Genetic variant “associated” with aggressive as compared to indolent forms of prostate cancer

Another new article in the Proceedings of the National Academy of Sciences has suggested the possibility of major progress in the prostate cancer research field — but at least this time the media seem to have got the story right!

According to this new paper by Xu et al., a multi-institutional research group has been able to identify a specific genetic variant that is strongly “associated” with the occurrence of aggressive (as opposed to indolent) forms of prostate cancer.

By carefully studying genetic information from seven different human populations, they were able to look, specifically, at the genes expressed by 4,829 patients with aggressive forms of prostate cancer and 12,205 patients with less aggressive disease. Their analysis demonstrated that the frequency of expression of the TT genotype of the single nucleotide polymorphism or SNP known as “rs4054823” was consistently higher among patients with more aggressive compared with less aggressive disease — in every one of the seven populations studied. Furthermore, this difference in the frequency of expression was at its highest when the researchers compared data  from patients with high-grade, non-organ-confined disease to data from patients with low-grade, organ-confined disease.

The authors conclude, simply, that their study “demonstrates that inherited variants predisposing to aggressive but not indolent [prostate cancer] exist in the genome.” They go on to suggest that such genetic variants have potential as early markers for risk of aggressive prostate cancer, and should be evaluated for such potential.

As we have stated many times before, an “association” of this type is not proof positive that a specific genetic variation either causes prostate cancer or is necessarily predictive for clinically aggressive disease. There will be a great deal more work needed to demonstrate either of those possibilities … but this does seem to be the first published report of an association between a specific genetic variant and clinically aggressive prostate cancer. Dr Xu is quoted as saying that the “entire field has a long way to go.” This specific genetic variant apparently occurs in a part of the human genome where we have yet to identify the function  of any specific pieces of DNA. As Xu is again quoted as saying, “Our understanding of how the genome works is very limited.”

Media reports on this paper have also been published by HealthDay, by the AFP, and by the Press Association, the  Daily Mail, and the Telegraph in the UK.

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