Applying Genomics

Predicting Disease Risk at the Individual Level

Predicting disease risk involves screening currently healthy individuals by genome analysis at the individual level. Health care professionals can recommend intervention with lifestyle changes and drugs before disease onset. However, this approach is most applicable when the problem resides within a single gene defect. Such defects only account for approximately 5 percent of diseases in developed countries. Most of the common diseases, such as heart disease, are multi-factored or polygenic, which is a phenotypic characteristic that involves two or more genes, and also involve environmental factors such as diet. In April 2010, scientists at Stanford University published the genome analysis of a healthy individual (Stephen Quake, a scientist at Stanford University, who had his genome sequenced. The analysis predicted his propensity to acquire various diseases. The medical team performed a risk assessment to analyze Quake’s percentage of risk for 55 different medical conditions. The team found a rare genetic mutation, which showed him to be at risk for sudden heart attack. The results also predicted that Quake had a 23 percent risk of developing prostate cancer and a 1.4 percent risk of developing Alzheimer’s. The scientists used databases and several publications to analyze the genomic data. Even though genomic sequencing is becoming more affordable and analytical tools are becoming more reliable, researchers still must address ethical issues surrounding genomic analysis at a population level.

Art Connection

The PCA3 test occurs in three steps. In step one, PCA3 mRNA anneals to complementary DNA primers that are attached to beads. In step two, the mRNA is amplified using reverse-transcriptase PCR. In step three, the mRNA is detected using a chemiluminescent probe.
PCA3 is a gene that is expressed in prostate epithelial cells and overexpressed in cancerous cells. A high PCA3 concentration in urine is indicative of prostate cancer. The PCA3 test is a better indicator of cancer than the more well known PSA test, which measures the level of PSA (prostate-specific antigen) in the blood.

In 2011, the United States Preventative Services Task Force recommended against using the PSA test to screen healthy men for prostate cancer. Their recommendation is based on evidence that screening does not reduce the risk of death from prostate cancer. Prostate cancer often develops very slowly and does not cause problems, while the cancer treatment can have severe side effects. The PCA3 test is more accurate, but screening may still result in men who would not have been harmed by the cancer itself suffering side effects from treatment. What do you think? Should all healthy men receive prostate cancer screenings using the PCA3 or PSA test? Should people in general receive screenings to find out if they have a genetic risk for cancer or other diseases?