomic evaluations of pharmacogenetic and genomic screening programmes: a systematic review on content and adherence to guidelines. Pharmacoeconomics. 2008; 26(7):569-87.

The evaluation of clinical validity and clinical utility of genetic tests.  NHS Evidence, 2007: http://www.phgu.org.uk/file_gateway?link_ID=3932.

Genetic tests for cancer. AHRQ, 2006: http://www.ahrq.gov/clinic/ta/gentests/gentests.pdf.