Is the chance of getting prostate cancer written in our DNA?
Worldwide Cancer Research funded scientists at the University of Turku in Finland have identified small variations in specific bits of DNA which cause men to have a higher chance of developing the most aggressive forms of prostate cancer. These latest findings are published online in the journal Genes Chromosomes Cancer.
Prostate cancer is now the most common cancer in the UK, and worldwide more than 1.11 million men were estimated to have been diagnosed with the disease in 2012. The exact causes are still unclear, although many factors that increase a man’s risk of it are now known and these latest findings add to this knowledge.
Using prostate cancer samples and blood tests from 41 men, Professor Johanna Schleutker and her team identified six sections of DNA, called single nucleotide polymorphims (SNPs), which can influence prostate cancer. SNPs (pronounced snips) are like a single typo in a book. Many don’t make any difference to the proteins they are the building instructions for, but other SNPs can have a huge impact. For example, if you were baking a cake and the instructions said fluur instead of flour, you would likely still know what it meant and it would be OK. But if the oven temperature said 100 degrees instead of 190 degrees, your cake would never bake and the result would be a gloopy mess.
The four newly identified SNPs, imaginatively named rs143975731, rs12277366, rs2155225 and rs2155222, were all found to regulate the DGAT2 gene, already known to be involved in prostate cancer.
The SNPs were pinpointed to the chromosomal region 11q13.5 where they sit in something called a ‘non-coding region.’ This means they don’t form part of any building instructions for making proteins, but instead may have a regulatory effect on other genes that do make proteins.
From a previous large scale study in Finnish men, Professor Schleutker knew the region 11q13.5 had a role in prostate cancer but until now the exact details were unclear.
She explained “A man’s genetic predisposition (the genes that are able to influence his risk of getting a disease) to prostate cancer has been widely studied, and more than 100 sections of DNA (known as loci) have been identified.
Here we studied the loci at 11q13.5 and the impact on gene expression (when genes are switched on to make proteins) in men with and without prostate cancer from families where other members also had the disease. The results were then confirmed in another set of tumours and in blood-derived cell lines called LCLs.”
Interestingly, two other SNPs the team identified, rs72944758 and rs1089921, were reported to associate inversely with prostate cancer risk. This means that if men have these SNPs they may be less likely to get the disease but if they do get prostate cancer, they are more likely to die from it. These SNPs were found to regulate CAPN5 and AP001189 genes, also found in this study to be involved in prostate cancer.
Knowledge of the four new SNPs associated with an increased risk of developing the disease could be further developed into a test to identify men who are more at risk of getting prostate cancer, so they could be monitored more closely. This is especially important for men who develop the more aggressive form of the disease, who also tend to be younger, and for whom early treatment is more urgent.
The two SNPs that are linked to poorer patient outcomes could potentially be developed into a prognostic test to help identify men who are less likely to have success with treatment.
This work was also supported by: the Sigrid Juselius Foundation, the Cancer Society of Finland, the Finnish Academy, the Medical Research Fund of Tampere University Hospital (X51003), the Emil Aaltonen Foundation, the Ida Montin Foundation, the Maud Kuistila Memorial Foundation and the Finnish Cultural Foundation.