As I approach the age at which the word ‘prostate’ starts sounding like a funereal drum, I become more interested in studies such as those published this week in the NEJM and about three weeks ago in Nature Genetics.
The NEJM paper, by Lilly Zheng and colleagues, shows that single-nucleotide polymorphisms (SNPs) in five chromosomal regions, each of which had previously and independently been associated with prostate cancer, have a cumulative association with the disease when considered in combination. The authors estimate that the five SNPs and a family history of prostate cancer account for as many as 46% of the cases in the Swedish population they studied.
The three Nature Genetics papers, by Julius Gudmundsson et al., Gilles Thomas et al. and Rosalind Eeles et al., all of which are nicely summarized in the journal’s March editorial, disclose multiple new susceptibility loci associated with prostate cancer that, together with other loci identified in 2006 and 2007, give us plenty of new avenues to explore in order to understand the disease.
The most immediate implication of findings of this sort is often diagnostic — if you identify gene variants that are linked to a disease, you can ask questions about how good these variants are at predicting onset and/or progression of the pathology. Validating the diagnostic value of these genomic data often requires blinded samples analyzed in a prospective (preferably longitudinal) fashion.
The findings could also help us understand the biology of the disease, although this almost always takes more time and is not always pursued, as it is very challenging: you need to identify with precision the protein whose gene harbors the relevant SNP, then establish how the SNP affects protein function, and finally look at how this altered function modifies the physiology of the cell as it becomes tumorigenic in an in vivo setting.
This is what we at Nature Medicine look for when we evaluate submissions that report new associations of SNPs or mutations with disease, which is why we don’t tend to publish too many of these kind of studies. That said, these ruminations do not take anything from the value of these four studies, which shine some more light on the black box that prostate cancer has turned out to be.