September is Now Ovarian Cancer Month

In one fell swoop of the pen on the 26th. President Bush signed into proclamation, September is now Officially Ovarian Cancer Month. This is a very big deal for those families who have been affected by an Ovarian Cancer diagnosis.

Some facts

Ovarian cancer is the most common cause of cancer death from gynecologic tumors in the United States. Early disease causes minimal, nonspecific, or no symptoms. Therefore, most patients are diagnosed in an advanced stage. Overall, prognosis for these patients remains poor. Standard treatment involves aggressive debulking surgery followed by chemotherapy.

Approximately 22,430 new cases of ovarian cancer are diagnosed annually.

Overall, the prognosis of ovarian cancer remains poor, with a 45% 5-year survival rate. Approximately 15,280 women die every year in the United States from ovarian cancer.

Parity is an important risk factor. Women who have been pregnant have a 50% decreased risk for developing ovarian cancer compared to nulliparous women. Multiple pregnancies offer an increasingly protective effect.

The lifetime risk for developing ovarian cancer is 1.6% in the general population. This compares to a 300% increased risk when 1 first-degree family member is affected, rising to 500% when 2 relatives are affected.

Epithelial tumors represent the most common histology (90%) of ovarian tumors. Other histologies include

(1) low malignant or borderline ovarian tumors

(2) sex cord stromal tumors

(3) germ cell tumors

(4) primary peritoneal carcinoma

(5) metastatic tumors of the ovary

Prophylactic bilateral salpingo-oophorectomy is indicated in high-risk women, particularly women with a genetic predisposition for ovarian cancer (ie, BRCA carriers). Surgical prophylaxis decreases the risk by at least 90%. Not all cases of ovarian cancer are prevented as women are still at risk for developing primary peritoneal carcinomas.

The Society for Gynecologic Oncology states that BRCA testing may be indicated when there is at minimum a 5% likelihood of carrying one of these deleterious changes.

If you are Jewish and have ovarian cancer, your likelihood is 28%. If you are jewish and your mother had ovarian cancer, your risk is well over 5%.

That's why Helix Health of Connecticut has teamed up with the Group for Women in New York City. Helix Health of Connecticut sees patients with this world renowned group of Gynecologic Oncologists.

The Sherpa Says: Catching this risk before the disease is ideal. Unfortunately, there are very few tests to identify early stage or predisease. BRCA1/2 are our best shots. Despite an early detection test being in the news over the last few days......I am certain a molecular test will be validated shortly.

Markets being analyzed....

I was recently invited to participate in a survey for concierge practices. Since we run Genomic Medicine/Personalized Medicine practices in New York and Connecticut I agreed. Then the questions came..

Which Services Do you Offer Your Patients?
Choose all that apply:
-Comprehensive annual physical exam

-Referral for assessment at an executive health clinic

-Genetic testing
-Onsite or home blood draw
-Fitness assessment
-Onsite physical therapy or fitness programs
-Nutritional assessment and counseling
-Nutritional supplements
-Onsite body scan or offsite referral
-Biophysical blood test
-Tests from Berkeley Heart Labs
-Acupuncture
-Specialty blood work assessing hormone, receptor, protein, vitamin levels, or other for prevention/wellness purposes

13.
What kind of genetic testing do you utilize in your clinical decision making, if any?

15.
What has been your experience with genetic testing?

Choose all that apply:
NA/Have NOT been involved with genetic testing
I have ordered genetic testing for my patients
I keep up with current literature on genetic testing
I have done past research in genetics
I have participated in Continuing Medical Education (CME) units on genetics
I have taken classes in genetics after residency
Other If other, please specify:

16.
How comfortable are you answering questions from patients about genetic testing?

-I am a genetic specialist or an expert in genetic counseling
-I have some expertise in genetics and genetic testing
-I would work with the patient to research information
-I prefer to work with a genetics expert, then deliver that knowledge to the patient myself
-I would likely refer this patient to a genetic specialist
Other If other, please specify:

17.
Would you support a patient’s interest in obtaining a scan of their genome that would identify their risk of developing certain health conditions?

Yes, I would recommend it
I wouldn’t mind if they did it and brought in the results to discuss
I would not recommend it and would not review the results, but I would be fine with them doing it
No, I would NOT support this

18.
What would be your biggest concerns about genome scanning for health conditions?

Choose all that apply:
NA/No concerns
Not convinced of the value
Not convinced of the reliability
Security of patients’ data
Unnecessary patient anxiety
Uncertain link between results and outcomes
Regardless of finding, my recommendations for a healthy lifestyle will not likely change
I want to wait until more of my peers use these tests
Other If other, please specify:

19.
What potential value do you see in genomics testing for your patients, if any?


20.
What would you want in order to feel more comfortable recommending genomics screening to your patients?

Choose all that apply:
NA/Would NOT recommend for any reason
Clinical evidence
Testimonials or endorsements from medical leaders I respect
Patient testimonials
Journal articles
Co-partnership with leading academic research center
Conference abstracts/presentations
More training for physicians to better understand the risk factors sometimes uncovered in the test
Easy to access support or informational services for patients
Easy to access support or informational services for physicians
Other If other, please specify:

21.
From which medical leaders would you like to see testimonials or endorsements regarding the efficacy of genomics screening?

The Sherpa ;)


26.
What criteria would you use to select patients for whom you would consider recommending genomics testing?

Choose all that apply:
Patients with limited family histories
Patients who would benefit from a focused approach to lifestyle modification
Patients who require additional motivation to adhere to primary prevention strategies such as for cardiovascular or metabolic diseases
Patients in need of a complete wellness and prevention plan
Patients seeking enhanced personalized screening programs such as for cancer or ophthalmic disease
Patients with difficult-to-diagnose diseases like Celiac disease or Crohn’s Age
Level of income
Personality of patient
NA / Would NOT recommend screening
Other If other, please specify:

The Sherpa Says:
This report was designed by an Investment Analyst....my guess....with a price point for testing at 2500 USD....I think we know who this was.....It seems to me that the market is finally being analyzed...... Which is a good thing. My problem is with question 26....Since when does Income Level serve as an indication or serve as criteria to perform a genetic test? ACHHH! The results of this survey would make a great blog post......I asked those guys for the results....maybe they will let me blog about it!

Genomics to Save Your Life and Touch Your Heart

Ladies and Gentlemen. This Video is a must watch for all of my readers. Please watch and pass along. This wonderful artist will present her play in New York City. It will debut this October.





I implore all to watch and pass along. And please, make a donation to support her play. Tickets are available here.

The Sherpa Says:
This is a must attend event....and a must watch video.

Polls closed.....Helicos is right

Over 56% of you believe that full human genomes for 1000 USD will be here within 5 years. Patrice Milos of Helicos BioSciences thinks so too. I am here to tell you that they may already be here.

I had the chance to chat with Dr. Milos the other day. We spent about half an hour scouring the landscape, talking about Helicos' ambitions for clinical utility and their aims in the human research arena. It was pretty salient. Dr. Milos states that in due course it will be a matter of not IF we can sequence a genome for 1000 USD. Instead the question will be whether or not the average consumer chooses to have it done.

In case you don't know, Helicos does tSMS(TM), also known as True Single Molecule Sequencing.....Because of some confidential agreements I cannot tell you exactly what they have accomplished....but it is nothing short of spectacular.

What if you could...
Sequence thousands of samples in a single experiment?
Screen a gene signature against tens of thousands of compounds?
Discover messenger RNAs, micro RNAs and novel transcripts across thousands of tissue samples?
Sequence an entire human genome in a single day... for less than a thousand dollars?
For most of the past decade, that's been the promise of a technique known as single molecule sequencing. It's never been possible....Until Now
To see more click here!


I spent the 30 minutes with Patrice talking about generating databases of genomes for reference. We spoke about the grand dream cohort study of 100k genomes with medical data and care.
With the promise of a billion base pairs per hour.....we could quite be ready for it THIS Year!!!
There are some limitations in read length, etc. That will need to be worked out....and it already is being worked out...But what tSMS(TM) holds for the present and future is pretty impressive.

The Sherpa Says: The Archon X Prize will bring out the best technologies and also bring about the commoditization of Genome Sequencing....and with that bring about the era of truly Genomic Medicine. But in order for that to occur we need clinical researchers to link genome findings to better health records.

What happens when a mandate is exerted????

Here is a quote from one of my readers...

The ACOG mandate for CF testing came out while I was getting my genetic counseling degree. I gave quite a few counseling session to pregnant women regarding CF testing. Unfort6unatley that was in a high-risk OB office where the patients were already undergoing some form of prenatal screening through our office. I know at the hospital medical clinics, no counselor was available to do the CF counseling. It was a big mess.

Then, in 2006 when I was pregnant I actually requested the CF carrier test for myself and my OB did not even talk to me about the test at all. She just wrote a script to get my blood drawn. No family history was taken, no explanation was given about what the test was screening for or what it meant if I was a carrier. I was very disappointed with how it was handled.

A mandate from a medical specialty like the American College of Obstetrics and Gynecology (ACOG) can be very tough on physicians.....Thus they push back and try to prevent mandates. Why is it tough?

1. It increases physician workload to counsel. Something most physicians don't have time to do.
2. The services mandated often cost money......Sometimes that money comes out of MDs capitation (pay) ....
3. It scares physicians, simply because it creates another liability risk for malpractice.

I am certain there are others.....But hopefully you can see why alot of physicians who never learned genetics in medical school or residency are fighting tooth and nail against Genomic Medicine.......

What happens when we introduce MORE mandates, yet don't pay our doctors to carry them out? The shennanigans my readers tell me about, that's what happens!!!! Testing without counseling....YIKES!!! Delivering results via secretaries??? Yahtzee!!!
But remember....the testing is the mandate.......not the counseling.....SAD.

The Sherpa Says: I was just at Coriell the other day talking to their staff about this problem. They were a wonderful crowd....In the end I submitted my sample for their research.....Imagine, the Navigenics service.......for free!!!!!!

California ok with SNP chip testing with MDs

In the New York Times today it appears, California has been satisfied by 2 of the big 3 DTC SNP Chip testing companies. From the article:

Two closely watched companies that offer consumers information about their genes have received licenses that will allow them to continue to do business in California, a state official said Tuesday.

The licenses, granted to Navigenics and 23andMe, should help defuse a controversy that began in June when the California Department of Public Health sent “cease and desist” letters to the two companies and 11 others that offer genetic testing directly to consumers.

I don't think Andrew spoke to the geneticists I work with. I don't think a state license will ever defuse this powder-keg. But I do congratulate both companies on working within the state regulatory system. I appreciate their efforts. It really casts a great light on the non-academic genetics services and testing services.

The companies had argued that they were not offering medical testing but rather personal genetic information services, and that consumers had a right to information from their own DNA. The companies also said they did not need a license because the actual testing of the DNA samples was being done by outside laboratories that did have licenses.

Looks like they needed the licenses after all. This argument was a fallacy. As a practitioner I could say I don't need a license to practice medicine to interpret Liver Function Tests, because I send all of my samples to Quest. Huh??? Exactly.

Ms. Billingsley said the companies also satisfied the requirement for a doctor to be involved. Navigenics already was paying a physician to review customer orders and now it appears that 23andMe might be doing something similar.

This was a needed step. Not only for the State, but also federally as the AMA and ACMG have mandates that will be heavily represented in either possible administration.

New York State also has taken action against at least 31 genetic testing companies, saying they cannot solicit business from New York residents.
Ms. Baker of Navigenics said a resolution with New York did not seem imminent.

I am doubtful New York will even budge on this. They are very stringent with their requirements. Very Stringent.

“We do think in the end this needs to be regulated at the federal level rather than as a patchwork of state regulations,” she said.

What would that regulation look like? We have 2 possibilities.

1. S. 736, the Laboratory Test Improvement Act, sponsored by Edward Kennedy (D-MA), chairman of the Health, Education, Labor & Pensions (HELP) Committee, with ranking Republican Gordon Smith (OR) as co-sponsor, and

2. S. 976, the Genomics & Personalized Medicine Act, sponsored by Barack Obama (D-IL), with co-sponsor Richard Burr (R-NC), both members of the HELP Committee

The breakdown?

While acknowledging that it is important not to stifle innovations or impede patient access, both Kennedy and Obama say federal oversight is needed to assure the analytical and clinical validity of genetic testing and to monitor direct-to-consumer marketing that makes questionable medical claims for unapproved test kits.

Under the Obama bill, S. 976, Congress would solicit outside expert advice before further regulation of genetic testing and genomics. The HHS Secretary is to contract with the Institute of Medicine to study and make recommendations on the key issues. Once the report is submitted, the Secretary is to develop and propose a decision matrix to help labs and other test makers know which types of tests require which level of review and who is responsible for the review––CMS or the FDA, or both. The bill also requests a study by the National Academies of Sciences on incentives to stimulate advances in designing and developing new genetic testing technologies.

The Sherpa Says:

Either way....when you ask for federal regulation.....you should be very careful of what you wish for......

Christina and Jessica beat BRCA1

I certainly hope my friends at Speigel and Grau get in contact with Christina Applegate. As I suspected and mentioned on August 7th......It seemed, based on the limited family history I had, that Christina Applegate was a BRCA carrier. Today, I find out I am correct.

This is timely news as Helix Health of Connecticut is now releasing the CliniCast from May 21st 2008: "How Genomic Medicine is Changing the Management of Breast and Ovarian Cancer". Interestingly, this was the day which GINA was signed into law. In fact it happened right when Jessica Queller announced to the world that doctors who are "too old" to learn genetics should retire.

Well Jessica, I am here to teach those doctors.....If they don't want to learn, then I agree. They should retire.

If you want to learn more or even take a listen to our CliniCast, you can pre-order them here.

In addition, if you are listening Christina, you can get a copy today. Just email me at thegenesherpa@gmail.com

Ms. Applegate is scheduled to appear on a one-hour TV special, "Stand Up to Cancer," to be aired on ABC, CBS and NBC on September 5 to raise funds for cancer research. I am looking into how I can help with this fantastic fundraiser.

The Sherpa Says: BRCA is scary, breast cancer is even scarier. When you know your risk, you can detect disease early and even prevent it in the first place. That is the definition of Personalized Medicine.

4 Million for Education

Today I am shooting from the hip. Normally you guys can figure that one out from my posts, but today it is coming fast and furious.

Issue Number One:
"Will predisposition testing result in adverse selection for long term care insurance?"
So what happens when that Navigenics test (sorry, they don't test, the do the medical interpretation) says you are at risk for Alzheimers? Take a look at this report???? It looks as if the magic 8 ball says....."It is likely"

How do we solve this problem? How about long term care insurance mandates like the health care mandate in Mass? Try again.....How about genetic testing as a requirement to get insurance? GINA doesn't prevent that.........Unfortunately. I have a serious idea.....The big risk that these people think may happen usually manifests in the face of family history....Why don't insurers just do a better job of taking family histories? For my big life insurance policy, they just asked about my mom and dad(Who I haven't seen since I was 13).....what kind of risk stratification is that??? More importantly, why shouldn't insurers be able to risk stratify?

Issue Number Two:
Why aren't we starting to see the public asking for pharmacogenetic tests? You would figure, this would be the biggest demand from our overmedicated society? If you are taking drugs, do they work for you? Do they make you ill? It looks like labs will be offering these tests....But are they selling them? Are physicians ordering them???? No.....Why? Education and Fear. Adult learners require not only education, but also need emotional buy in and clinical application......These are the keys. Even the guys at Frost & Sullivan have shown this.

This is the huge market. The problem......for each fantastic report, there are bad reviews....The problem, meta-analyses are suspect and can be spun.....but often do not perfectly analyze the data. But, most docs don't pay attention to that.....What they do pay attention to is a lawsuit. So why have we not started to see these suits????? There has certainly been a lot o talk about these...

Issue Number Three:
Why are businesses and VC funding suspect genetic testing when they could be promoting the health of the public by supporting clinically actionable testing and services??? Well, at least most VC, Angels and Businesses have been showing a track record of bogus testing support. I think this is because there is a lack of genetics education for these business people. If they employed solid clinicians who have experience in this field, we could see some really amazing things come to fruition. I have a feeling this will start to shape up shortly......

The Gene Sherpa Says:
Think on these things. I have been thinking about these things for quite some time. Send me some of your thoughts....and as always......email me to start a discussion.

The New BRCA....this time its the Colon!!!

This is a fantastic review. I have been very careful trying to avoid hyping tests. I do this because we need validation and some evidence for use would be nice. The problem is that sometimes a test is so powerful that it should not be sat on.

This was the case with the BRCA genes. Even in 1996 Francis Collins was warning about testing without really thinking out the consequences. From his 1996 article in the New England Journal of Medicine.

The benefits of presymptomatic testing to determine susceptibility to common cancers such as those of the breast, ovary, colon, and prostate are potentially substantial. Nonetheless, it is critical that we create safeguards to ensure that the benefits of testing exceed the risks. The technical ability to perform tests for mutations should not be confused with a mandate to offer them. In the long run, the identification of BRCA1 and other cancer-susceptibility genes should permit the development of new and more effective therapies, so that physicians can not only predict future risks, but also reduce those risks reliably and safely before disease occurs.

I say this because we now have evidence of what I would term a genetic risk factor akin to BRCA1.

Recently published and talked about on Think Gene.....

Germline Allele-specific Expression of TGFBR1 Confers an Increased Risk of Colorectal Cancer.

Why do I say this is the next BRCA and may be even bigger?

New cases of colorectal cancer in the US in 2007: 148, 810
Deaths: 49, 960

How does this line up with Breast Cancer? New cases 182,000. Deaths 41,000

Pretty similar. What percentage of Breast Cancer is "hereditary" approximately 7-10 percent.

BRCA, we think accounts for a significant amount of this.

Colon Cancer? Way more....maybe up to 40% are familial.....but due to a specific gene? Far less 5%...until now.

You see, having a family member with colorectal cancer puts your risk up 400% from the general population. Even having polyps in the family increases your risk.

With that in mind, this study:

Germline Allele-specific Expression of TGFBR1 Confers an Increased Risk of Colorectal Cancer.

Was just published in Science. What is bad about print journals???? This was submitted in April....they (the researchers) have been sitting on this.....and likely creating a clinical test.

What did they find?

Conservative estimates suggest that ASE confers a substantially increased risk of CRC (odds ratio 8.7; 95% confidence interval: 2.6 to 29.1), but these estimates require confirmation and likely will show ethnic differences.

This was a surprise for some, but we had seen hints of this in JAMA. It turns out they estimate 20% maybe up to 30% of familial colorectal cancers have issues with reduced expression of the TGFB receptor subtype 1. This is due to a specific mutations which can be tested for in research and may soon be clinically available at Helix Health of Connecticut and other genetic providers. 30% of 30% of 148,000 per year!!!!! That is 15,000 people who will potentially positive.......that's just the afflicted members not even their family members in the US! This is a much larger number than breast cancer.

I was speaking with a Venture Capital firm this week when a really smart VC partner asked me......how can you project testing to reach this level in 3 years when the current data show a much smaller number? I answered him with this. We are finding new genetic risks that affect a much larger population. This is disruptive technology that could reach not only the small amount of rare diseases that exist today. We are talking testing that would benefit the over 300 million persons in the US. Now that is rapid growth! Tests like this are those harbingers..

So with that being said, some caveats:

1. This is only in caucasians....replication is needed for other ethnicities
2. Clinical testing is not YET available

3. No screening protocols have been clinically defined yet. BRCA took 10 years to have most of the kinks worked out. I am certain the public won't tolerate that long for this test. But it may need a few years of study....

The Sherpa Says:

An odds ratio of 8.7 for developing colorectal cancer in carriers of these alleles is a huge risk akin to the BRCAs. Even more impressive is that this could affect WAY more patients than the BRCAs. So I say, let's start studying this clinically and launch the test as soon as we have a good screening strategy!!!

By Secretary or By Professional Report

A recent study caught my eye. Done by multiple centers.....

from the Division of Laboratory Systems,* Centers for Disease Control and Prevention, Atlanta, Georgia; the Wadsworth Center, New York State Department of Health, Albany, New York; the Albert Einstein College of Medicine, New York, New York; ARUP Laboratories and the University of Utah, Salt Lake City, Utah; the Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington; San Ramon Valley Primary Care, San Ramon, California; the Genetic Services Laboratory,** Sequenom Incorporated, San Diego, California; and the Department of Human Genetics, Mount Sinai School of Medicine, New York, New York.

What did they investigate? Simple....how genetic tests were orderded and how results were given. What really got my goat was the results.

First as a preface....the AMA in June put out a statement against DTC genetic testing Resolution 502, A-04. D-480.987 in case you want to check it out. This statement says:

Our AMA: (1) recommends that states restrict the performance of clinical and laboratory genetic testing to individuals under the personal supervision of a qualified health care professional......

Also in the AMA policy manual is E-2.131.....

Physicians who order genetic tests should have adequate knowledge to interpret information for patients. In the absence of adequate expertise in pre-test and post-test counseling, a physician should refer the patient to an appropriate specialist....

So with that backdrop I give you the study "Ordering Molecular Genetic Tests and Reporting Results. Practices in Laboratory and Clinical Settings."

To understand better the contributing factors to such compromised care, we investigated both pre- and postanalytical processes using cystic fibrosis mutation analysis as our model.

Ok this will be great! CF testing. When was the last time the OB went over pre and post test counselling for carrier status???? I can't wait to see the results...

1. We found that although the majority of test requisition forms requested patient/family information that was necessary for the proper interpretation of test results, in many cases, these data were not provided by the individuals filling out the forms.

2. We found instances in which result reports for diagnostic testing described individuals as carriers where only a single mutation was found with no comment pertaining to a diagnosis of cystic fibrosis.

3. Remarkably, a pilot survey of obstetrician-gynecologists revealed that office staff, including secretaries, often helped order genetic tests and reported test results to patients, raising questions about what efforts are undertaken to ensure personnel competency.

If you have any question as to why OB/Gyns get sued more often than anyone else.....look no further than the results of this study!

The Sherpa Says: The real pickle is this. The American College of Obstetrics and Gynecology recommends that every pregnant woman get "screened" for cystic fibrosis mutations. So the OBs are forced to do this testing.....oh wait, no they aren't. They could actually refer patients. Or even better, they could hire a geneticist. But why do that when they could just have their secretary do that work? Scary stuff!!! This makes DTC look pretty warm and fuzzy.

Feeling Better!

Thank you to all the well wishers out there. Your encouragement has gotten me through a pretty tough time. But I am up and running again. I hope you spread the word to other listeners.....The Sherpa is Back......

So with that, I have about 10 minutes to post prior to our clinic conference here at Yale. We had lots of great cases today. But most notably, I have begun to realize how important it is that every patient with the diagnosis of autism be seen by a geneticist. What does that mean? It means our specialty is going to be even more strained. How can we combat this?

1. Train more geneticists
2. Train other healthcare providers to do genetics
3. Have the counselors do 2-4 more years of training to become licensed healthcare providers
4. Have the consumer go directly to the internet, order their autism panel, get a written report online, and have a nice day!!!

That's my point with all of this. If 4 were an option, why would we ever have medical professionals?????

So the rate limiting step here is education and training......How do we do that?
I will share something amazing with my readers shortly....once I finish my U34 grants.....

The Sherpa Says:
Did anyone watch the opening ceremonies of the Olympics? The drummers had drum sticks that glowed.....if you looked at them closely, they looked like chromosomes....Or maybe I was just hallucinating from the fever?????

Another star with cancer.

I am crawling out of bed to comment on another person who has breast cancer. Christina Applegate diagnosed at 34 years of age with Breast Cancer. She apparently had received an MRI which caught this cancer early.

Why was she getting breast MRIs?

Her mother, Nancy Priddy had breast cancer at 37 years of age. To me that speaks of a hereditary syndrome. Not knowing the rest of her family history, it would make a lot of sense if she was getting MRIs and is a BRCA carrier. Why MRIs? Some insurers pay for these in the case of BRCA carriers.

This is a good catch. Lucky for her.

The Sherpa Says: I wonder if Jessica Queller has reached out to her?

Please Don't deactivate me!

I have been so very ill. I will return to posting when I have the energy. Sorry to all my readers.

-Sick Sherpa!

Muscle Pain from Statins? Time for a genetic evalutaion!

In a wonderful demonstration of how successful genetic research on pharmacogenomics needs to be done. The SEARCH Collaborative Group successfully demonstrated the power of GWAS nested in other studies. This will be the hallmark of all great medication studies for the next 50 years. Do I mean GWAS? No!

I mean genetic analysis of the outliers in response to the medication being studied. I only ask myself, why in the hell hasn't pharma been doing this for the last 10 years????? I have my suspicions, but I'll never mention them in public.

So why am I so excited? Well......you know how the DTC companies test you for SNPs that give you odds ratios of 1.3 or less??? Imagine an Odds Ratio of 16 for developing statin induced myopathy!!! I was just talking to the founder of one of those sequencing companies worth billions of dollars about this the other day!!! Odds ratio of 16.9

Uhhhhh...Yeahhhh....that is a pretty good chance of getting the myopathies associated with this super common medication. How is that for immediately clinically relevant. Have the polymorphism?.....Don't take statins...instead take Fenofibrates.

This study was signed sealed and delivered to the door of the makers of Zocor(Merck). I sure hope they license that test!!!! Oh wait...this will likely be sold by deCode. Caraiso just told me that this SNP is on all of the big 3's chips! So who will contact their patients...sorry/customers? If the MD ordered the test....it would be the MD's duty........This is why the government is trying to regulate this testing.....for this type of follow up. This is a great study it needs follow up!

How was it done? From NEJM...

Methods: We carried out a genomewide association study using approximately 300,000 markers (and additional fine-mapping) in 85 subjects with definite or incipient myopathy and 90 controls, all of whom were taking 80 mg of simvastatin daily as part of a trial involving 12,000 participants. Replication was tested in a trial of 40 mg of simvastatin daily involving 20,000 participants.

At first, I balked.....80 mg of Zocor. That's a whopping dose! Who the hell uses that much Zocor? So I tried to dismiss this study....but it was the replication in the 40mg Group that got me.....

So what did they find?

The noncoding rs4363657 SNP was in nearly complete linkage disequilibrium with the nonsynonymous rs4149056 SNP (r2=0.97), which has been linked to statin metabolism. The prevalence of the rs4149056 C allele in the population was 15%. The odds ratio for myopathy was 4.5 (95% confidence interval [CI], 2.6 to 7.7) per copy of the C allele, and 16.9 (95% CI, 4.7 to 61.1) in CC as compared with TT homozygotes. More than 60% of these myopathy cases could be attributed to the C variant. The association of rs4149056 with myopathy was replicated in the trial of 40 mg of simvastatin daily, which also showed an association between rs4149056 and the cholesterol-lowering effects of simvastatin. No SNPs in any other region were clearly associated with myopathy.

Why am I salivating over these results????

1. 16.9 is a huge Odds Ratio in a region where we know there has been lots of literature reporting the issues with Organic Anion Transporters and the bad effects of statins.

2. The replication in a clinically useful cohort.....40 mg of Zocor....there are tons of people on that dose.

3. Statin Myopathy can cause kidney failure from rhabdomyolysis(muscle breakdown). It is a dangerous side effect! Another clinically useful point!

4. There were NO OTHER SNPs associated with anything!!! The odds of that are preposterous! That IMHO means this is a very valid SNP. With everything, I suggest replication and then the marketing of this test to the physician. With the OTC Zocor in the UK....maybe they have an interest in DTC????? Or maybe not

The Sherpa Says:

Pharma are you listening? This is the way to save your medications and save you from lawsuits. The way to stay alive is by developing diagnostics that protect your patients and doctors.....If you don't follow this model, you will perish. When this study is replicated and the test available through a CLIA certified lab, Helix Health of Connecticut will test their patients for this very important genetic polymorphism.....As for the big 3 screens changing medications......Dr Agus should stick to Heme-Onc. The SNPs associated with heart attack in the SNP scan are separate from cholesterol....and statins have not been proven to lower risk via any mechanism other than lipid lowering....Either way, he would be better served testing the organic anion transporter.