Friday, March 28, 2008

Oh When the Saints

That's right, I am off for the big N.O. this next week. I will be attending the Association for Program Directors in Internal Medicine annual chiefs' meeting. I am on the faculty and will be giving a session guessed it. Genetics curricula in Internal Medicine. I will be accompanied by Mike Murray MD of Harvard, Mark Babyatsky MD of Mount Sinai, Cyrus Kapadia MD of Yale and Charles Seelig also of Yale New Haven Health/Greenwich Hospital.

We will be getting the group motivated about teaching this important topic. I have to tell you that this is the rate limiting step. I think that the AMA can hand out as many brochures as you want...but change starts from within.

So...The Sherpa will be taking a Vay Cay for about a week. I won't stop monitoring the BlogoNome but my output will be diminished....unless there is some really juicy stuff.......

The Sherpa Says:
Keep Climbing............

Thursday, March 27, 2008

I lost my Train....

So last week I asked the question. "Where would we be if we had a 1000 USD genome by next year?"....But more importantly I asked "Who would lose if we had a 1000 USD genome by next year?"

So who would lose?

I am having a hard time coming up with these. I think they tend to breakdown into several groups

1) The group who benefits from not being able to target medicines and diagnoses.

2) The group who would is scared to know what the secret of the genome holds

3) The group not nimble enough to change their practices and adopt new technologies

4) The group whose genomes hold some horrible secrets and disadvantages that have previously gone undetected

5) Those who I have left out, the unknown unknowns

So let's address one at a time

First up.....Who benefits from trial and error medicine? Who benefits from not having cheap genome sequencing

1 Big the drug.....doesn't another and another and another

2 Hospitals.....Chest Pain?????.......Admit to rule out heart attack........Chest Pain Again????.....Admit and repeat the process again..... To a certain extent this is true.

3 Device Makers........Obesity????.....Have a LapBand..........Funny Heart Beat?????.....Have a pacemaker. We are talking thousands of dollars per device people!!!

4. Knome....(Sorry George)

5 Patented genetic tests.....
6 Not the SNP people....their products now are merely the entry level players....They will switch to whole genomes ASAP....Trust me.

Can you think of others? I bet you can.....So who are they?

The Sherpa Says:

This is how we need to think about the barriers and how to break them down. We need to show who loses how they can win. Then we get them invested in the process. That is what the Wall Street Journal Article is all about.

Tuesday, March 25, 2008

500 Hospitals want to know....

Lots of stuff happening online today. I just left a conference call where I was the invited guest panelist along with Robert Resta CGC. The Advisory Board Company and The Innovations Center presented an Issue Brief entitled-The Genetic Testing Frontier: Impact on Clinical Care, Market Opportunities. Hundreds of hospitals were online wondering how they too can get a piece of the action.....

Also....did anyone read the Washington Post today? Genetic Testing Gets Personal again another article on this "revolution" non subscription link here

"We call it consumer-enabled research," said Linda Avey, co-founder of 23andMe, based in Mountain View, Calif. "It's about changing the paradigm of how research is done."

Well Said.......You could also call it uninformed cohort analysis...."Free Kits?" Come-On....nothing is free. Davos, you sold your DNA for some fancy flash animation and trinkets....I am guessing the Belmont Report is not required reading in MBA schools...Hey guys don't worry, here are the Cliff Notes
The Belmont Report explains the unifying ethical principles that form the basis for the National Commission’s topic-specific reports and the regulations that incorporate its recommendations.

The three fundamental ethical principles for using any human subjects for research are:

(1) respect for persons: protecting the autonomy of all people and treating them with courtesy and respect and allowing for informed consent;

(2) beneficence: maximizing benefits for the research project while minimizing risks to the research subjects; and

(3) justice: ensuring reasonable, non-exploitative, and well-considered procedures are administered fairly (the fair distribution of costs and benefits.)

These principles remain the basis for the HHS human subject protection regulations.

Paradigm of how research is done???? Isn't that why we developed IRBs? To protect from those who want to change the paradigm and injure the patients? IMHO these companies need to immediately develop research protocols and IRBs. End of story....nothing less. The consumer should be allowed to at least ask questions to another person.

It can be entertaining, Venter said, to learn one has a gene for soggy earwax. "But if you're on the receiving end of one of these tests and are told your probability of having a serious problem is 62 percent, what the hell does that mean?"

And that is assuming the results are correct. As it turns out, many gene tests today search for DNA patterns that have been linked to a disease or trait in only one or two studies. Such findings are often overturned by later research.

Enter the trained professional.....This is precisely why we need more Sherpas!!!

Dr Venter is completely correct....the brick and mortar where professionals exist is the transition point. Even 500 hospitals online today acknowledged that. Now where do we get these individuals?

Exacerbating the problem is that virtually no one is watching over the industry. The Food and Drug Administration does not regulate most gene-based tests, and there is no federal proficiency-testing system for companies offering them.

Enter the SACGHS and EGAPP...2 organizations devoted to helping best practices....In addition, the ICOB at the Delaware Valley Personalize Medicine Project will also help shape this future.

"It creates an air of charlatanism that doesn't help the field," Venter said.
All told, concluded a study in this month's issue of the American Journal of Human Genetics, "There is insufficient scientific evidence to conclude that genomic profiles are useful in measuring genetic risk for common diseases or in developing personalized diet and lifestyle recommendations for disease prevention."

That is my number one concern. Here's why...geneticists and genetic counselors require referrals from physicians who don't speak genetics, but watch the national news and read the New York Times...If they link Medical Geneticists with Scientific Match.....There Ain't no way in hell any self-respecting, butt-covering, good physician will refer patients to such "Qwacks" simply due because of the confusion. All press is good press? Don't think so...especially when the NEJM posts such a confusing article failing to clarify the difference.

"I very much worry that all this emphasis on a 'gene for this' and 'gene for that' raises the risk that people will conclude that that's the whole story," Collins said. Instead of empowering people to make healthful changes in their lives, that could simply make them "more fatalistic," he said, "in which case, what's the point?"

Me too Francis...Me Too....

The Sherpa Says:

To climb the mountain we need unreasonable people that won't quit....Corporate and Academic can exist together...provided they do the right thing. Do it yourself surgery is probably just as "Revolutionary" so why isn't anyone on that money train? BTW the pic is of do it yourself LASIK.....I bet that is a best seller.

Saturday, March 22, 2008

Match Day for Doctors.....Hooray!!! NOT!

Imagine training extremely hard for 4 years....AFTER college...only to find that you will have to train for another 3 or for before you ever will be able to say you are a board certified doctor....Now imagine that you may not get your first or second or even third choice as to where you will train for your last 3 to 4.

Every year medical students in their last year go from state to state interviewng for positions to train in the specialty of their choice. This trek last approximately 4 months from November to March. In Late February the medical students and the residency directors make their "wish list" much like an NFL Draft list...looking for their next All Star Doctor. This process culminates in Match Day...a day when all the US medical students open up an envelope and find out where they will spend 80 hours a week for the next 3-4 years.

Unfortunately, you can't be ranked if you never go for an interview..... So why in the Heck am I talking about this on a personalized medicine blog? Because this day determines how many residents match in the field of Medical Genetics.....

Despite what many DTC genetic companies may say, the true lasting power of genomic medicine lies with the physicians. So naturally the future lies with our future physicians....

For many years the most physicians enter the field of Internal Medicine, this year is no different 4800 total medical students will be training in Internal Medicine. Half of those will be US grads. Why does the percentage of US trained students entering US residencies matter? Because it shows how popular a field is for the US students......assuming the US grads get their picks first.

So what were the stats? Click here to see So where is the future?

The highest percentage US grad filled field? 100% in Fields like Dermatology-low work, load high pay

The lowest percentage? Medical Genetics 25%

Next we look at how many spots were filled as a determinant of popularity

The highest percentage filled? Once again Dermatology, etc 100%

The Lowest? You guessed it Medical Genetics at 50% filled. 10 spots!!! 5 filled!!!

This is consistent with the current training environment where only 50% of all training positions in medical genetics are filled. In dermatology you can make 1 million USD a year...In medical genetics 100-160k USD....

The Sherpa Says:

Match day? Maybe if Medical Geneticists made the money that ScientificMatch makes.......
How can we fix this gap? Corporate Genomics claims to have an answer.....I think mine is better.

Thursday, March 20, 2008

They're HEEEERE!!! Navigenics in New York

Well in a move to trump NY or a business plan that does include physicians. Navigenics will Launch April 8th in NYC!!!

That's right

From a counselor's email sent by

Dear xxx,

Navigenics invites you to be one of the first people in NYC to experience first-hand a leading-edge approach to health and wellness.

Navigenics is launching its first genetics service April 8th. We truly believe this company will revolutionize the way we think about our health. Our first service, called the Navigenics Health Compass, tests for genetic risk markers for 18 actionable common conditions—cardiac disease, several cancers, Alzheimer’s among them—and arms you with specific information on how you can mitigate your individual risk for developing each condition, including personal genetic counseling sessions and customized health and wellness content. To celebrate the launch of our first service, we are coming to New York City for two weeks in April (April 8 – 17) to host a series of exciting and informative events. We will be installed at a SOHO location, and I encourage you to join us for some of our events. (Please see the calendar invitation below.)

Please help us celebrate this transformation for medicine: from a “sick care” model of “wait and see” to the emergence of early risk detection. The time has come to empower individuals with the opportunity and knowledge to take preventative steps, and a hands-on approach to their family’s health and wellness!

All the best,
The Navigenics Team

Now it will be interesting to see how their competitors 23andMe and deCodeMe react. Our practices stand ready to pick up the pieces and serve as an information source for both patients and physicians who have lost their compass, or just want to learn about this new technology.

The Sherpa Says:
I'll be there. How about you? To all my physician freinds, give me a call and I can explain what the hell is going on.... You should go to these events....Seriously, they look pretty impressive

Wednesday, March 19, 2008

366 Days Later

Readers, Colleagues, Friends...
Well, That day is upon us. It is 1 year ago that I started this journey.

Here is the post that fateful March Day


So I have no idea where to begin. Which is why I will just start with the Stats.......

Only 17% of patients with familial colon cancer risk were referred to appropriate genetic counseling according to a study at Harvard.
Prenatal counseling is not offered 9 of 10 women who meet indications!

Only 37% of MDs know that BRCA genes can be passed by the father!

We have a lot to cover and I look forward to sharing my solution to this huge problem. How in the world can we expect to implement Personalized Medicine in all its glory without having some Genome Savvy physicians? Oh....Those geneticists? Too bad almost 90 percent are pediatricians and have no clue what ischemic heart failure is.

So..... 3 lawsuits, 2 threatened libel cases, Tens of thousands of viewers, a brush with fame, an almost TV spot, an appointment to advise a personalized medicine project, meeting some of the greatest people, launching my solution to the problem, the rise of corporate genomics, the launch of an Amazing Network of Genetics Bloggers, watching DNA Direct arm up to fight 23 and Me, Seeing Navigenics delay to prepare for the Google Wars, Multiple VC consultations and the best damn year ever, despite Boston Winning......I say "The journey is never finished. At Year One I can truly say we have just begun to ascend the mountain" even JAMA thinks so...

First I would like to thank my family for putting up with the incessant blogging, during dinner, during breakfast, when something strikes me.....

Next to thank the community which gave me the opportunity to grow. Berci, Hsien, Walter, Ric, Misha....I could go on and on....please know that you all hold a very special place in my heart. No matter what views you hold, you were always there for me.

To my readers "What a year!" The Sherpa would have been worthless without your opinions, your eyes, your information. Thank you for all the inside scoop you have provided. I hope our relationship will bring even greater synergies! We can get up this mountain....together....all of us.

The Sherpa Says:

Now we must climb....To Quote My good friend Master Yoda

"Do or Do Not, There is No Try."

Tuesday, March 18, 2008

What would we have?

I implore you to think about it. Investigate it. What would we have if we could identify billions of base pairs? Could we give it to you in a neat 23andMe package? Could we hand you the printout Gattaca style? What would we have?

Today I received an email from a very nice gentleman from Suracell. He had sent me an interesting report. In this report I felt that I had said similar things about nutrigenomic testing. I asked "What do we have?" This report only strengthens my beliefs. To look at what we would have, we need to look at what we NOW have. GWAS through SNPs, SpitKits..because these studies are called genome wide.....some are inferring that to mean genome scans....Which they are not....even if they were....which they are not....what can we do with these things?

The knee jerk is "Nothing" The real answer is "It depends"

It depends on whether or not we have adequate data defining actionable items. But why does this even matter when the global market for personal gene testing is valued at approximately 730 million USD and growing....who in their right mind would want some of that? Why not make the quick buck for now and stay around for the real party later??? It very well may destroy us, that's why. Enough about now what about the 1000 USD genome? Well what if "it depends" suddenly became it depends a whole lot less of the time? That is precisely what we would have if whole genome analysis was available for 1000 USD.

We would have a whole lot of data that we may or may not be able to analyze. Then, if we can analyze the data...How will we act on it? I am simply amazed by the power of the genome...I have seen it damn men to heart attacks and strokes, I have seen it punish those who do not pay attention to it. I have also seen it bless individuals making them impervious to the effects of hard drinking and cigarettes. I have seen it help cure cancers and I have seen it stupefy physicians. What I haven't seen it do is explain to us how we can use it. We still have to figure that out Ladies and Gents....

So what if we have a 1000 USD genome? What would we have?

The Sherpa Says:

We would have a whole lot of work to do.........Stick around, we are only at the base of the mountain. THAT is the answer to where we would be. Now I want to know "Who loses?"

Sunday, March 16, 2008

First Take by Mailund

The first blog response comes From Dr Mailund of Denmark. Thomas is an Associate Professor at the Bioinformatics Research Center (BiRC), University of Aarhus, Denmark.

His response is telling and it essentially says what is true....we would initially be "Lost" but not for too long

My goal is to figure out ways to analyse full sequence data for disease mapping. With full sequences, a few things change compared to SNP chip data.

First, of course, there is the matter of scale. Now you get 6 billion nucleotides per individual instead of 2×500K or 2×1M as with SNP chips. (This is a huge Point!!! This doesn't include methylation and other epigenetic phenomena either)

Second, you are no longer looking for indirect signals, so there are no tagging and multi-marker methods will not be needed to boost the power of indirect signals. You have all the variation observed (but the types of variation is much more complicated).

Third (and perhaps most interesting), the kind of signals we are looking for will change. With SNP chips and tagging SNPs, we are looking for high-frequent variants with modest effect. High frequent variants is all we are tagging (and these have a modest effect if we are still looking for it, if they didn’t we would have found them ages ago). With full sequencing, we will be able to look for low frequency variants as well.

The Sherpa Says:
We would still need more research.......But I am certain it would come in a hurry! Who's next with their take?

Saturday, March 15, 2008

A thought....

What if we had a 1000 USD genome by next year? Where would we be? What would we have? What problems would that create? Who would benefit? Who would lose?

I have been thinking alot about this lately. Mainly because I had known for a while that the Applied Biosystems' Product was coming in under 60k. Trust me....under 60k USD. My friend and ex-President of TV Guide had sent me something this week and I wondered how quick this would move up the charts and into the press.

So I ask my readers..."Where would we be in 1 year from this date if we had the capability to sequence a whole genome for 1000 USD? No not the SNP scans being paraded on the Today show...A whole genome, CNVs and all. What problems would that create? Who would lose? Who would benefit?

I have some ideas and will post them in the coming weeks....Starting with "Where would we be?"

The Sherpa Says:

Let me know what you think....
I am so getting sued by ABC!!! Or NBC take your pick!

Wednesday, March 12, 2008

Maybe not 99% similar. Suracell? Not so Sure

Today I want to post on several things that you may have been reading about. The first of these is the twin studies on copy number variation and methylation. Huh? I said "copy Number Variation and Methylation" What are these? I thought everything was about SNPs? I am certain you must be asking yourself these questions. Well, fear not. Unfortunately methylation and copy number variation do not have millions of dollars, corporate giants, VC or PR firms pushing their importance....

But these unique changes make us probably on the lines on 90% similarity. Which, when you look at each other makes a little bit more sense. Right? Just like the fact that 18k genes encode our complex organism. How in the heck does that happen? Well I am here to tell you that SNPs are just the first chapters of our genome novel. Which is a great thing...Imagine if we said...."That's it, end of the story...we know it all" I think that day would be a very sad day for all of us....because on that day G_d would certainly play a joke on all of us. This reminds me when my friend said "You know, I've got it all figured out." The next day, he wrecked his car and then found out he was going to be a daddy.....Well, I guess everything that was in his previous reality was figured out...

So what is the deal with the twin studies? Identical twins are supposed to be identical right? Incorrect. Huh? Well these things have been shown in other studies as well. Let's face it, as geneticists we know that even identical twins are not so identical. In the 1980s and 1990s there were multiple reports of things like Non-random X inactivation leading to X-linked diseases in females. Yet we were still teaching mendelian genetics in university and not teaching any genetics in medical schools.

We don't have it all figured out...and the stuff we have figured out is probably not ALL figured out. A recent article in the American Journal of Human Genetics reminds us that we need to take everything in perspective and always double check things....especially when it comes to your health. They review the science behind Suracell and Salugen and Sciona.....But they do it with a sneaky name A Critical Appraisal of the Scientific Basis of Commercial Genomic Profiles Used to Assess Health Risks and Personalize Health Interventions

That certainly sounds like they reviewed 23andMe and deCodeMe doesn't it? Well....they did not. However they do comment that the SNPs used in the "Nutrigenomic" companies...which were already given the "Honorable Mention" by the GAO. What is the take home on Nutrigenomics?....Find the right company and understand that our understanding as physicians and scientists is pretty young....We have only gotten through the first chapters...

The Sherpa Says: Let's keep reading this book of life....Act when we can but not in an irrational manner. Let's rely on the science....and let the Sherpas guide us...not the press or a rock solid public relations firm. Last but not least, we may be able to sequence a genome for 60k....but we still have a HUGE knowledge and Manpower Gap!

Monday, March 10, 2008

60 is the trigger for Alzheimers

Finally, a weekday post! I know, I have gotten in this vicious cycle of posting on the weekends and keeping them up for the first few days of the week, just so those readers who don't check the rss or even switch on a CPU on the weekends don't miss a beat. Listen, I read Tim Ferriss' book too...but I now have to step it up.....

Today I want to bring an interesting topic to light. Why are people scared of genetic testing? Is it the discrimination (which doesn't exist) or is it something more deeply rooted like "Genetic Determinism"? In counseling for things like breast cancer risk, some often say..."You may have outlived your risk for early onset breast cancer" This is a sticking point for me.....Who ever outlives genetic risk? Completely, I mean. There are so many variables out there that can give you cancer...who is to say that just because you are 65 your BRCA mutation won't give you that cancer? I couldn't be hard pressed to say that so vociferously. I say this because even with the strongest genetic influences there is always an exception. This is exactly the case with Alzheimers and ApoE4.

Well now a study recently released called the Arizona ApoE4 Cohort Longitudinal Study of Cognitively Normal Individuals (Say that 3 times fast) indicates that 60 may be the age of kickoff for cognitive decline in ApoE4 carriers.

According to the article in Internal Medicine News......
There is a particular pattern of decline in ApoE4 homozygotes (2 copies) that tend to precede any diagnosis of mild cognitive impairment (a stage prior to full blown alzheimers or other dementia). Or prior to anything that can be seen on radiologic brain imaging....

So what does this mean for the clinician? It is huge....Instead of outliving your risk...we now may identify those with ApoE4 who will likely get Alzheimers......CAUTION, these results are currently being replicated and I wouldn't want to promise anyone that we have a perfect ApoE4 phenotype detector quite yet. But it is important to have this....Why? Because up to 10-40% of homozygotes will NEVER develop Alzheimers. So when can we say you have "Outlived your risk"? The answer is never...but we can say "You will be less likely to have ApoE4 related Alzheimers than someone who is your same age with this cognitive deficit." That is what should be said.

Now the real quandary..."How can we stop it from getting worse doc?" That is for another post.

The Sherpa Says:
Too many in the genetics field are quick to give medical advice. I warn that perhaps we should check our training and liability insurance before we start doing this. I recommend that all of us in this field work together to provide the best care possible. I never say never and never say genetics as in life, there are NEVER any definitive answers...except "sometimes" and "it depends" That being said..........We should always be performing routine screening exams on carriers of any genetic changes. Confused yet? Don't be. Just follow my lead.

Saturday, March 8, 2008

Coriell Honors the Sherpa

I have to start posting more on weekdays....but when the press is slow and the studies aren't good...I have a hard time giving you fluff. Don't get me wrong. Some sites do a nice job of recapping things posted by other sites and monitoring the crowd for you. I think Hsien, Walter, and Berci do a tremendous job of this. In addition my favorite writer Misha also has a funny thing or two to say at Genomeboy. I also love to point you in the direction of our DNA Network which always has some interesting news.

I am writing today to talk about a pretty interesting project going on at Coriell. I had posted on this prior, but now it is personal. I have been invited to sit on The Informed Cohort Oversight Board (ICOB) for the Delaware Valley Personalized Medicine Project. This is a tremendous honor and I want to thank Dr Mike Christman CEO/President of Coriell for inviting me. Personally, I think that this seat is right in my wheelhouse. Especially since I have been monitoring these SNP studies for several years now. The ICOB which will meet for the first time in June and determine which variants are medically actionable is set to lead the way for similar projects. We plan to debate and write opinions on these items.

For those who don't know about this project let me give you some more information. Unlike the exome project of Dr George Church, Coriell is using the standard Affy 1 million SNPChip. But like Dr Church's project we will be meeting to debate the significance of each polymorphism and most importantly, define medically actionable SNPs. There are over 250 participants now and unlike Dr Church's project, We are not funded by Google. But the project does need some solid, responsible funding....I know they will find that.

Do I dislike Google? No. I think they have a great model. Should they enter healthcare? Only if they vow to take the Hippocratic Oath, Form an IRB and submit to the same stringent standards as any Academic Institution. Otherwise.....No Way! I have always loved this doomsday scenario, check it out! This coming from a guy who is an Avid fan of Jericho. Has anyone else had issues with blogger lately????? Coincidence? Hmmm.....

The Sherpa Says:
I am honored to be participating in this wonderful project. Please take a look and see that it has all the hallmarks of an upright and worthy cause. I hope all future investigators can follow this path.....

Thursday, March 6, 2008

Warfarin in the NEJM and the Westchester WAG

In a brief clash of civilizations today, I happened to be reading the Westchester WAG in the physicians' lounge. What is the Westchester WAG? It is a swanky monthly publication put out to showcase the high and mighty in Westchester County, NY. Yes it is one of the most affluent counties in the country, yes so is Fairfield County CT oh wait....isn't that where you have offices Dr Sherpa? Yes.....I have one on Park Avenue as well so it should come as no surprise that I was reading the WAG....Well maybe it should since I am from a small town in Pennsylvania and from a humble middle class family.

While flipping through the swanky weddings I stumbled across an article written by Isadore Rosenfeld a physician reporter who also practices cardiology in New York City at Cornell. It's funny that he wrote about coumadin and risk for bleeding, simply because he was standing next to me in the Emergency Department a few months ago taking care of a patient of his. This patient had a significant bleed in his brain because his blood was too thin on coumadin.

But what stunned me was five seconds after I dropped the WAG I looked at NEJM Online. Guess what? The group from Vanderbilt released some of their data on the study of CYP 2C9 polymorphisms and VKORC1 polymorphisms. Truly amazing. Even more amazing is that when you ask an internist about this you may get "I think I read about that in the WAG"....

Why in the hell do upper class socialites get this information before Internists? I am so fired up about this that I am speechless (Almost). Even crazier is why most internists/cardiologists have no clue about these studies. I think that we must solve this problem before we get anywhere in genomic medicine/personalized medicine. How can we do this?As I sit on a conference call planning our presentation at the Association of Program Directors in Internal Medicine spring meeting and we all are asking the same question. I am working my tail of on these solutions.

What was neat in this clash of social groups is that I began to realize that the NYT is right. Especially after Amy Harmon published her article about the Russian who had 350k to burn. Next time you are looking for material Amy......give me a call! The rich will absolutely want this information and use it for better health (if they see us), the poor deserve these services but likely will not get them. As for my parents the middle class, good luck finding an internist who knows that CYP450 is more than one enzyme.

The Sherpa Says:

This NEJM data suggests that VKORC1 may be more strongly linked to INR variability than CYP 2C9. Something that was not so clear. Does this mean we only have to test for one of these genes? I doubt it. In fact this makes even more the case for testing both genes. Why? Because there a less people with SNPs in VKORC1 than in CYP2C9. And Lastly, what in the hell is wrong with medicine? How did we forget that science matters? We didn't, we just never thought that genetics mattered. Now it is too late for these physicians to learn a language....Maybe we need rosetta stone's help?

Monday, March 3, 2008

New England Journal, Prostate Cancer and Babel

Remember when I said that all of these association studies had weak Odds Ratios? I also said in the Sherpa's golden rules of genome wide association study that any OR less than 2 is probably not better than a family history. Here we have a study in the NEJM listing a powerful combination of SNP data AND Family History. This was e-published back in January, but I draw your attention to it again as it deserves notice.

In a significant meta analysis it is shown that the OR if you have a first degree relative with prostate cancer is 2.5 I hope Genome-Boy and his trusty side kick Prosty are reading!

Well, this study and its shortcomings...There are some. This study Blows mere family history out of the water. This study, dubbed CAPS, evaluated Prostate Cancer in Sweden.

The analysis of SNPs revealed 5 SNPs which had significant risk implicated...Here's the kicker, if a person has 4 SNPs and Family History, then your Odds Ratio for Having Prostate Cancer is.....get this 9.46 compared to the men who had none of these factors.

Take That PSA and Digital Rectal Exam!

Now where does this study have shortcomings?

1. It is retrospective and this is subject to bias, therefore needing prospective analysis before we will use it.

2. This population is a relatively homogeneous population that breeds nationally

3. Only one of the SNPs has an identifiable gene. Without a gene, we can only guess what role the SNP may play let alone devise a medication or treatment to offset these effects

The Sherpa Says:
This is what I am talking about! When replicated prospectively...and this will be, this will be a powerful tool to use for risk stratification. To my journalistic friends, please don't report the Odds Ratio as if it were a relative risk! To my prostate prone friends....cheer up. Prostate Cancer is rarely a killer.

Saturday, March 1, 2008

CF "success" story

Today I am writing about something I call truly Personalized Medicine. This topic hits near and dear to my heart and I am going to talk about this because it is an ethical dilemma.

The recommendations for genetic screening by the American College of Medical Genetics, the American College of Obstetricians and Gynecologists, and the National Institutes of Health were issued in 2001. According to recent letter in the NEJM it turns out that the birth rate of children with Cystic Fibrosis has dropped.

The number of infants born with cystic fibrosis in Massachusetts decreased by 50% from one four-year period to the next according to this letter in the NEJM. They attribute this to the Newborn screening available in Massachusetts since 1999. In addition they also report a drop in those patients born with "supposedly" the worst outcomes...those with two Delta F508 mutations. This is the most common mutation and has been "associated" with worse outcomes. But not all rests on this gene, there are modifiers of this disease.

Here is the most important point they make.....The children born with CF in the future may actually have less significant disease and may need to have less aggressive or less early interventions.

But here's what they don't say.....Preconception screening for this disease is important, but a highly personal choice..... despite what the ACMG and ACOG say. There are some children who are doing just fine with CF. As for adults with CF like the 74 year old patient who I diagnosed a few years ago, I am certain they would not want to have never been born. Especially my friend who now has CF AND 2 very healthy children. He would want us to be able to predict worse outcomes preconceptionally. We are on that road now. But until then we still will be doing Preconception evaluations as well as Prenatal evaluations. This is because the aforementioned patients are the exception and not the rule.....

Genetic Issues are complicated. Despite this seemingly great report, there is more to this story....Much More. This is why I have had issue with haphazardly Shipping off CF testing for prenatal care and the poor guidance give by some OB's/Midwives regarding test results. This is not to say all OB's do a poor job of giving pre and post test counseling....but the data indicate that quite a few do. Only 19% self-reported thoroughly reading ACOG's Guidelines on CF testing!!!! Only 1 in 5 OB/Gyns can answer 5 fairly simple questions regarding CF least in some groups of this study. This indicates a knowledge gap. I have seen it personally and it is quite distressing.

The Sherpa Says:
To get the best evaluations, you need people trained in the field, skilled with this complicated type of testing AND its complications. This is why I ask that every Ob sending genetic testing at least calls a geneticist or genetic counselor. We cannot assume that everyone knows what we know! If you are a pregnant or planning please ask your OB to let you speak with a geneticist if she sends genetic tests.....