23-not-for-me: My thoughts on direct-to-consumer genetic testing

As a geneticist, I’ve been studying the genomes and genetics of other individuals (and species) for years now. From time to time, I have been curious about learning about my own genome. What’s hidden in the base pairs of my DNA sequence and what does it say about me? Do I really want to know? What would I do with that information if I had it?

Now, anyone who’s willing to fork out $99* can get their genetic information easily through companies like 23andme. If you haven’t heard of 23andme yet, you will as they’re now advertising on television. It works like this: you spit in a tube and a month or so later, you find out if you carry genetic variants in your DNA that may be associated with increased risk for certain diseases, may affect your response to certain drugs or a number of other traits. You also find out information about your ancestry.

Just to be clear, you don’t find out the sequence of your entire 3 billion base-pair genome. You get sequence information for about 1 million sites that are known to vary among individuals (called Single Nucleotide Polymorphisms or SNPs, pronounced ‘snips’) and have been studied for association with various phenotypes (things we can detect in people, like physical traits or health conditions, that are a result of genetics or genotypes).

That sounds like a lot of data. And I love data!

So, am I going to spit in a tube and wait for my own genetic data?

I don’t think so! At least, not yet.

The major reason is that we have limited information to really understand the impact of different variants. Yes, we’ve been able to identify a lot of variation among humans and, yes, we’ve even done studies that link certain variants with an elevated risk for common health problems like diabetes and heart disease. But most of these studies show weak associations with modestly elevated risk of disease.

With a few exceptions, there is very little actionable information that one can learn beyond current recommendations for a healthy lifestyle. What would the recommendation be for someone who carries a variant that’s associated with elevated risk for diabetes or heart disease? The answer: healthy diet and exercise. What’s the recommendation for the general population to reduce risk of diabetes and heart disease ? The answer: healthy diet and exercise. And what if you find out that you’re not at risk for heart disease or diabetes based on the variants that were tested, does that mean you won’t get heart disease or diabetes? No, not necessarily! So how much does knowing you have these low impact variants actually help?

Let’s talk about data again. It is a lot of data. But is it enough? If the genetic testing tells you that you don’t have the variants that put you at risk for breast cancer, are you really safe? Having worked in this field, I know that there are literally thousands of mutations across tens of genes (that we know of so far) that can put you at risk for breast cancer. A negative result from a few variants tested in such tests may give someone with family history of breast cancer a false impression that they are ‘safe’ from the disease.

A big concern is that, for some folks, this kind of testing (direct-to-consumer) may take the place of traditional genetic testing which is done under the guidance of a physician and a genetic counselor, who can better interpret and explain risk of disease. Based on your family history, your physician and genetic counselor can determine if you need to get genetic testing done for disorders known to have strong genetic basis (like predisposition to breast cancer or Huntington’s disease). I would argue that knowing and informing your physician of your family history is paramount.

So what about you? Should you send away spit for your genetic information?

Sure, if you want. But, I would think of it mostly as entertainment only (for now). It could be fun to find out about your ancestral genetic background. My own family history can be traced back for a few hundred years but I might be curious to see who my ancestors were further back in time. And, one may argue that gathering genetic data from a large number of individuals may actually help us better understand impact of genetic variants. But as far as I know, there’s no medical history or medical tracking that’s associated with your genetic information, which would be needed those kinds of studies.

Bottom line, if you decide to fork out a hundred bucks, just be informed about how much weight to put in the information you get. I wouldn’t base any major health decisions based only on these sorts of tests. Personally, I would wait until there’s more information available that will help us better understand the impact of genetic variants that contribute modestly to disease states. And if you suspect you may carry a disease-causing mutation based on family history–talk to your doctor!

*Actual cost can vary depending on how long you want access to the data. The cost of the kit and testing is $99.

Why should you care about science?

And why should scientists care if the general public cares about science?

Last week I wrote about the importance of science community engagement in public education and the role of science journalism. The implicit assumption of the post is that it is important for the general public to be engaged in science. In case you don’t share this assumption, let me outline a few reasons why you should.

  • Scientific developments affect us all, whether it’s the development of new cancer therapies, understanding what causes drug resistance in ‘super bug’ bacteria, or evaluating the safety of genetically modified foods (we all consume them).
  • Having a better understanding of how seemingly small contributions in very specialized areas by a large number of scientists (which includes some disagreements), over time and across the world , collectively help fields move forward will help the public understand why science is slow.
  • A general public that understands how discoveries in a fruit flies or yeast can help human health and innovation in general will hopefully generate more support for research. Public support for research may translate to an increase in funding.
  • Beyond financial support, an informed general public can better judge science news without the sway of politics (think global warming).

As you can see, the benefits are many for both scientists and non-scientists alike!

It’s not my job . . . or is it?

Recently I had the privilege of meeting Joe Palca, a science correspondent for NPR and creater of Joe’s Big Idea. I had invited Joe to come speak to young scientists at our institution about science writing. In addition to picking Joe’s brain for career advice, this was an opportunity for us to learn more about science reporting. Most scientists will tell you they feel that main stream media science stories leave out important details and often misrepresent the impact of scientific findings.

Joe, who has a PhD in sleep psychology from UCSC, seemed like the perfect person to have this conversation with since he knows the worlds of science and journalism well. I expected him to echo some of our frustrations and maybe vent about limitations of reporting to a general public that has a limited science education or gripe about colleagues who don’t pay attention to detail. To my surprise, the conversation went in a very different direction. When asked if Joe feels like it’s his (and other science journalists’) responsibility to educate the public about science, he responded “no” and said that his responsibility was to report on science, which is different.  He pointed out that most science reporting pieces usually have no more than one or two sentences actually describing the science—the story is often about the people doing the science, not the science itself. This was a surprising and interesting perspective to hear. Thinking more about this, Joe’s right. He’s a journalist, not an educator. His job is to report on the story. Why do we as scientist place the burden for educating the public on the shoulders of journalist?

If it isn’t Joe’s job to educate the public, whose job is it? Regional and national science education centers like the Pacific Science Center in Seattle do a great job of educating some of the public. But can we, as scientists in the trenches, do more? I think we can. And we should. Most science in this country is funded by the government which means tax payer money. We routinely give progress reports in the form of scientific publications to the scientific community, but isn’t it our job to give a progress report to the taxpayer as well? Having said that, I do concede this is a really difficult task. Most of us are great at presenting our most recent findings in auditoriums full of experts but when it comes to explaining what we do to grandma, we can find ourselves at a loss for words!

Science makes it into the news if there’s a huge discovery in a particular field. But, there’s a lot of cool science going on all the time! I know because my friends are work on it—human evolution, anti-freeze proteins, genetic engineering, just to name a few. Now, let’s see if we can find a way to tell you about it. Stay tuned!

FHCRC scientists meet with Joe Palca, NPR Reporter
FHCRC scientists meet with Joe Palca, NPR Reporter

Photo: By Philamer Calses, University of Washington PhD Candidate

Message from a princess: Cancer is a global health problem

When I think of global health issues pertinent to the developing world, I generally think of infectious diseases–like malaria, HIV and tuberculosis. Cancer usually doesn’t come to mind–it’s only a problem for the developed world, right? Wrong.

After attending a lecture today by Her Royal Highness Princess Dina Mired of Jordan (King Hussein Cancer Foundation), it is clear to me that cancer is a global health problem. The lecture also included remarks by  Dr. Julie Gralow (Seattle Cancer Care Alliance oncologist and Jill Bennett Endowed Professor in Breast Cancer), Dr. Julio Frenk, (Dean, Harvard School of Public Health and former Health Minister of Mexico) and Dr. Felicia Knaul (Harvard Medical School). It turns out that about 54% of cancer diagnoses and 64% of cancer deaths in the world come from developing countries. By 2030, the percentage cancer deaths that come from developing countries is predicted to go up to 70%. What’s tragic is that many of these deaths are preventable! For example, Acute Lymphoblastic Leukemia has 80-90% survival rate in the western world, while the survival rate in developing countries is around 10%.

CANCER IN DEV

Another example is cervical cancer. While cervical cancer related mortality has gone down in the US due to extensive screening, it still a major problem in developing countries. Several years ago, scientists (including some who work across the hall from me) developed a vaccine that prevents a vast majority of cervical cancer by targeting the Human papilloma virus (HPV). HPV infection is the leading cause of cervical cancer. A recent study (written about in the New York Times today) shows that the incidence of HPV infection has significantly decreased in teenagers since the introduction of the HPV vaccine. This is great news for the US as we can also expect rates of cervical cancer to go down. But what about poorer countries? Under the direction of Dr. Julio Frenk, Mexico has implemented health reforms that provide the HPV vaccine free to school-aged girls. This practice is not widespread in most low and mid-income countries though it can help prevent cervical cancer.

Additionally, a fact of life with cancer often is the necessity for palliative care–end of life care that generally involves management of pain. While availability of medicines to manage pain is good in the US, Canada, Australia and the EU, it is a huge problem in developing countries. Sadly, not only will more people die of cancer in developing countries but they will likely die in more pain.

What are the reasons for these disparities?
One obvious reason is access to healthcare facilities that can provide the appropriate care–especially in rural settings. More than just facilities, many places lack well-trained oncologist and other professionals. Princess Dina Mired pointed out that many developing countries send students to the West for studies, but few come back to practice medicine in their home countries for various reasons. Even for patients who have access to healthcare and trained providers, paying for the treatment is problematic. The lecturers today cited that prior to health reforms in Mexico, almost 30% of breast cancer patients never finished cancer therapy (for which their families had already gone into severe debt) because they ran out of money. Of course, financial strain as  result of expensive treatment even with insurance can also be a problem here in the US.

There is also a divide in global funding of programs to eradicate infectious diseases vs those that target cancer in developing countries. The Bill and Melinda Gates Foundation and others have made a commendable and effective push to improve survival from infectious diseases. But why has cancer in developing countries been largely ignored by the folks holding the money bags? Perhaps it is because of the myth, which I was guilty of believing, that cancer is only a problem for wealthy countries. I hope the some of the numbers I provided above will convince you this is simply not true.

How do we overcome these disparities to reduce cancer incidence and improve cancer survival in developing countries?
Obvious solutions are improve access to health care, have better trained staff and good equipment, make health care affordable, and get more people to invest in cancer prevention and treatment for developing countries.

So, how do we do that?

What are your solutions?

 

 

References and suggested reading:
*Saving the Children — Improving Childhood Cancer Treatment in Developing Countries
Blog by Dr. Felicia Knaul
FHCRC Petri Dish blog post on HPV vaccine efficacy

Finally understanding the impact of sequestration

“How has sequestration affected you and other postdocs?” a journalist asked me a few weeks ago. He was doing a story on the impact on scientific research of this year’s $85 billion reduction of federal spending. The vast majority of scientific research in the United States is funded by the federal government.

To be honest, I wasn’t really sure how to answer his question. I happen to work at a world-class cancer research center that has been able to provide an incredibly supportive environment for research, even during the financial downfall of 2008. I figured we’d be ok for now. The future, however, is less certain.

A likely direct impact of sequester is that fewer scientists may choose to go into academia. Colleagues who are hoping to have careers in research at academic institutions are worried since it’s becoming more and more difficult to get research grants funded. The funding situation was already pretty tough before sequester. The question on everyone’s minds is how will it change now? Academic career pursuits are also in trouble due to the fact that university departments may also slow down hiring of faculty. In the current climate, PhDs may choose to explore other science-related fields—biotech, science writing, consulting, to name a few. How these non-academic sectors handle the potential increase in PhDs being funneled towards them remains to be seen.

As PhDs in the US, how are we going to train ourselves for nonacademic careers with limited resources? As graduate students and postdocs in academic institutions, we’re generally trained to do one thing: how to do academic research. We can choose to take part in extracurricular activities that do train us for the non-academic job market. The extent of this training and participation varies from institution to institution. Luckily, I work in a place where there is a lot of institutional support (financial and administrative) for such programs. We probably have one of the best* student and postdoc associations in the nation but our budget has taken substantial hits several times this year. Going forward, we’ll have to think hard about the kinds of career development programs we can offer and become more creative with our resources. I feel deeply for my colleagues at other institutions who are starting or trying to maintain programs with almost nonexistent institutional support.

There are likely to be broader impacts on science in the US. Our commitment to scientific progress has played a huge role in the amount of innovation that comes out of the US—and this very innovation (and our immigrant history) is what has made us a global leader. (It sounds cheesy, but I believe in this strongly.) I worry that this will change if we don’t continue our commitment to science. This problem is bigger than this year’s sequester. Rates at which research grants are funded have been steadily decreasing over the last decade.

These were the issues as I understood them at the time of the interview when I shared them with the reporter. I now know that my understanding of the impact of sequestration on science was far from complete. I hadn’t considered the impact on people—not just careers.

The main function of a research center is, of course, to support and carry out research. In order to preserve funding for this essential function, difficult decisions have to be made to reduce the number of support staff (administrative, technical, etc). This happens at the level of research centers and in individual labs. Saying goodbye to these valued colleagues is when I finally understood the impact of sequestration.

 

*Ok, as chair of the said association, I might be slightly biased. The assertion as to the strength of our program is based on my experience at a recent national conference, where I had the chance to compare ours with other organizations.

Angelina Jolie’s Story—An Incomplete Picture

In an op-ed piece in The New York Times, actress and director Angeline Jolie wrote that she recently had a prophylactic double-mastectomy to reduce the chances of developing breast cancer, a disease that took her mother’s life. She explained that she carried a “’faulty’ gene, BRCA1” which puts her at high risk for developing breast and ovarian cancer. She underwent the double mastectomy to reduce the risk of breast cancer by removing the tissues that generally give rise to tumors.

I heartily applaud Jolie’s documentation of a very personal experience on such a public platform in an attempt to encourage women with family history of breast and ovarian (and other) cancers to have open discussions with their medical professionals about genetic testing and possible preventative options that may be available to them. I can’t stress how important it is to have open conversations about scary health issues like breast cancer, especially since they may be tied with health, identity and possibly sexuality.

However, I must admit that as a scientist who studies BRCA1-associated breast cancer, I also felt a sense of alarm as I read the article. Many thoughts whirled in my head. Jolie’s focus on primarily breast cancer in women with BRCA1-mutations and double-mastectomy as a preventative option is far from complete. Though I respect Jolie for speaking openly about her personal matter, I feel that she and others who speak on such matters in public platforms have a responsibility to make the discussion as close to complete as possible. As a person of great influence, I wish she had provided a more complete picture, especially to a world in which medical and scientific information is often presented over-simplified to the brink of being inaccurate (more on this in another blog).

Below I attempt to touch on a few of the issues and questions that were largely ignored in Jolie’s piece.

Is it really that simple?

The article suggests that it’s quite straightforward: Everyone can go get tested for BRCA1 mutations and if positive for a mutation, can get a double-mastectomy and they’re cancer free! Let’s ignore for the moment that mutations in BRCA2, and a growing number of genes involved in similar cellular pathways, also lead to increased breast cancer risk. It also implies that mastectomy is the only preventative option available. Generally, women with family history or with known BRCA mutation are followed closely to allow early detection (and treatment) of breast cancer though they tend to have slightly higher risk of breast cancer (a yearly incidence of 2.5%) than those who have undergone prophylactic mastectomies (Meijers-Heijboer et al). Other, less invasive, options exist.

What is the impact on healthcare and more?

How many women without family history of cancer will visit their physicians and demand testing for BRCA? As Jolie mentions, the current cost of genetic testing for genes for breast cancer predisposition is over $3000. It is currently recommended for individuals who have family history of breast and ovarian cancer (and sometimes others) to have genetic testing to look for disease causing mutations and insurance generally covers this cost. We must think about the general impact on the cost of healthcare more broad genetic testing will have (at current costs), without even considering the cost of additional doctors’ visits by individuals at low-risk.

Another complication is what is known in the BRCA research and clinical community as ‘Variants of Unknown Significance’ or VUS. VUS refers to ‘mutations’ in BRCA1 that may just be changes in the gene that are not known to lead to cancer. We all carry differences in our genetic code in many of our genes compared to others in the human population. Many of these changes are benign—they don’t have any perceivable effect on our biology and health. We usually refer to changes in our genetic code that do have a perceivable effect on our health as ‘mutations.’ It is unclear whether a lot of the changes that are known to exist for BRCA are benign or real mutations. We must consider the potential scenario of a nervous individual with a benign VUS deciding to undergo major surgery like prophylactic mastectomy or oophorectomy (see below). Is the benefit in this case worth the physical, emotional and financial costs?

What about the ovarian cancer risk?

Discussing breast cancer (and preventative mastectomy) without a thorough mention of ovarian cancer for BRCA1-mutation carriers is an incomplete discussion. Jolie briefly touches on ovarian cancer risk; she does not provide it the weight it deserves. Granted I may have a biased perspective as a breast cancer researcher, I don’t perceive education on breast cancer in the US to be lacking. We are constantly inundated with emails, media campaigns, professional sports stars wearing pink athletic shoes, among other things that bring awareness to the real dangers of breast cancer. We have many options (with varying degrees of effectiveness) for early detection of breast cancer.

Ovarian cancer is a different beast. One of the biggest problems with ovarian cancer is that it is often not detected until it is progressed to an advanced stage. Chemotherapy and surgery are among the treatment options that can increase survival but the prognosis is generally not great, 5-year survival rates of 18-35% for aggressive, late-stage disease (American Cancer Society). For individuals with advanced risk, like BRCA1 mutation-carriers, prophylactic oophorectomy (preventative removal of the ovaries), which can accompany removal of other organs like fallopian tubes, is an option. But, it’s complicated. It’s a difficult decision since it can affect when a woman has children and has many long-term health complications including hormonal changes, increased risk for osteoporosis and cardiovascular disease. Furthermore, risk of ovarian cancer after surgery is lowered not eliminated.

I thank Angelina Jolie for sharing her personal story with women and opening up conversation about genetic testing for women at high risk. The story is much, much more complicated. It is imperative that those who have the knowledge and the platform inform the public in the most thorough way possible.

References

American Cancer Society: http://www.cancer.org

Meijers-Heijboer, H., et al. (2001) Breast cancer after prophylactic bilateral mastectomy in women with BRCA1 or BRCA2 mutation. The New England Journal of Medicine, 345 (3): 159-164.