What is deCODE ProstateCancer™?
Prostate cancer is the most commonly diagnosed non-skin cancer in men in developed countries and the second leading cause of cancer death, after lung cancer, among men in the United States. It carries a lifetime risk of 16% and a mortality of 3% in the general population. The risk is generally higher for men of African-American heritage, for men with affected fathers and/or brothers, and for those with relatives diagnosed at younger ages. A family history of breast or ovarian cancer can also be a risk factor, as the diseases can share common genetic mutations.
Almost 95 percent of prostate cancers are adenocarcinomas, most grow slowly, improving the chances of early detection, diagnosis, treatment and survivability. Early detection is key to overcoming prostate cancer; the five-year survival rate among men whose prostate cancer is caught early is 100 percent.
The deCODE ProstateCancer ™ test is a novel, non-invasive, DNA-based reference laboratory test for the first genetic risk factors ever found to confer risk for a common type of cancer in the general population. These markers are not dependent on a family history of prostate cancer – in fact, they are independent of family history and the genetic risk of the ProstateCancer test multiples with the family risks mentioned above. All but one of the variants were discovered in Iceland and confirmed in several American and European ancestry cohorts but have also been confirmed in several other populations by independent research groups.
The deCODE ProstateCancer ™ test identifies eight known variants, three on chromosome 8 (in the 8q24 region), two on chromosome 17 (in regions 17q12 and 17q24.3), one on chromosome 2 (in the 2p15 region), one on chromosome 11 (the 11q13.3 region) and one on the X-chromosome (sex chromosome; Xp11.22) . Based on the presumption that these markers are independent, and the individual risks therefore multiply, the various genotype combinations have associated relative risks in the range of 0.33(non carriers for any of the risk markers) to 17.6 (homozygous for all of the eight risk variants) compared to the general population risk. Combined, these 8 variants appear to account for about half of the cases of prostate cancer (sometimes termed population attributable risk). About 40% of the population has a genotype combination of the tested markers that have an increased relative risk (>1) over the general population and about 10% of the population has a genotype combinations that confer an average two-fold relative risk and about 1% have relative risk above 3. One should be careful to apply extreme risk results to individuals since they are based on presumptions of a multiplicative model and are associated with genotype combinations that are extremely rare.
The risk distribution in the general population, i.e. the proportion of the population that will have a lower/higher relative genetic risk than any given relative risk-result of the test.
Genetic risk distribution by deCODE ProstateCancer™ genotype results.
The results of the deCODE ProstateCancer are reported as the combined genetic risk associated with the individual’s genotype combination and as an individual lifetime risk compared to the population lifetime risk. A graph such as the one above will be provided that allows the individual’s risk results to be compared to risk and genotype distribution of the general population (see sample report on the “Result and report” web page). Note that deCODE ProstateCancer™ only measures these 8 validated genes. There are likely other genes that have not yet been discovered and there are other risk factors such as family history and ethnicity that need to be multiplied to this genetic risk to refine an individual’s risk.
The deCODE ProstateCancer™ test is performed in deCODE’s CLIA-registered laboratory. The test can only be ordered by qualified physicians and medical practitioners. If you are an individual interested in deCODE ProstateCancer™, you can continue reviewing this site, and even download and print the test order forms to meet with your doctor and discuss the next steps.
Certain genotype combinations of two of the SNPs included in the deCODEme ProstateCancer™ test (rs2710646 and rs1447295) predict a more aggressive and advanced form of the cancer at the time of diagnosis. Aggressiveness of prostate cancer is traditionally classified according to the TNM scoring system and histological grade based on the Gleason score. Being homozygous for the risk alleles (AA) at either or both of the aforementioned SNPs or being heterozygous (A) for the risk alleles at both loci or even only rs1447295, carries an increased relative risk of 1.1 to 1.58 for a T-score of 3-4 and/or N+ and/or M+ and/or Gleason score of 7-10. In general about 40% of all prostate cancers are of these grades at the time of diagnosis.
Read more: Genetic risk of Prostate cancer>>