Family History Tidbits

In my search for useful news today, I have come across something near and dear to my heart. Karen Lu at M.D. Anderson has posted on the importance of taking a family history. Her spin is obviously tilted towards cancer, but the benefits of family history or just as important in diseases like heart disease.

From the site:

“Family gatherings are the perfect time to ask family members detailed questions about their health history,” says Karen Lu, M.D., co-medical director of the Clinical Cancer Genetics program at M. D. Anderson.
“It is important to gather information about the health history of your parents, siblings, grandparents, aunts and uncles, and even your cousins.”

She points out that there are some red flags to watch out for in your family.

1. Early onset of Cancer. (I say not only cancer, any disease is important here)
2. Family member with 2 or more "related cancers" (These include things like breast and ovaries. For more info see here)
3. Two or more family members who have related types of cancers. (Too bad some insurers require 3 members to be afflicted in order to pay for BRCA testing)

If you find some of these red flags you should at a minimum ask your physician about genetic evaluation. If you live in the CT, NY, NJ area give Helix Health of Connecticut a call. Genetic Testing may be appropriate for you and evaluation is needed.

Genetic testing involves looking for abnormal genetic changes in a person’s blood sample. People who inherit abnormal genes from a parent may be at increased risk of developing cancer.

“The benefit for the cancer patient who tests positive for an abnormal gene is that doctors can use this information to determine if they are at increased risk for a second cancer and to help family members,” says Molly Daniels, a genetic counselor at M. D. Anderson.

For family members, the benefit to learning that a close relative carries an abnormal gene is that they too can be tested to determine if they are at increased risk for developing cancer.

Those who test positive may begin routine cancer screening exams at a younger age than what is usually advised for the public. High-risk screening enables health professionals to detect cancers as early as possible when there is the best chance of successful treatment and cure. Those who test negative can be reassured that they are not at increased risk because of family history.

The Sherpa Says: The major risk factor in both heart disease and cancer is family history. Perhaps more so in heart disease. Evaluation for these risks need to be done on an ongoing basis. Remember, your family history changes with time. So if you have taken your family's history, up date it yearly or when something you know has changed. A great tool for this is found at the HHS website!

TCF7L2 Strikes again, This time it's the Finns

The Latest edition of Mendel's Garden is up at Scienceroll. If you haven't seen it, the Gregorian Rap All-Stars video is a must see!

It's official. I can say without any doubt that the gene TCF7L2 is somehow implicated in diabetes. Another whole genome association study was performed and results were published in the American Journal of Human Genetics.

The study which performed because there only exist a handful of genes that have been implicated in the genetics of diabetes. These include PPAR gamma, TCF7L2, KCNJ11, CPN10, FTO. And because GWAS is hot now. They selected 4 populations, all Caucasian. 200 Finns with diabetes and 200 without, similar numbers of Ashkenazi Jews, 100 soccer hooligans from Manchester and 99 affected Brits, as well as 100 Germans with diabetes and another 100 without.

What they found was not surprising. TCF7L2 SNPs rs7903146, rs7901695 and rs122255372 were all replicated as linked again with ORs of 1.6-1.7. They also found several candidate loci. None which were that impressive when attempted to be replicated.

So, what does this all mean? Well it means that there is an increased risk for diabetes if you have any of the aforementioned changes in your TCF7L2 gene. But how does that help us? Now that it is shown to be linked, we need some data on how to prevent diabetes in the carriers of altered TCF7L2.

Does anyone have good data on this?

The Sherpa Says: Sometimes I do eat humble pie. That being said, I will not recommend TCF7L2 testing for anyone. Importantly because there are several SNPs associated, not just the SNP that deCode tests for. There is more to this diabetes story than meets the eye.

Why Can't We Be Friends?

A recent study in the New England Journal of medicine implicated a gene called FTO (Fatso) in increased risk of obesity. If you had one copy, then you had a 33% increased risk of being obese. 2 copies? 67% increased risk. On average people with FTO weighed 7 pounds more.

It is true that we know of some increased risk due to genetics. However, a study published this week in the NEJM suggests perhaps your friends may play a larger role than your genes.

In this study, if you listed someone as your friend, and your friend became obese during the time they were studied, then your risk of becoming obese would be 171%. Much greater than the risk of carrying 2 copies of FTO.

What about the 6 degrees of separation effect? Wht if it was a friend of a friend? Well they found that the increased risk was less than that of FTO's effect. However, there still was increased risk.

The Sherpa Says: This study was performed on the famed Framingham Heart Study offspring. They attempted to control environment by evaluating neighbors. It does turn out that there is no relation between neighbors and obesity.....Unless they are friends...This tells us that social networking is an indicator of risk of disease. Intuitively this makes sense. Smokers hang together, as do illicit drug users, and perhaps as this study shows over-eaters. Why can't we be friends? Because you are fat.

Diabetes Risk Model Without Help from deCODE!

A study was brought to my attention by Helix Health of Connecticut's Genomic Counselor Sarah Coombes. This study which was published in the journal Archives of Internal Medicine(a very respected academic journal for primary care physicians) showed that Parental diabetes, obesity, and a low good cholesterol were better predictors of diabetes risk than complicated algorithms and complex clinical models.

The incidence of type 2 diabetes is skyrocketing and predicting onset can help us guide interventions. In the public health schema it can have tremendous effects when anticipation guides development of preventative strategies. This is the case with heart disease and cholesterol lowering modifications.

Parental history of diabetes, obesity, HDL(good cholesterol) less than 40 predict diabetes onset at a greater rate than ANY GENETIC TEST OUT THERE!

Most importantly, your insurance pays for the HDL and glucose tests.

The Sherpa Says: This study which evaluates the offspring of the famed "Framingham Study" is excellent. The point with personalized medicine is not just sending genetic tests. True, this study needs to be validated in all ethnicities not just those who were found in a suburb of Boston (Caucasians). But, I would use this risk stratification tool on all of my Caucasian patients. True personalization comes not only from genetic tests, but also from other traditional labs AND family history!

Dr Collins reports from the Front Lines

In the second of my 3 maybe 4 part post I will detail Dr Collins' report from the Front Lines of the Revolution!


First some notable quotes

• "2007 is going to be a landmark year in Genomics and Medicine"


• "We all have ticking timebombs in our genome, you could guess most of them from family history.........But not all of them"


• "We shall have the major genetic risk factors for common diseases in 2-3 years or less"

Without further ado I will break his talk down into sections. Dr Collins', feel free to correct anything in this.

"Notes From the Front Lines"

1. DNA sequencing is undergoing a revolution. I almost felt that he had been reading The Sherpa prior to giving this lecture. I had commented on 454 recently. On powerpoint he showed the technology behind 454 and Illumina. he did not comment on nanopore, but I think that's because it is not ready for prime time. In addition he did not comment on RainDance..............I feel he knows something big is going to happen in sequencing real soon.


2. Common Disease gene discovery is skyrocketing. In this subset Dr Collins draws our attention to several great discoveries. He talked about GWAS (genome wide association studies). He even mentioned the numbers and power required to get a decent study. I am always amazed by how the public and physicians think this type of stuff is easy! He made mention of the macular degeneration studies which implicate 2 gene polymorphisms in over 50% of the disease!!! He spoke about Diabetes, something that he has been studying for 14 years. He did not metion DNADirect and DeCode's TCF7L2 testing via DTC........ I think this is a hot topic. Especially because Sharon Terry was at the conference. A great woman who is now advising DNADirect. She is a patient advocate in the truest sense. Without her GINA would not be around.


3. Diagnostic capability is advancing. In this subgroup Dr Collins mentions Abacvir toxicity and pharmacogenomics testing. He also give us some insight into the pharmacogenomics process and how we can use these tests. By this time my teams' heads are spinning. I am reminded of my prior post. Coumadin was mentioned by Dr Collins too, the 1 hour test was not. Trust me, this flank is moving full speed ahead!


4. ELSI needs to be addressed “Will we increasingly think of ourselves as hapless victims of our genotype?.......Attention to ethical, legal and social issues is more important than ever,” Dr Collins aptly points out the fact that we have some serious loopholes in our legal protection. In addition, we have to think about ALL of the uses and misuses of this information. Later on I'll tell how Representative Kennedy is super focused on this topic.

The Sherpa Says: Ok, this is too much info. Let's digest this and move on later today..... Oh and Francis is the Man!!!

Hemochromatosis stories.

Lisa Lee posted about "House" last night. It made me laugh. I couldn't help but think how the media really portrays health care. It is down right scary. Most, like the media over-hype the non-dramatic and fail to catch the essence of medical culture. It is also scary how they miss the REAL issues. Did you know that in real life if you are "coded" you have less than a 15% chance of leaving the hospital? On TV it is over 75% And the way they portray disease......don't get me started :(

But what's even scarier is having to suffer through disease. I always like to check out the support blogs and this is one I feel strongly about. They express their difficulty with phlebotomy, the traditional treatment for Hemochromatosis.

Which brings me to my last comment. The American Gastroenterological Association recommends Iron Studies to evaluate for Hemochromatosis, not genetic studies. There are some shortcomings to this approach.....What if you are a pre-menopausal woman? Sure your iron will be lower than most with Hemochromatosis. But it will be elevated. The moral of the story, know your ethnicity, know the symptoms, and stay aware.

Lastly thank you to all that have visited The Sherpa's Shoppe. I am not looking to make any money, I just wanted a shirt that said "The Gene Sherpa" and didn't feel like buying 20.

DNA mutation....Not so fast my friend.

Today results were released from a Genome Wide Association Study. This revolutionary type of research does promise to bring us closer to true personalized medicine. That being said........
The study published in Science today by DeCode and several academic institutions (U Penn, Duke, Emory) shows that a loci on Chromosome 9 (long arm) 21 has been linked to an increased risk of heart attack. This study was almost simultaneously replicated by Dr McPherson in Canada at the Ottawa Heart Institute. The study links are not up yet. I will post the abstracts when they are. This is exciting news, however.

1. This is just in a block of genome, not a gene per se
2. The risk with this polymorphism is 1.6-2 fold
3. In Scheuner's analysis of family history, the risk with one afflicted sibling is approximately 2.8 fold
4. As my good friend Dr Lei at Eye on DNA suggests, this will not change the way we practice medicine....yet. First we need to start teaching doctors how to take a family history, then we can move to QTLs and genotyping.

I hate to be the lead balloon but,

The Gene Sherpa Says: While interesting and it should help discover further causes of heart attack this DNA "test" is not even close to ready for prime time!

Hsien-Hsien Lei

Just a brief post today to tell you that there is an excellent blog being started by Hsien Lei PhD. She has been at the helm of a highly successful genetics blog called Genetics and Health. She is now posting on her new blog Eye on DNA
I am looking forward to this new start. We all wish her the best.
On a not so light note, I have been embroiled in a hot debate with Lisa Lee from a direct to consumer company. She has been extolling the benefits of predisposition testing for TCF7L2. When I posted this she had no response:
From Genetics and Health

"Last one I promise.The TCF7L2 is involved in signalling and may very well represent what we
call a developmental predisposition. The family of proteins it plays a role in is Wnt signalling. This is involved in the development of the gut. It is fishy to raise the possibility without mentioning that the damage could have already been done in utero. Similar predisposition may be involved with COPD (emphysema).

From NEJM Volume 355:306-308 July 20, 2006 Number 3“Does this new genetic information have any practical health implications? At first glance, TCF7L2 is not the most attractive of drug targets, since it is closely involved in fundamental developmental processes. The main effect of the high-risk single-nucleotide polymorphisms in relation to diabetes may be developmental and may not be amenable to therapeutic manipulation in the adult patient.”

Do you see how confusing the data is? I sure do.The jury’s still out.
At least in my mind.
-Steve

More Than DeCODE found!!

In one of the most comprehensive evaluations of diabetes risk genes "researchers from the University of Michigan, the National Human Genome Research Institute, the University of Southern California, the University of North Carolina, and Finland's National Health Institute, have identified at least four new genetic variants associated with increased risk of diabetes and confirmed existence of another six.

The findings will be posted today in the online edition of the journal Science" This news was in Medical News Today. The findings include several genes which were not found by the DeCODE company. The Science papers confirmed six other genetic regions that others had previously identified as having a connection to type 2 diabetes.
Kári Stefánsson, the chief executive officer of deCODE, notes that a smaller sample size may help explain why his team didn't report two of the three new variants found by the three groups that pooled their data.
The story is not over for diabetes. I will maintain that any genetic testing being offered to the public right now is premature. We have replication studies. But what is really needed is analysis of a risk panel.

Dave Altshuler quoted in Science Now and the Gene Sherpa agree :"The findings are just the beginning of what GWA studies will accomplish, notes David Altshuler, the director of the program in medical and population genetics at the Broad Institute in Cambridge, Massachusetts, who helped lead one of the teams reporting results today. The next step is to sequence these regions and confirm the relevant genes. Figuring out how they work "is going to take great creativity and insight," says Altshuler, as will determining how and when to apply the results to patients." So would I run out to take the Direct to Consumer TCF7L2 test?...NO. It likely will just confuse the situation.

Personalized Medicine is coming

I am back! What a fun week in San Diego. I was at a conference for Program Directors (Responsible for training resident physicians) in Internal Medicine. During my absence a few things have come up. But first I want to talk about the conference and how almost all program directors acknowledged that they do not teach genetics in their curriculum. Moreover, several expressed interest in our curriculum. I am so excited that these teachers are now realizing the power of genomic medicine.
That being said.....Appropriate use of the genome brings great results. Misuse and blatant promotion such as that done by a direct to consumer testing center in San Francisco (I will not say their name) will only lead to sullying of the geneticists' reputations.
On Genetics and Health there is a post which lead me to a website that was promoting risk factor testing for diabetes. Like any other path I will lead you through, there is good, bad, and unknown. First the good.
Diabetes is an awful disease and the longer it is untreated the worse the outcomes. So naturally I am excited about being able to diagnose it quicker. BUT this test does not diagnose, it only shows increased risk.
Here comes the bad.
In fact, the risk of carrying this gene polymorphism is not even half as much as having a sibling with Type 2 diabetes. Why would a company promote this test rather than promote taking a family history? The answer is simple, because they make MONEY off the test or interpretation and not off taking a family history and counseling in person. I have no respect for that. In fact, people will be amazed to know that this company makes all of its profit from marking up test costs or non face to face services, and serving as an "educational" resource. What education leaves out that the best screening test for hemochromatosis is iron studies? Shame on them.
Lastly, the unknown.
Now that I know this risk, how do I use it clinically. There is no study showing that metformin or a PPAR gamma here will prevent the onset of diabetes in this risk group. What I am saying is....before we go down this road 3 things need to be done

1. A 3 generation family history
2. Research on prevention in this high risk group
3. Companies looking to make a quick buck off of you on testing without clinical utility need to be punished. Or at least I can lead you away from that confusing and dangerous path.

If you do wish to do in home testing without the help of a TRAINED genetic specialist who examines you and takes a full family history, then you risk the difficulty of test interpretation, appropriate follow up, and possibly improper care as a result. I hope you choose wisely.