EU-funded scientists say more accurate prostate cancer test in the pipeline
Scientists partially funded under the EU's Seventh Framework Programme (FP7) have identified human DNA (deoxyribonucleic acid) variants that enhance the predictive power of a test used to measure prostate specific antigen (PSA), a protein produced by normal prostate cells that is elevated when cancer is present. The results are presented in the journal Science Translational Medicine. The study, led by the Icelandic group deCODE Genetics, was backed by two EU-funded projects: PROMARK ('Genetic prostate cancer variants as biomarkers of disease progression') and CANCERGENE('Identification and functional characterisation of genetic cancer risk variants'). PROMARK has received EUR 2.71 million under the FP7 Health Theme and CANCER-GENE has clinched a Marie Curie Actions grant worth EUR 1.5 million. In general, practitioners test PSA levels to help them determine whether a patient is suffering from prostate cancer. Experts will suggest that a prostate biopsy should be performed in men with PSA levels above a certain threshold. The problem, however, is that cancer-free patients may have elevated PSA levels. It should be noted that there are considerable differences in the baseline healthy levels. This means that there are cases of men with cancer not being tested, while biopsies are carried out on healthy men. The researchers from Europe and the US analysed four single-nucleotide polymorphisms (SNPs) and discovered they can be used to derive a personalised PSA threshold that provides accurate information about which men are more likely to have a positive biopsy, and which patients do not need a biopsy. According to their findings, inherited factors play a role in some 40% of the variability of PSA levels in the general population. So adjusting test results for genetic effects could potentially enhance sensitivity and specificity. The team conducted the genome-wide association study and follow-up analysis using PSA data from 16,211 men (15,757 Icelandic and 454 British) - not diagnosed with prostate cancer - to determine sequence variants linked with PSA levels. They detected a genome-wide link between PSA levels and SNPs at six loci. The over 300,000 SNPs were then assessed in large case-control cohorts from Iceland, the Netherlands, Romania, Spain and the US to determine whether a link exists between PSA levels independent of risk of prostate cancer itself. They found that 3 alleles associated with elevated PSA levels were linked with higher probability of a negative biopsy for 3,834 men who underwent a biopsy. When analysing the link between the 6 loci and prostate cancer risk in 5,325 cases and the 41,417 controls, the researchers found that SNPs at 2 alleles were exclusively associated with PSA levels, while the other 4 loci were linked to prostate cancer risk. 'This is straightforward genetics with direct clinical utility,' explains deCODE Genetics chief Kari Stefansson, a senior author on the study. 'Detected early, prostate cancer can be treated with near total success. The challenge is to more effectively risk stratify the population, identifying and biopsying those at high risk and with aggressive disease while minimising the number of negative biopsies we perform,' he adds. 'And using the genetics we are improving the sensitivity and specificity of PSA testing. Like virtually every protein in the body, PSA levels vary between individuals according to SNPs that regulate gene expression. The SNPs reported today enable us to personalise PSA thresholds, thereby changing the recommendation on whether to biopsy for a substantial proportion of men.' Researchers from Iceland, the Netherlands, Romania, Spain, the UK and the US contributed to this study.
Countries
Spain, Iceland, Netherlands, Romania, United Kingdom, United States