The other day I clicked on a link someone shared on Twitter about new findings in breast cancer genes, which sounded really cool and interesting.  On clicking through it turned out to be a rather disappointing Reuters release on several fronts:

1. Where's the link to the original article (in these days of social sharing leaving it out is plain lazy)?
2. What/where are the "five common genetic factors" exactly?  No mention is made of them.
3. What does this finding actually mean?
4. What's the 'wow' factor here rather than the 'so what' factor?
   

I don't know about anyone else, but daily press releases and assaults in the media about identification of yet more gene blah blah that may or may not be relevant becomes anaesthetising after a while.

After a while, I finally tracked down the actual article in Nature Genetics myself to see what the data actually said (reference below with link to the paper for those interested).

What the researchers did was interesting; they conducted a large genome-wide study (GWAS) in around 8,000 people, approx. half of whom had a family history of breast cancer and half did not (controls). They then studied the DNA of another 24,000 women, with and without breast cancer.  By analysing over half a million SNP's, they were able to identify new 5 loci on chromosomes 9, 10 and 11 which if present, represent an increased risk of developing breast cancer.  This is in addition to 13 gene variations already identified in previous research.

Many of you will be aware of two high risk genes which are more likely to be defective in someone with breast cancer, known as BRCA1 and BRCA2.  These genes often confer higher risk of breast or ovarian cancers and can be tracked in families to try and pick up the cancer earlier. More recently, they have become targets for therapeutic intervention with PARP inhibitors such as AstraZeneca's olaparib in BRCA-positive breast and ovarian cancers.  More on this in another post. 

But what if these 5 new gene variations are also important and early identifiers of increased risk?

The reason that these findings are important is that as Prof Bert Vogelstein of Johns Hopkins never tires of pointing out at AACR meetings, most cancers, including breast cancer, are often diagnosed relatively late in their development and people die from the last 3 years of metastatic disease because the cancer went undetected for 20 odd years. 

GWAS as a field is also becoming more relevant, highlighting distinct subsets of
patients who can then be evaluated for prognosis, biomarkers, efficacy
and tolerability differences.

We still have very few methods of efficient and effective early detection, but what GWAS may allow us to do in future when we have more complete information (and gene testing is cheap, reliable and more widely available) is to potentially run screens to identify those most at risk for cancer.  These people could then be monitored more closely and watched diligently for early signs of cancer appearing.  Early stage cancer is potentially curable with surgery.  Inevitably, preventative studies could also be considered for high risk groups in future.

So these findings will have little immediate impact now, but in future if replicated, they could form the backbone of a comprehensive strategy to identify those people most at risk from developing cancer.  If we think about it, the enormous cost of end of life medical care massively dwarfs what the cost of earlier intervention and potential cure via surgery with or without neoadjuvant therapy would be.  Ultimately, we need this kind of data to move to a wellness model rather than a palliative model.

I would like to acknowledge my buddy Scott Hensley at NPR Health for prodding me into explaining the rationale behind my grump on Twitter about the flood of 'so what' rather than 'oh wow' gene data that constantly abounds daily.  If you're not following him on Twitter or listening to his awesome NPR Health podcasts on iTunes or the web, you should consider it!

Turnbull, C., Ahmed, S., Morrison, J., Pernet, D., Renwick, A., Maranian, M., Seal, S., Ghoussaini, M., Hines, S., Healey, C., Hughes, D., Warren-Perry, M., Tapper, W., Eccles, D., Evans, D., Hooning, M., Schutte, M., van den Ouweland, A., Houlston, R., Ross, G., Langford, C., Pharoah, P., Stratton, M., Dunning, A., Rahman, N., & Easton, D. (2010). Genome-wide association study identifies five new breast cancer susceptibility loci Nature Genetics DOI: 10.1038/ng.586