Surprise, Surprise, Genetic risks in Diabetes and Melanoma!

The Annals of Internal Medicine has a great article this week on genetic risks so does the ACMG Genetics in Medicine Journal for May.


The take home point is something which people may find interesting and it is something I feel is very real. I have begun to think that these Genomic tests act a lot like a placebo. They often don't add anything clinically. Hell, they may not even do anything to guide therapy (Pgx and high penetrance genes aside)


But they often act psychologically, either for good, or for bad.


First in the Annals of Internal Medicine; People have been arguing that perhaps testing only ONE snp and representing its risk is for disease is silly and in fact taht the REAL way to represent these risks is with a multiSNP panel. In Fact, this is what has been perhaps the selling point of some DTC genomics companies.


Even with this possibilty, the CDC and NIH are not satisfied with what the DTC companies are representing as risk.......Psychologically, that could be devastating to the would be consumer. Lack of public trust is a BIG DEAL......even in this era of lack of trust in everyone.


So let's look at what a multiSNP panel would do. The deCode/DNADirect T2 test looks at TCF7L2 (rs12255372), CDKAL1(rs7756992), PPARG( rs1801282),, CDKN2A(rs564398)





The Annals did a scientific study looking at these SNPs as well as loci including HHEX (rs1111875), IGF2BP2 (rs4402960), SLC30A8 (rs13266634), WFS1 (rs10010131), CDKN2A/B (rs564398, rs10811661) and KCNJ11 (rs5219).





What did they find?

The GRS significantly improved case–control discrimination beyond that afforded by conventional risk factors, but the magnitude of this improvement was marginal: Addition of the GRS increased the AUC by only 1%.






This is why I love science. The Journalists and Public read the word SIGNIFICANTLY different than I. In this case, statistical significance (which this word connotes) is essentially a useless guidepost. Becaue the enhanced effect was ONLY 1% better rates of prediction.....But my guess is that a crafty PR propaganda firm would USE the word Significantly in a far different way to manipulate the public.






Hence, placebo effect by hyped study results. The result? Buying more tests? Ask DeCode or DNADirect about that one.







But in this case if the results caused a patient to lose weight and exercise, that would be great. I am STILL waiting for that study.






It seems though as if the genetic risks gods have answered my request, at least with melanoma.

What if we could identify risk and the clinical or medical things we could do to prevent offered no benefit?






Hence the case with testing for Melanoma risk genes. Myriad said that Melaris testing would cause a patient to get more skin exams which would ultimately "reduce incidences and detect melanoma earlier." The data for that are not there to make any judgement on its ability to reduce disease.

But what about the psychological effects? Well, in an article to be published in May's edition of Geneitcs in Medicine it turns out that people with a family history of the skin cancer melanoma show reductions in anxiety and depression after getting tested for a high-risk gene mutation.

Over one hundred patients with a FAMILY HISTORY of melanoma were offered testing for CDKN2a, yes one of the diabetes genes.....







Myriad has this test and it is called Melaris. It turns out ONLY 25 got tested.....so this is not exactly what I call a very powerful study...nonetheless....patients who found they carried the high-risk gene had a significant reduction in scores for anxiety at two weeks after testing. Depression scores were also decreased, and remained so at one-year follow-up.






The Australians are particularly sensitive about Melanoma and it turns out it this case like to "feel" proactive.







Hence, Placebo effect, as we aren't sure if clinical exams prevent disease. But also perhaps some therapeusis if the begin to start wearing sunscreen. Something you hoped they would have done based merely on their family history...If the risk was ever conveyed to that member







The Sherpa Says: Placebo effect works, we know this in medicine. The real question is whether it is worth 99,000 USD.......or even 399?

No More Skin Biopsies????

Imagine going to your dermatologists office and instead of getting biopsied for your funny looking mole, the dermatologist places a little sticker on the mark.

He sends it off in the mail and later that week you are told that it is just a mole....phew......

That is the promise of a new technique called EGIR or epidermal genetic information retrieval. A new company called DermTech has just developed the technique. So what is the technique and how does it work?

The tape collects RNA from the skin sample. The sample then was amplified as cDNA and a microarray checked for the 117 gene analysis. This technique was studied and a 5 gene profile was adopted and accurately differentiated melanoma from benign skin changes. This technique is being evaluated at University of California San Francisco.

The Sherpa Says: In general only 3-10% of suspicious lesions are actually melanomas. The traditional method to detect includes a scalpel excision.....Tape......Scalpel... You decide. However, this is only a small study that determined proof of concept. There is a replication study underway and despite being great for the patient, the dermatologist can't exactly bill for RNA extraction. They do get paid very nicely for skin biopsies though. Not quite for prime time, but it does demonstrate how ubiquitous genetic soon will be in the office.

Minor Retraction

I would like to post a minor retraction. After spending time reviewing a certain Direct to Consumer genetic testing website, I found mention of:

1. That not all hemochromatosis is caused by HFE. It was one sentence in relation to several paragraphs on the page.
2. That you could test for iron studies, "Doctors usually perform screening tests before moving on to genetic testing or liver biopsy. " No, ALL doctors test iron levels prior to genetic testing or liver biopsy. It is the standard of care. You would get sued if you did not test iron studies first.
3. On their HFE questionnaire there is no place to state "no/yes my iron has been tested"

So... sorry for failing to mention that this info can be found approximately 5 clicks away from the testing info.

By the way, Myriad just released their 10Q for December Gross profits have tripled since 2004. Perhaps it is due to the "lab reps" they send into swanky offices in Greenwich and Park Avenue? Or maybe it is their gene patents, stifling innovation and research. Shame on you Dr Henderson