Data from a multinational study has identified 22 genetic variations that appear to be associated with an increased risk of developing prostate cancer. The findings, which were published in Cancer Discovery, are based on a large-scale analysis of genetic variants within putative miRNA binding sites in prostate cancer.1
The investigators report that genome-wide association studies have identified 100 risk variants for prostate cancer. However, those 100 risk variants only explain approximately 33% of the familial risk of the disease.
The researchers hypothesized that a comprehensive analysis of genetic variations found within the three untranslated regions of genes predicted the effect of miRNA binding (miRSNP), further identifying additional prostate cancer risk variants.
The researchers investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 prostate cancer cases and 22,320 controls of European ancestry from 23 participating studies.
This analysis was part of the PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) consortium whose goal is to identify genetic risk factors associated with prostate cancer. The researchers found that 22 miRSNPs were associated with risk of prostate cancer.
Importantly, seven of the variants could differentiate between aggressive and nonaggressive disease.
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The researchers further confirmed the importance of two of these genetic variants by investigating how they influence protein expression in normal and cancerous prostate tissue.
They discovered that one of the variants plays an important role in mediating expression of the prostate serum marker prostate specific antigen (PSA), and the second variant controls expression of a gene involved in metabolism.