Now that accessing your genetic information is cheaper than buying a Google Smartphone, now what? What can you get from it? How can you use it? Just as important, but less asked - how do you protect it?

The journal "Nature" joins the debate with a full online issue devoted to the personal genome revolution and its implications. For a fee or for free, you can squeeze more information out of the SNP data or full sequence you got from the commercial genome services you paid for initially. For example, you can get an idea of your risk for a certain disease. With so much information at your fingertips, is everything believable? Should you change your lifestyle because you have one variant for some disease risk? How many "risky" variants does one need anyway? Should you stop running because a variant reveals an increased risk for exercise induced ischemia? Should your doctor change medications because of information on one SNP? One of the Nature articles tackles the issue of how genetic-susceptibility information affects medical practices and lifestyle choices.

However, what personal genome, and the genome-wide association scans in particular, failed to accomplish is to discover the heritability of certain disease risks. Despite the promise and hype, GWAS only revealed small effects of common alleles and nothing that explains estimates of heritability. Are those estimates wrong, or are we looking at the wrong places?

Nature also takes on the issue of mandating consent. On one side there is informed consent and protecting the privacy of the individual, and on the opposing end is global justice and the advancement of "global, collaborative biomedical research". Can we have protect the individual without impeding science, or is there no other way but to choose one or the other?

The Nature editorial began with "research is needed into the way individuals use their genomic information, and into protection from its abuse by others."

Well, then, we certainly have our work cut out for us.

Image credit: Newscom

(Image credit www.about.com) 

A University of Carolina study monitoring 1200 newborns from the ‘Isle of Wight cohort’ found that first borns were more likely to carry a gene variant which raised their risk of developing an allergy before the age of 10.  The study suggested that a first born experienced different conditions in the uterus from subsequent siblings.

The researchers measured levels of an antibody called Immunoglobulin E (IgE) in the babies’ umbilical cord blood.  This is known to play a key role in the development of allergic responses.   First born babies were more likely to have high levels of IgE, and those that did were also more likely to show signs of an allergic response when they were subsequently tested, using a skin prick test, at the age of four and ten.

The researchers also believe they may have pinned down the genetics behind the difference to variations in a gene called IL13, which controls production of a stress hormone called a cytokine, which in turn influences levels of IgE. They found that first born children were more likely to carry a variant of IL13 which raises levels of the cytokine, and in turn IgE.

The researchers believe that birth order may affect expression of the gene during the foetal differentiation and development.

Lead researcher Dr Wilfried Karmaus said:

“We were not surprised that birth order had an effect on the development of the immune system, but were surprised that this interaction persisted at least through age ten … Our findings add to the evidence that allergic reactions are programmed during pregnancy and then effect the disease in later life. … This finding may partially account for the increasing prevalence of asthma and allergies in children in the last 30 years, primarily seen in the western world, as developed nations’ birthrates continue to decline.”

He said that if a way to modify those conditions could be found to make them more like those experienced by later born children, then potentially it might be possible to prevent 20-30% of all cases of asthma and allergy.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2366045

Elaine Warburton  www.geneticsandhealth.com

  MRI of a migraine

Migraine is the most common cause of episodic headache, and by far the most common neurological cause of a doctor’s visit. It affects some 15% of the world’s population.

Researchers from Helsinki University, Finland and the Sanger Institute, UK were able for the first time to convincingly demonstrate a genomic locus to be linked to migraine susceptibility in two diverse populations - 1700 patients from 210 Finnish and Australian families. This is especially interesting as Finnish and Australian populations are genetically distant.  It also tied together previous research, resulting in very robust evidence for pinpointing the susceptibility region.

Researchers identified one gene locus on chromosome 10q23, which showed significant evidence of genetic linkage in both populations studied as well as in the replication study. The gene locus was especially strongly linked to female migraine sufferers.

According to the researchers, this study gives new hope to deciphering the migraine pathways and therefore discovering targets for future treatments, as well as discovering the first migraine gene variants.

Elaine Warburton  www.geneticsandhealth.com

G&H’s INTERVIEW WITH NAVIGENICS

Navigenics approached Genetics and Health for an interview. With so much written about similar genomics companies such as 23andme, Knome, deCODE genetics, I was intrigued to learn more about this company.  In particular, Navigenics appears to be the only company within this industry genre who provides a comprehensive wellness model – a healthcare model that Opaldia, the genetic screening and health surveillance company I founded, endorsed whole-heartedly. 

I interviewed Navigenics’ Medical Director Dr Michael A Nierenberg MD, clinical professor of medicine, emeritus at Stanford University to find out what makes Navigenics stand out amongst its competition.  He was most candid in his responses and the company has been open and transparent in responding to my follow-up queries, for which I am most grateful. 

The following article takes an in-depth look into Navigenics’ genomic services including how the company has positioned its services in relation to its ‘competition’ but importantly how Navigenics answers some of the ethical issues surrounding the whole field of genomic testing. The article has been divided into the following sections:

Navigenics #1 - ”My genes, my health, my life – who are Navigenics?”

Navigenics #2 - ”A stroll through your genomic park – about the test”

Navigenics #3 - ”SNP testing – can it be used for disease risk assessment?”

Navigenics #4 - ”Low penetrance v high pentrance genes”

Navigenics #5 - ”Corporate or pragmatic genomics”

Navigenics #6 - ”Privacy, insurance, GINA and ethics”

Navigenics #7 - ”The barriers to success!”

Navigenics #1 -  ”My genes, my health, my life – who are Navigenics? 

The much anticipated launch! 

April 8^th, 2008 Navigenics Inc launches its genomics service In New York. 

It has branded its service as “Navigenics Health Compass”.  

In its launch literature the company writes: “Navigenics aims to transform medicine from a ‘sick care’ model of ‘wait and see’ to the emergence of early risk detection.  It aims to empower individuals with opportunity and knowledge and to take preventative steps and a hands on approach to their family’s health and wellness” 

Navigenics – a veritable who’s who in genetics and business 

Navigenics has some highly influential supporters including Kleiner, Perkins, Caulfield and Byers (KP) and Sequoia Capital who have recently invested just under US$4m.   Amongst its heavy hitting Board members, co-founders and partners are David Brailer, until recently the Bush Administration’s point man on electronic health records and more recently Chairman of Health Evolution Partners, a private equity fund that invests in healthcare.   

Company co-founders are Dietrich Stephan, a Director at the Translational Genomics Research Institute and David Agus, a protein biomarker researcher at Cedars-Sinai Medical Hospital in LA.  Navigenics CEO Mari Baker was KPs ‘executive in residence’ and is former President of BabyCenter a website for parents. 

Also advising is politically connected Greg Simon, now President of Michael Milken’s FasterCures organization and previously Al Gore’s chief domestic policy advisor. 

Navigenics has close ties to Affymetrix and uses Affy’s gene chip (23andme uses Illumina’s chip).  Affy’s former associate general counsel Stephen Moore is now Navigenic’s general counsel and the company’s VP Business development, Sean George was also at Affy.  Amy duRoss, Navigenics Head of Policy and Business Affairs, was formerly with the Californian Institute of Regenerative Medicine and is also Navigenics’ spokeswoman.

Navigenics #2 - A stroll through your genomic park – about the test

The Navigenics service 

When you sign up to the Navigenics service you effectively enrol as a member and not as a patient or customer.   For US$2,500 you subscribe to an annual package which includes a genomic scan to identify your lifetime risk (compared to an average American male or female) of developing 18 core, treatable diseases such as heart disease, Alzheimer’s and type II diabetes.  Included in the package is on-line and telephone support from experienced genetic counselors who will hand-hold you throughout the process and be available to discuss your results in ‘easy to understand’ language.   

Over time, Navigenics will be adding additional information and tests to its core service portfolio.  As a subscriber to the service, you will have access and be advised of any updates and how they relate specifically to your health risk profile.  Ongoing annual subscription for the Navigenics service will be at a nominal annual subscription, currently US$250 pa. After subscribing you will receive a saliva collection kit.  Once you have provided a saliva sample you will be asked to send the kit back to Navigenics’ CLIA certified lab in California, where your DNA will be extracted and scanned. 

About a month later, you will be informed of your test results via your own personal account within a secure area of Navigenics’s website.  The results also come with an explanation of what they mean and the impact they may have on your overall health risk profile.  In addition there will be guidance and recommendations on how to mitigate against any identified health risk through your personalized health action plan. 

For example, if you are a female, your profile may contain the following results: 

Alzheimer’s              Yourself  8%            Average population   17%

Breast cancer          Yourself 14%           Average population   13% 

This is interpreted as you are at lower risk of developing Alzheimer’s during your life compared to the average female but at higher risk of developing breast cancer during your life than an average female.  Regular screening for breast abnormalities may well be a sound investment for your ongoing wellness.   Dr Nierenberg comments “Navigenics wishes to foster an ongoing partnership and relationship between members and the medical communities.  This is achieved through an educational program and repeated contact. The genetic screen only provides part of the health picture so our members need to be counseled on the fact that as there is also a large environmental component involved in disease development, so they may never get it.” Genetic counseling and having adequate access to this service is of paramount importance to Navigenics.  Elissa Levin, heads up the company’s genetic counseling services.  Dr Nierenberg describes the counseling team. “The counseling team provides members with clinically based knowledge to promote a greater understanding of their health risks, to decrease anxiety at every step of the way and to encourage them to take positive steps to live as long and healthy a life as possible.” 

Navigenics #3 - SNP testing – can it be used for disease risk assessment?

Navigenics has focused on around 100 of the most definitive research papers on SNPs (single nucleotide polymorphisms) that have been most strongly associated with 18 particular diseases such as breast cancer, type II diabetes, cardiovascular disease.  The company has built an algorithm (mathematical computer program) that estimates the risk of a healthy person developing a disease if their genome has the relevant SNP. 

The company has spent immense time and financial resources on engaging its panel of scientific and clinical experts to analyze the many hundreds of SNP association studies.  Says Dr Nierenberg:  

“It is a pre-requisite for Navigenics that any SNP to be included within its core panel must have undergone rigorous scientific and clinical evaluation and had the supporting research replicated in an appropriately peer reviewed paper. Functional data and magnitude of effect are also taken into account, but studies are not automatically excluded if functional data is unavailable or the effect estimate is small.  That being said, there is currently nothing on our panel with a relative risk less than 1.1 of developing a disease if the associated SNP is carried.”

99% of human DNA sequences are the same across the entire human population.  However, variations in DNA sequence can have a major impact on how humans respond to disease, the environment and drugs & medicines. SNPs are DNA sequences that occur when a single nucleotide (A,T,C or G) in the genome sequence is altered.  For example - AAGCT to ATGCT.  For a variation to be considered a SNP, it must occur in more than 1% of the population.  Many SNPs have no effect on cell function, but many could predispose people to disease or influence their response to a drug.     

A single altered gene is only part of the disease development equation.  To be more at risk of developing a complex disease such as cardiovascular disease, an individual needs to possess a number of interactive SNP ‘faults’ in multiple genes.    A SNP that is common in one geographical region or ethnic group, may be much rarer in another.  This is one of the main arguments against using SNP based analysis for the whole population.  For example if much of the research has been carried out on a predominantly ‘pure’ Caucasian cohort the test for that particular SNP may only be appropriate for a Caucasian and not, for example an African or Asian. Navigenics SNP data is largely Caucasian, but the company is more versant in the actual calculations of life-time risk and who was included in that which may well include non-Caucasians.  Dr Nierenberg explains:  

“We have reason to believe that the data applies across ethnic groups, but further data is needed to confirm this, will be collected over time, and reported to our members. For now we are very transparent about the groups in which the studies are done, whether Caucasian or in some cases non-Caucasians. Where associations have been looked for in other ethnic groups, generally we see that the effect sizes are consistent across other ethnicities including African Americans and Asians.”

As there are estimated to be over 3 million SNPs there is obviously an infinite amount of research still to be carried out on SNPs and their interaction both at the genomic and environmental levels.  The SNP single gene model is probably too simplistic to be able to provide risk scores for complex diseases, so I asked Dr Nierenberg how Navigenics foresaw their product evolving in the future. 

Dr Nierenberg advised: “We’re not basing our entire approach per se on the test, rather we’re looking at promoting wellness and the effects of the environment on health.  We believe our members should be pointed in the right direction in terms of their genetic predisposition to disease and offered suggestions on how to manage their risk.” 

In terms of the future evolution of the product, Dr Nierenberg advises that the results of ongoing studies will be added to the core test to enhance Navigenics’ service offering.

Navigenics #4 - Low penetrance v high pentrance genes

SNPs are known as ‘low penetrance genes’ where it will only sometimes produce the symptom or trait with which it has been associated at a detectable level. In this case of low penetrance it is difficult to distinguish environmental from genetic factors.   

Whereas ‘high penetrance genes’ such as the breast cancer genes BRCA 1 and 2 are those where the trait will almost always be shown by the individual carrying the faulty gene. In this case a BRCA 1 and 2 carrier will have over an 80% chance of developing breast and/or ovarian cancer in their lifetime. 

Most high penetrance genes have been patented, in the case of BRCA 1 and 2 by Myriad Inc. It is a costly process to obtain a license from the patent owner and in the case of BRCA 1 and 2 the cost of a Myriad test is around the US $5,000 mark, two to five times more expensive than genomic screens and therefore probably prohibitive to genomic screening companies, in cost terms.   

Dr Nierenberg advises that Navigenics have made a conscious decision not to include high penetrance genes in their core panel, preferring to focus on those low penetrance genes that are affected by environmental factors.  

“In the case of the BRCA genes, only a relatively small proportion of the population – as low as 5% - carry one or more of these genes.  We are focused on SNPs that are apparent within whole populations. We make it clear in our literature that we do not test for this type of gene.”

Navigenics #5 - Corporate or pragmatic genomics

Navigenics uses Affymetrix’s gene chip which is able to test around 1 million genetic markers.  However Navigenics has initially focused on 18 specific, treatable diseases which form the foundation of its designated SNP panel.  This panel will expand over time.   

I asked the question of what happened to a member’s DNA – whether it was disposed of or stored.  Dr Nierenberg explained that a member’s DNA was stored in anticipation of future advances in understanding how genes and the environment interact in disease development.  

“As part of a member’s subscription, we will automatically advise them of these advances if relevant to their particular disease risk as and when they become available”. 

The phrases “corporate genomics” and “the Microsoft of the genome” have been coined to describe the genomic business models of companies such as Navigenics, 23andMe and deCODE Genetics where getting access to your genome would require handing it over to a company that assumes it knows better that you do which parts of your genome you are entitled to see, and then charge you again and again for updated versions of the same product.  

However, the counter argument is that from modern medicine’s inception, we have effectively handed over our health to a specialist body – physicians, who themselves have grown into corporate organisations – hospitals, who, in turn are empowered to make clinical and financial judgements on our health and well-being.  Is there really a tangible difference? 

Dr Nierenberg defends Navigenics business model by citing the very arguments that are causing deep rifts within the genetics communities, namely, Navigenics only provides members with test results for diseases where firstly there is sufficient research on the SNPs in terms of robustness of testing, clinical utility and outcomes, and secondly, but importantly, the diseases they focus on are those where something can be done to reduce the risk of developing that disease - such as exercise, nutrition and regular screening.   

Imagine the confusion and furore if Navigenics were to provide its members with their full 1 million marker analysis!  Navigenics’ (and others) sensible, if somewhat patriarchal approach of ‘drip feeding’ results to members as and when the research is robust enough to bring the SNP into the public domain, is one that should be applauded not derided.  Yes, they and others have the potential to make substantial profits if consumers chose the service.  But the corporate world is also littered with the carcasses of companies that didn’t get it right.

Navigenics #6 - Privacy, insurance, GINA and ethics

One of the main consumer concerns is that of privacy of information, both in terms that a genetic test has been undertaken but also that the results of the test are kept private and out of the public domain.  At the time of writing, the controversial GINA (Genetic Information Non-discrimination Act) is being passed by the US Senate which will enable genetic testing information to be kept private and not be used to discriminate against an individual, particularly by the insurance industry.  The insurance industry is understandable against the Bill. 

Dr Nierenberg advises that Navigenics takes the whole issue of security of data very seriously.   

“Navigenics takes precautions such as multiple servers, encryption and security audits … each member has access to their own section of the website which is password protected.  However, if a member forgets their password, there is a highly complicated route to get back in.  It is not just a case of emailing the password to an email address. … GINA legislation will be helpful in terms of protecting sensitive information”. 

The company has also incorporated a rigorous Ethics Advisory Board tasked to develop policies and report to the Executive Board in the fields of bioethics, patient rights, health information technology and technology and data security. In terms of working with the health insurance industry, Dr Nierenberg advises that at present the service Navigenics offers is ‘direct to consumer’ and the health insurance industry are not be involved.  However the company is already working with health insurers to integrate this type of testing and service as part of a standard medical insurance package. He says: 

“There is a strong health economic argument to incorporate genomic screening into an insurance package.  Catching a disease early or even preventing it must surely be in everyone’s best interests rather than wait until the disease is established and expensive treatment is almost certainly needed”. Dr Nierenberg uses the example of HIV testing and the insurance industry to describe how he believes genetic testing will evolve over time   “… Back in the 1980’s HIV testing was hated and received a lot of abuse.  However, over time the test has become familiar and everyone is comfortable with routine HIV testing”. Dr Nierenberg says Navigenics is also looking to expand it results service to become fully consumer friendly.  They are working on communication with its members via cell phone and other internet options.  However none of these initiatives can be implemented until the company is satisfied that data can be securely anonymized. 

Navigenics, at some stage, may well request permission to use a member’s DNA in anonymized research studies.  This will bring up a wealth of ethical issues such as informed consent at every stage of the research and explanation for what research the DNA will be used for.

Navigenics #7 - The barriers to success!

When founding my old company Opaldia, probably the single most challenging aspect of early adoption of genetic testing was physician barriers.  Mostly this was borne out of a genuine lack of understanding about the field of genetics but also concerns that testing was too much in its infancy and tests had not been subject to rigorous clinical evaluation.  Time and again the phrase ‘not undergone prospective trials’ was used as a defense against bringing genetic testing into mainstream medical practice. 

I was interested to learn how Navigenics proposed to overcome this barrier.  Dr Nierenberg explained that Navigenics has developed a physician education program. He says: 

“We’re developing our own on-line material but we’re working with Medscape to develop a CME program for physicians to access.  The educational material will cover a large range of information from basic to complex”. 

Dr Nierenberg describes the word genetics as a ‘hot button’, guaranteed to evoke the strongest of reactions.  He is philosophical about the fact that genetics research and genetic advances are still at a relatively embryonic stage but made the analogy with the completeness of research into the effects of smoking. 

“Everyone is aware that smoking is not good for health. Would it be of benefit to continue smoking until all the research evidence to prove smoking is bad for you is complete?  … This is the same for genetics…. If there is a means to identify an individual’s increased risk of developing a disease then isn’t it is everyone’s best interests to use this?” 

There have been a number of recent articles on the state of play of personalized genomics, some of which have been less than complimentary to industry players.  The term ‘recreational genomics’ has been used to describe these services.  I asked Dr Nierenberg whether he considered any damage had been done to this embryonic field by these articles.  Dr Nierenberg again took a philosophical view on these articles:  “Navigenics is no way a ‘recreational’ genomics company and does not wish to contemplate entering any ‘recreational’ field. It is a company focusing on the wellness and prevention aspects of health.  Our service focuses on actionable entities and things of substance such as cardiac disease, not eye colour or such like. We welcome regulation and make heavy use of genetic counseling.  We follow all NHGC latest guidelines and best practice and more …” Dr Nierenberg and his team believe that the company is ‘… ahead of the curve and when you are leading a new field there is always a level of scepticism about your service and an expectation that you will be challenged every step of the way’. He cited the example of the C-Reactive Protein (CRP) test and its use in diagnosing cardiac inflammation.  Initially the test was ridiculed but now it is established as a routine diagnostic test used alongside CT heart scanning – another modality which initially received poor press.   

Navigenics firmly believes that through educating both clinicians and the public, it will only be a matter of time before genomic screening become part of routine health and wellness programs.  By focusing its services around a serious health delivery model rather than a ‘recreational’ model, Navigenics anticipates achieving its company vision to transform medicine from a ‘sick care’ model of ‘wait and see’ to the emergence of early risk detection and prevention of disease development.

I hope you enjoyed this series of articles about Navigenics’ Wellness Services.  I am most thankful to Dr Michael Nierenberg and the Navigenics’ team for the opportunity to discuss in-depth the issues surrounding the whole field of personal genomics services, wellness and health management.

Elaine Warburton  www.geneticsandhealth.com

In this third article originating from G&H’s exclusive interview with Navigenics’ Medical Director, Dr Michael Nierenberg, we explore the whole issue of SNP testing and how SNPs can be used in disease risk assessment.

Navigenics has focused on around 100 of the most definitive research papers on SNPs (single nucleotide polymorphisms) that have been most strongly associated with 18 particular diseases such as breast cancer, type II diabetes, cardiovascular disease.  The company has built an algorithm (mathematical computer program) that estimates the risk of a healthy person developing a disease if their genome has the relevant SNP. 

The company has spent immense time and financial resources on engaging its panel of scientific and clinical experts to analyze the many hundreds of SNP association studies.  Says Dr Nierenberg:  

“It is a pre-requisite for Navigenics that any SNP to be included within its core panel must have undergone rigorous scientific and clinical evaluation and had the supporting research replicated in an appropriately peer reviewed paper. Functional data and magnitude of effect are also taken into account, but studies are not automatically excluded if functional data is unavailable or the effect estimate is small.  That being said, there is currently nothing on our panel with a relative risk less than 1.1 of developing a disease if the associated SNP is carried.”

99% of human DNA sequences are the same across the entire human population.  However, variations in DNA sequence can have a major impact on how humans respond to disease, the environment and drugs & medicines. SNPs are DNA sequences that occur when a single nucleotide (A,T,C or G) in the genome sequence is altered.  For example - AAGCT to ATGCT.  For a variation to be considered a SNP, it must occur in more than 1% of the population.  Many SNPs have no effect on cell function, but many could predispose people to disease or influence their response to a drug.     

A single altered gene is only part of the disease development equation.  To be more at risk of developing a complex disease such as cardiovascular disease, an individual needs to possess a number of interactive SNP ‘faults’ in multiple genes.   

A SNP that is common in one geographical region or ethnic group, may be much rarer in another.  This is one of the main arguments against using SNP based analysis for the whole population.  For example if much of the research has been carried out on a predominantly ‘pure’ Caucasian cohort the test for that particular SNP may only be appropriate for a Caucasian and not, for example an African or Asian. 

Navigenics SNP data is largely Caucasian, but the company is more versant in the actual calculations of life-time risk and who was included in that which may well include non-Caucasians.  Dr Nierenberg explains:  

“We have reason to believe that the data applies across ethnic groups, but further data is needed to confirm this, will be collected over time, and reported to our members. For now we are very transparent about the groups in which the studies are done, whether Caucasian or in some cases non-Caucasians. Where associations have been looked for in other ethnic groups, generally we see that the effect sizes are consistent across other ethnicities including African Americans and Asians.”

As there are estimated to be over 3 million SNPs there is obviously an infinite amount of research still to be carried out on SNPs and their interaction both at the genomic and environmental levels.  The SNP single gene model is probably too simplistic to be able to provide risk scores for complex diseases, so I asked Dr Nierenberg how Navigenics foresaw their product evolving in the future. 

Dr Nierenberg advised: “We’re not basing our entire approach per se on the test, rather we’re looking at promoting wellness and the effects of the environment on health.  We believe our members should be pointed in the right direction in terms of their genetic predisposition to disease and offered suggestions on how to manage their risk.” 

In terms of the future evolution of the product, Dr Nierenberg advises that the results of ongoing studies will be added to the core test to enhance Navigenics’ service offering.

To learn more about the company and its thoughts on key issues surrounding the genomics industry, look out for the following articles which will be posted throughout this week.

Navigenics #1 - My genes, my health, my life – who are Navigenics? 

Navigenics #2 - A stroll through your genomic park – about the test

Navigenics #4 - Low penetrance v high penetrance genes

Navigenics #5 - Corporate or pragmatic genomics

Navigenics #6 - Privacy, insurance, GINA and ethics

Navigenics #7 - The barriers to success! 

Elaine Warburton  www.geneticsandhealth.com

A research team comprising scientists from MD Anderson, Johns Hopkins University and the Insitutute for Cancer Research and the University of Cambridge, UK have identified two inherited genetic variations (SNPs) on chromosome 15 associated with increased risk of lung cancer for smokers and former smokers. Individuals who have ever smoked and who have one or two copies of either of these SNPs have increased risks ranging from 28% to 81% of developing lung cancer.

The findings are a major step forward in identifying those at high risk for non-small cell lung cancer and for understanding how smoking and genetic factors interact to cause the disease. The team’s findings might also provide support for a growing body of evidence suggesting that nicotine, long known as the prime addictive compound in cigarettes, might also play a direct causative role in the development of lung cancer.

The research team conducted a series of genome-wide association studies, first genotyping 317,498 different SNPs from 1,154 smokers who had lung cancer and 1,137 smokers without lung cancer. They then analyzed the top 10 SNPs in an additional cohort of Amercian patients and replicated the research in a cohort of 5,075 DNA samples from UK smokers with and without lung cancer and narrowed the SNPs down to two variations.

Two of the 10 SNPs were consistently associated with lung cancer risk and both of them are located in chromosome 15 inside a region that contains genes for the nicotinic acetylcholine receptor alpha subunits 3 and 5, which already are suspected to play a role in lung cancer progression.

The research team then wondered if these genetic associations relate to nicotine dependence, and found that the same two SNPs also are weakly associated with smoking behavior.

The genetic variations might help identify smokers at higher lung cancer risk who would be the best candidates for regular screening.

The study was predominantly undertaken on a Caucasian cohort to eliminate ethnic variation. A similar genome-wide study of African-American smokers is planned.

“The power of genome-wide analysis is to look at many markers and many samples at once, which can reveal weak genetic associations in complex diseases like lung cancer.”says Kimberly Doheny, Ph.D., assistant director of the Center for Inherited Disease Research at the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins.

Elaine Warburton www.geneticsandhealth.com

Icelandic company deCode Genetics has announced it has signed a Letter of Intent to offer its genetic testing products to US Preventative Medicine customers.

US Preventative Medicine is a Dallas based company. The company has developed a suite of prevention, early detection and chronic condition management products and services that improve health outcomes while reducing health care costs.  It’s products are as follows:

“The signing of the letter of intent with DeCode is significant because we will be the first entity in the US and internationally to offer a full continuum of geographically dispersed, comprehensive solutions for personalized medicine,” Christopher Fey, chairman and CEO of US Preventive Medicine, said in a statement.

Elaine Warburton www.geneticsandhealth.com

Many gene studies focus on WHICH genes cause a person’s risk of developing a disease (forward genetics) but few focus on HOW those genes can lead to disease.  Researchers at Merck and Co, deCODE genetics and academic centres in the US and France have focused on the latter and shed light on the complexity of common disease causes where multiple genetic changes are involved (functional genetics).

Two studies analysed DNA variations, patterns of gene expression in disease tissue, and clinical data on a large scale to identify which gene networks linked to metabolic disorders (a range of symptoms that are thought to cause obesity, diabetes and atherosclerosis or heart disease).

The first study on mouse livers looked at finding genes that might be linked to obesity, diabetes and heart disease.  The researchers created gene networks and located highly connected sub-networks of core genes that were known to be linked to obesity, diabetes and heart disease. They also identified, and validated at the experimental level, three new genes thought to cause obesity: Lpl, Pmp1l and Lactb.

The second study on over 1,000 human blood and fat tissue samples from Iceland, and using data from the first study, created a gene expression network of human obesity traits.  This human obesity network showed considerable overlap with the mouse network.

The researchers concluded that:

“A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.”

The next question is WHY?

Elaine Warburton  www.geneticsandhealth.com

In January, The New England Journal of Medicine published an article criticizing the popularization of genetic testing by companies such as 23andme, deCode, Navigenics and Knome who doctors believe are introducing genetic testing prematurely into a commercial setting and confusing public and medics alike.  The authors of this article coined the phrase ‘recreational genomics’ for this type of testing.

While all of these companies claim that their tests should not be used as the basis for medical decisions, some physicians are concerned that customers for these tests will nevertheless begin seeking medical direction based on their results.  Doctors have been unprepared for the genetic advice they need to give their patients. 

The British Medical Journal has also published an equally critical article on the commercialization of genetic testing written by Exeter University Professor of Epidemiology and Public Health, David Melzer, whose own interest lies in research on genetic and conventional risk factors for chronic conditions of ageing.

Among the author’s concerns, is the need for strong regulatory oversight of genetic tests, tests based on empirical evidence, and public and physician education based on sound and transparent information.

“Although major scientific progress has been made, clinical applications are still mostly unclear,” Melzer wrote.

He suggests the key value of genetic markers may be in providing clues about disease mechanisms. On the other hand, he argues that few of the current markers are useful diagnostically, particularly those associated with moderately increased risk and/or with conditions for which no preventative interventions are available.

My personal belief is that introducing innovative genetic testing technology has to start somewhere.  With genetics we will never understand 100% of the complexities and interactions between our DNA and the environment - that is for the ‘divine being’ to know.  These genomic companies have taken a huge financial and clinical risk in bringing these tests to the market.  The tests are in their infancy and each of these companies are transparent in advising their customers of this fact.  That said, massive scientific research continues to take place to build on the knowledge base of these tests, so that they may be refined.  This process will never end.

Most people are fascinated by their own health and mortality.  Millions are spent on a plethora of mainly unproven herbal drugs and vitamins that have the potential to damage an individual. Many more millions are spent on early stage gadget technology.  If an individual wishes to understand more about their genetic risk of developing a disease and testing is available then it is also their right to purchase a test.  Surely commonsense dictates that raising an individual’s awareness of their risk of developing a disease is a good thing, particularly if that individual takes control of their health and well-being by perhaps eating more sensibly and taking more exercise?

In terms of patient education and support, these genomic companies are providing some pretty in-depth advice which customers have access to.  In terms of doctors providing more information and education on genetic testing, the question needs to be asked as to why medical schools are not preparing doctors sufficiently in this area? Genetics and the knowledge of the role it will play in diagnostics has been around for a good 30 years! Genetics and genetic testing should be part of the core medical training syllabus and ongoing professional education. 

… and for that matter it also needs to be taught as part of the school syllabus.  Genetics has come along way since Gregor Mendel’s pea plant experiments in the 1850’s and yet that is still the level of subject knowledge our kids are being taught!

Elaine Warburton  www.geneticsandhealth.com

It is universally accepted that genetic testing is here to stay and will play a major role in health management.  Common sense dictates that it is good health management to understand what diseases an individual is susceptible to, so that steps can be taken, by that individual, if they so wish, to minimize the chance of developing a particular disease or diseases.  Genetic testing, although in its infancy, will eventually be robust enough to provide those answers.

DNA testing best practice requires test results to be clearly explained to patients by a suitably qualified specialist, more often than not a genetic counselor.  If a patient is at risk of a particular disease then best practice dictates that the individual should be offered a health screening program to detect any abnormalities early…. early detection improves survival.

A recent survey by The National Human Genome Research Institute observed that the number of Americans taking advantage of precautionary DNA testing appears to be going down, and the reason is thought to be fear of genetic discrimination from health insurers and employers.

Some health experts are so concerned that they have called for new legislation to protect US citizens from being discriminated against should their DNA test reveal health risks.

A bill which was passed by the House of Representatives last year and is yet to reach the Senate, the Genetic Information Nondiscrimination Act, would prohibit insurers from denying benefits or raising premiums as a results of genetic information, and it would prohibit employers from collecting or making use of genetic information for hiring, firing or compensation decisions.

Another trend that could be fuelling this concern is the rising use of home test kits for DNA. You send a DNA sample to a private service that sends the results directly to you, without your doctor or anyone else knowing about it.

There are advantages and disadvantages to this. On the one hand, it gives people increasing control over their own medical data, but on the other hand, if people want help, but are frightened of the consequences, it could develop into a public health crisis with people denying themselves prompt care and not revealing conditions until symptoms have progressed.

In a recent article, commenting on these latest findings, The New York Times reports experts saying that the benefits of the increasingly personalized approach to health care are being lost because Americans are too afraid of the potential consequences to take advantage of it. Doctors say people can make better informed decisions about their health if they know what risk factors they may have inherited, for instance breast cancer or colon cancer, but this advantage is lost if they fear the consequences will leave them worse off financially.

Whether discrimination actually occurs or not is not the issue, say some health experts, because the anxiety is what needs to be addressed and the sooner the legislation is put in place to protect citizens the better. Dr Kenneth Offit, chief of the clinical genetics service at the Memorial Sloan-Kettering Cancer Center in New York, said fear of genetic discrimination was the main reason people were cancelling appointments to find out if they had cancer risks:

“It’s a tragedy that people are being scared off by this,”said Offit, “we are dealing with potential lifesaving interventions”.

Elaine Warburton  www.geneticsandhealth.com