One of the more promising areas of personalized medicine may be the utility of pharmacogenomics in treatment or prevention of disease.   One of the successful examples of a pharmacogenomic application in medicine has been the use of Herceptin on HER2+ expressing breast tumor cells.   To illustrate how personalized medicine can impact the success of medical treatment a recent editorial in Forbes was published by a biotech representative, Adriana Jenkins, whose last wish was to ask Congress and pharmaceutical companies to support more personalized medicine strategies in the future because the development of Herceptin extended her life by 9 years.   Other examples of pharmacogenetics which have the potential to impact medical practice include warafarin dosing with genetic variants in  VKORC1 and CYP2C9 genes and clopidogrel metabolism with variants in CYP2C19 that produced an FDA to create a warning label.   But research into these associations and their clinical utility are just beginning.   Pharmacogenomics could play a significant role in tailoring medicines to particular individuals in both increasing efficacy and reducing or preventing adverse drug reactions.

Does smokeless tobacco use have the potential to reduce the harm from smoking and improve public health overall?   Since congressional approval for the FDA to regulate tobacco products in June, this question has come to the forefront of public health policy and now two papers are published on the topic, an in-depth epidemiologic review in Regulatory Toxicology and Pharmacology (authored by me) and a paper that outlines the debate in BMC Medicine by David Timberlake.   The reduction in health risks from smoking needs to be balanced against any potential adoption by non-smokers who may develop a tobacco habit if smokeless tobacco use were to be promoted as a safer alternative to smoking tobacco.  While the health effects of smokeless tobacco appear greatly reduced compared to those associated with cigarette smoking, there is little research examining if smokers would actually use smokeless tobacco as a substitute for cigarettes or tool to quit smoking. Well-designed clinical trials need to be conducted to determine if smokeless tobacco use would be effective tool in getting smokers to quit smoking and would be socially acceptable to the majority of smokers.

Swedish snus

Also, this research has primarily focused on moist snuff use (like Swedish snus) which is tobacco in a tea-bag like pouch which is placed in the oral cavity.  The health risks of other forms of smokeless tobacco, in particular, locally made products in Asian and African countries, may be greatly different.  Some of these products have additives which are known carcinogens.   More research is needed and likely more questions will develop before we will know if promoting smokeless tobacco use for smoking cessation would help improve public health overall but it is an important area to investigate with FDA regulation of tobacco on the horizon.

I finally got to watch Nova’s documentary on ‘The Ghost in Your Genes’ last night and was very excited to learn about the progress that epigenetics research has made in the last few years.   As a believer that most complex diseases arise from gene-environment interactions, epigenetics has fit perfectly into a model for explaining disease risk.   The work on how one identical twin can develop later in life, while the other does not,  is such a prime example of  how the environment can make alterations to a person’s genome over time.  Researchers have underestimated (and some still do) the effect of methylation of DNA and other alternative genetic  mechanisms affecting DNA expression on the risk of complex disease.   This is likely why geneticists have not found strong support for genetic  variants (i.e. SNPs) in their genome-wide association studies.   From the perspective of a genetic epidemiologist, I have long thought that in order to determine susceptibility genes for complex disease, researchers need to look at environment effects (i.e. epigenetic influences) in the genome simultaneously.

NIH is starting to recognize the importance of understanding the epigenome and its role in human disease and recently announced the funding of several grants on this topic.   Much more complex modeling and research studies are going to have been undertaken in order to start piecing this puzzle together but it is a very exciting time to see how it will unfold.

Happy Gene Hunting!

I find this article particularly interesting because my master’s thesis examined a large dataset (SEER registry cases) of prostate cancer cases and controls for factors which interacted with an increased 3-fold risk of having a first degree relative with prostate cancer.   While the results of this study did not find an association between an increased number of sexual partners and prostate cancer directly, it did find a highly significant association and interaction between a high number of lifetime sexual partners (20+) and men who had one first degree relative with prostate cancer (RR: 4.5, 95%C.I.2.4-8.5). Unfortunately, due to political reasons (a senior person at NCI wanted to publish his own analysis on family history risk), I was not permitted to publish this finding.  I have always suspected that having a large number of sexual partners in a lifetime would be associated with increased risk of sexually transmitted organisms, which could easily be a virus similar to HPV.   Since many of these viruses ubiquitously infect the majority of people are exposed to them, the rate limiting factor for how soon a man develops prostate cancer (and it is thought that most all men will develop this cancer if they live long enough) may depend on his personal genetic makeup and resistance to viral infection and/or viral mutation of somatic cells in the prostate.

So what do you think?  Would love to hear any opinions on this!

http://www.the-scientist.com/blog/display/55886/

Yesterday, President Obama  officially signed into law the congressional bill to allow the FDA to regulate tobacco products.  After many years of proposing such regulations, I am still in state of awe at how rapidly Congress passed such a bill in both House and Senate and got legislation on the president’s desk within months (lightening speed for passing anything in the government).  The big white elephant in the passage of this bill will be exactly what kind of effect it will have on public health and the tobacco industry.  While the bill does not have the authority to ban cigarettes, the legislation of product development and marketing will likely have a significant affect on the sale of tobacco products. Financing the FDA regulation of tobacco will likely increase the cost of cigarettes and tobacco products, which may decrease their use, and/or may tilt the scale in the opposite direction and possibly create a black market for unregulated tobacco products.   It is still too early to tell how this historic legislation will pan out, but it will sure be a fascinating development to follow in upcoming months.

After the conference, some of the speakers were taken on two-day excursion to Kos, which was the birthplace of Hippocrates. The intensive care doctors participated in a re-enactment of the Hippocratic oath under Hippocrates plane tree. Then our group also visited the archaeological site of Asclepieion which was one of the first hospitals, church and medical school and where Hippocrates developed the practice of medicine. What an experience!

This particular group of doctors had been discussing critical care practice on their internet digest for years and finally got to meet each other in person. The meeting host, Dr. Antonios Liolios, became our Kos tour guide and took us to Diamond beach (with gorgeous Mediterranean waters), numerous Greek tavernas where we ate lots of fish, saw sunsets and had a day-long boat cruise exploring more Greek islands.

The typically serious and workaholic nature of these doctors was beaten into submission by the second day of the trip whereby they were forced to relax under the warm sun and in the Aegean sea and eat and drink as the Greeks do!  As with many conferences, such experiences facilitate great conversations (science and otherwise) and allow for the development of strong connections and potential collaborations between scientists.  A video clip of some of the adventures of our tour can be seen here.  (website link TBA)