My Inner Geek Takes Over

Genetic Testing: The ultimate TMI

My inner geek took over and wrote this way-too-long post that only a true geek (and not all of those) would want to read. However, if you want to know where I got my facts and read the original sources for the user-friendly version that comes after (above) this one, READ ON!

In 2008, TIME Magazine rated the The Retail DNA Test as the #1 Best Invention of the Year. On January 11, 2011, 23andMe.com released its list of the “”Top Ten Most Interesting Genetic Findings of 2010”, a list that ranges from new information on the risks for Alzheimer’s, arthritis and asthma to our relationship to Neanderthals.

How much information about your health/future health do you really want to know?

Genetic testing gives us both too much information (TMI) and too little. While some people want to know more, others would choose not to know, though the information could affect current life events, lifestyle decisions or future planning. Even someone as closely involved as genetics pioneer Dr. James Watson, the first individual to have his complete genome sequenced in 2007 (at a cost of approx. $1 million), chose not to be told of his personal risk for developing Alzheimer’s Disease (AD).

Harvard Psychologist Steven Pinker, another of the first ten to be sequenced, says, “People who have grown up with the democratization of information will not tolerate paternalistic regulations that keep them from their own genomes, and early adopters will explore how this new information can best be used to manage our health.” All the same, he asked for a “line-item veto” of his APOE information, a gene associated with Alzheimer’s risk.

In fact, we may be more interested in contributing to scientific knowledge and finding out more about our own genetic data than we are concerned about the potential risks or misuse of our data. Americans in general (4 out of 5) “…support the idea of a nationwide study to investigate the interactions of genes, environment and lifestyle, and three in five say they would be willing to take part in such a study. Joan Scott, director of the Genetics & Public Policy Center at Johns Hopkins University who released the study put it this way, “It’s me, it’s my genome. And I want to know about me.” A fair number of testers have been willing to post some of their genetic data online. With the exception of his Alzheimer’s gene, Steven Pinker says you can google his genome (I didn’t find the actual genome). He and the other nine have released their data to the public through Harvard Medical School’s Public Genome Project (PGP).

The dilemma is inherent in the information.

Current knowledge paints a narrow picture of what we can know with certainty. Our genetic code answers some questions with near certainty:Will I develop Huntington’s Disease (HD); Does my child have Down Syndrome ? It answers others with probabilities, risks and unknowns that interact with other factors such as lifestyle and environment, making an individual’s future much more difficult to predict.

The human genome consists of 23 pairs of chromosomes containing our DNA, 50% of which we share with a banana, 70% with a slug and 99.5% with every other human being. On these 23 paired chromosomes, our 3 billion base pairs replicate, though not always perfectly. When a piece of a base pair varies (left out, added or substituted) from the pattern, it creates a single nucleotide polymorphism or SNP. Our genome contains approximately 10 million of these SNPs which hold the key to genetic differences between us. A complete genome sequence looks at everything, indirect DNA testing looks at the SNPs, DNA sequences where most of the differences lie. 23andMe collects data on one million SNPs though we don’t know what differences every SNP determines. We may know some of the BRCA (breast cancer) mutations, but not all of them. We may know some SNPs that confer added risk for a specific disease – but not those that add a protective effect. It is easy to understand how difficult it is to interpret – and act on – such incomplete information.

The scientific/medical community generally recommends NOT testing individuals without symptoms or giving out specific information on a person’s risk of developing AD. The rationale is that in those diseases or conditions where there is no guaranteed prevention or cure, the knowledge is likely to be more of a burden than a help to the person and their family. As one counselor said, “So much of our counseling is looking at weighing the risk versus the benefit, the value of knowing, the motivation for knowing. Because once I give you the test results, once you have your answer, you no longer have the option of not knowing. I can’t take it back.” (Italics mine)

On the other hand…Hank Greely from the Stanford Law Center for Law and BioSciences suggests, ”You should not be very worried about what you find out – as long as you realize that it is almost always useless. “ Read the full post to do it justice, – he does note worthy exceptions!

Most women who get breast cancer do not have a BRCA gene mutation, “As many as 95 out of 100 women who get breast cancer don’t have them, so a BRCA test might not help you identify your risks” Not only do most women with breast/ovarian cancer not have the mutation, about 40% of those who do – don’t get breast cancer, and up to 85% – don’t get ovarian cancer.

A study published in the New England Journal of Medicine notes that “The uncertain clinical validity and utility of genomewide testing also suggest that screening decisions that are based on the results of such tests may be ill considered… The data from these tests provide highly limited information, since they are derived from genomewide association studies that have yielded variants accounting in most cases for less than 10% of the heritability of the diseases studied.” A valid concern – unless you already have reason to be concerned due to personal or family history.

The quality of the testing is not in doubt.

In a post on Genomes Unzipped, “Should you trust a genome scan?” Daniel McArthur says:

“For reputable genetic testing companies – and I would count the four major personal genomics companies (23andMe, deCODEme, Navigenics and Pathway Genomics) in this category – the first step is generally extremely accurate. These companies rely on the same technology used by academic researchers studying the genetic basis of human disease, applied in carefully quality-controlled labs, so their error rate is typically very low. As an illustration, I recently had an opportunity to compare the raw genetic data provided by two companies to Times journalist Mark Henderson, and found an error rate per company of around one in every 14,000 data points: that’s far better than most routine clinical tests.”  Antonio CB Oliveira wrote a computer program to compare his personal results from two companies, 23andMe and deCODEme and found only 23 cases out of 560,299 SNPs in which the results do not agree.

The difficulty is in the interpretation of the results.

Without a qualified genetic counselor, not to mention a pretty high level understanding of statistics and probability, interpreting your results is difficult and limited by your access to the kind of scientific information necessary to correctly interpret data. If you go through a doctor to order your tests, you will almost certainly receive your results in the context of genetic counseling. If you order online, as I have, you will receive most of your raw data and some help with interpretation; companies like 23andMe are very careful to state the limits of their services when it comes to interpretation or diagnosis. You can uploaded your raw data to Snpedia.com and get a more nuanced report, again, without the services of a genetic counselor.

The fear is how we will respond to the knowledge.

In the early days of genetic testing, there was considerable debate on how individuals and their families might respond to the information, particularly if it was “negative”.

“Proponents argue that providing this type of information directly to consumers may result in improved compliance with health-screening practices and more healthful lifestyle choices. Skeptics assert that such testing has the potential to cause harm, including anxiety and increased use of unnecessary and expensive screening and medical procedures.”

Research published just this month (Jan. 2011) in the New England Journal of Medicine is showing no significant negative results and some positives.

“We found no evidence that learning the results of genomic risk testing had any short-term psychological, behavioral, or clinical effects on the study subjects. The subjects in our study are probably representative of the current population of persons who purchase these tests, although they probably are not representative of the population at large.

Among the preliminary results:

  • Only 10% reported speaking with a genetic counselor
  • 26% shared their results with their doctor
  • There were no significant associations between composite measures of risk and follow-up scores on anxiety level, dietary fat intake, and exercise behavior
  • There were significant associations between composite measures of risk and the total number of screening tests that subjects intended to complete with greater frequency after genetic testing.
  • There was no significant association between composite measures of risk and the total number of screening tests actually completed after genetic testing.

In other words, though participants reported good intentions, short-term results have not shown significant follow through. However, this is a long-term (20-yr) study and results may change over time. It appears the benefit of finding out your genetic risk factors primarily rests with you – what will you do with the results? Given that the most basic actions one can take to reduce disease risks are already known (diet, exercise, weight), the question remains: Does knowing one’s risk is higher change behavior – or not?

Harvard Psychologist Steven Pinker summed it up when he said,

“As it turns out, we know what happens to people who do get the worst news. According to preliminary findings by the epidemiologist Robert C. Green, they don’t sink into despair or throw themselves off bridges; they handle it perfectly well. This should not be terribly surprising. All of us already live with the knowledge that we have the fatal genetic condition called mortality, and most of us cope using some combination of denial, resignation and religion.”

Can the knowledge be used against me?

A major concern has been the potential use of genetic information to deny employment or health care benefits to those who have chosen to test and disclosed their genetic information.

In 2001, Burlington Northern Sante Fe Railroad performed genetic tests on 35 employees suffering from work-related carpal tunnel syndrome without their knowledge or consent. They tested for a rare genetic condition, hereditary peripheral neuropathy, with carpal tunnel syndrome as one of its symptoms. An employee who realized what was happening and declined to test, was threatened with dismissal for insubordination. This case became a ground-breaking law suit charging the company with violating the Americans with Disabilities Act. The case was settled by Equal Employment Opportunity Commission in 2001 in favor of the employees.

In 2008, President Bush signed a new federal law, the Genetic Information Non-discrimination Act, providing significant protections to those who test.

The Genetic Information Nondiscrimination Act of 2008, also referred to as GINA, is a new federal law that protects Americans from being treated unfairly because of differences in their DNA that may affect their health. The new law prevents discrimination from health insurers and employers.

Note: The law does not prevent discrimination in life insurance, disability insurance, and long-term care insurance based on DNA information.

Even with the protections of GINA, an employer may have access to some genetic information they have gained accidentally, from public sources (you put it on your blog?), family medical history gained through voluntary disclosure, or genetic information required on a Family Medical Leave Act (FMLA) application. However, it is still illegal for them to discriminate based on such information or information acquired about a family member.

Genetic Engineering

In December, New Scientist revealed a breakthrough by Dr. Dennis Lo at the Chinese University of Hong Kong, making it possible to sequence the entire genome of a fetus from a blood sample of the mother. “Now, through a combination of brute-force DNA sequencing and sophisticated bioinformatics, his team has shown that it should be possible to detect any genetic disease from a sample of a pregnant woman’s blood.”

An article in TIME Healthland asks “What if new tests for Down syndrome could one day mean no more affected babies are born? Is that cause to celebrate medical advances or reason to worry we are callously weeding out the less-than-perfect in our midst? “ Among women who test and receive a positive diagnosis of Down s, up to 90% choose to end the pregnancy. At this point, most women do not have an amnio or other test to detect Down’s. If a new, cost-effective test is mass marketed, some fear an increase in elective abortions in affected pregnancies.

Since the 1990′s it has been possible for prospective parents to test their fertilized embryos and choose which to implant. The technique, called preimplantation genetic diagnosis (PGD), is primarily used when couples have a risk of transmitting a specific inherited disorder or to test IVF embryos before implantation to increase the chances of a successful pregnancy. It can also be used to ensure producing a child who can donate cord blood, bone marrow or an “extra” kidney to save a sibling.

Joe Fletcher bristles when people accuse him and his wife of trying to play God. “We watch the doctors in the hospital playing God every three weeks,” (when their son, suffering from Diamond-Blackfan anemia receives a transfusion). “If some people think they’re playing God, so be it.”

A religious perspective

Not everyone believes the avoidance of suffering is always the highest good. John H. Evans of The University of California summarizes his research on “Religious Belief, Perceptions of Human Suffering, and Support for Reproductive Genetic Technology”:

“The opponents of these technologies are largely religious groups, a fact that leads to the question of why religious groups would be more opposed to these technologies than others. Since all of these technologies are justified by their ability to relieve suffering of some kind, it is hypothesized that the actively religious have a notion of suffering different from that of advocates for these technologies, and this different notion of suffering leads to opposition to the technologies. …I find that the religiously active do have views of suffering that are distinct from the medical consensus, and these views are related to people’s conclusions about the advisability of reproductive genetic technologies.” (Full text unavailable without subscription.)

An article on Campus Crusade for Christ’s Leadership University website explains one Christian perspective on suffering. You need to read the full article to do it justice, the author is not against genetic testing per se.

“From a Judeo-Christian perspective, suffering is not the great scandal that the naturalistic worldview makes it out to be. In fact, suffering has a purpose. The Bible tells us that we are perfected in our suffering. This is a hard and rather unpopular teaching for present day American culture. To understand it better, we have to more clearly define suffering. Suffering can be grouped into two broad categories, planned and unplanned. We have little trouble with planned suffering. This is the sort of suffering that is needed to accomplish a goal. This suffering is considered worthwhile because of the reward on the other side. Examples could be going to medical school, training for a sport, or painting a house. However, we have serious problems with unplanned suffering. This suffering comes without our choice and is harder to deal with. Yet, when emerging through this suffering, we are often times strengthened and enriched.

…I do not mean to trivialize suffering. It is real, and it hurts. But focusing on our own suffering is not our purpose. To be certain, we are called to try to reduce suffering in this world. But our primary goal and highest priority should not be to reduce our own suffering. How can we possibly persevere? The Judeo-Christian perspective is an eternal perspective. Our present suffering is transient. Glory is eternal. Paul writes, “I consider that our present sufferings are not worth comparing to the glory that will be revealed in us”. Romans 8:18″

Having been through the kind of situation (the birth/death of a severely disabled child) often used as an example of the best use, (or misuse), of genetic testing, I have my own “philosophy” and religious beliefs on the place of suffering in the Christian life. My point in including this article is not to articulate my own philosophy or to advocate what yours should be, but simply to offer one religious perspective among all of the scientific data in this post!

Making the decision to test.

Misha Angrist, Professor at Duke University Institute for Genome Sciences & Policy says, “The ideal personal-genomics user is curious about the science, recognizes much of its tentativeness, and is an information seeker such that she won’t shy away from information that may not bode well for her future health.”

“…the Coriell study provides a glimpse into the motivations of the current crop of casual genetics consumers. …mostly white, highly educated, and very curious. “They’re science geeks.”

My Data:

I understand that, while I will get some very interesting information, it may not be as definitive as I would like. It may still leave me – and my family – up in the air regarding our risks for breast and ovarian cancer. I’m not sure what actions I would be willing to take, given a known risk. I do know I’ve already changed some dietary habits (more soy, less dairy) and I try to eat more anti-angiogenesis foods.

I’ve decided to ask my immediate and extended family which of my results they want to know – and only tell them what they want to know. I will share some results online, but only if they do not compromise other family members. Surely – there will still be some interesting results to share!

To end, I can do no better than Steven Pinker:

“So if you are bitten by scientific or personal curiosity and can think in probabilities, by all means enjoy the fruits of personal genomics. But if you want to know if you are risk for high cholesterol, have your cholesterol measured; if you want ot know whether you are good at math, take a math test. And if you really want to know yourself (and this will be the test of how much you do), consider the suggestion of François La Rochefoucauld: “Our enemies’ opinion of us comes closer to the truth than our own.”

Resources:

If you, like me and many others who choose to test, are curious, a “science geek”, or have specific concerns because of your family medical history, here are some resources to help you make that decision and find a provider.

23andMe.com’s list of what they test for: https://www.23andme.com/health/all/

23andme.com has a primer on genetics that I found helpful. (https://www.23andme.com/gen101/)

Begin by creating My Family Health Portrait using this tool from the Surgeon General of the United States. (https://familyhistory.hhs.gov/fhh-web/home.action)

http://www.geneticalliance.org/publications for a wide variety of family-friendly publications, including an online, customizable resource, Does it run in the Family? (http://www.doesitruninthefamily.com/)

The National Society of Genetic Counsellors (www.nsgc.org) recommends asking Five Questions:

http://www.nsgc.org/Portals/0/Press%20Releases/N80423%20Five%20Questions%20News%20Release_FINAL.pdf when making the decision:

  • Is the correct test being ordered?
  • How valid are the test results?
  • What decisions might you need or want to make once you know the results?
  • What are the credentials of the person who will give you the test results?
  • Once you have the results, what are your next steps?

Genetic Testing for Breast and Ovarian Cancer Risk: It’s Your Choice Available online or as downloadable pdf (http://www.cancer.gov/cancertopics/genetic-testing-for-breast-and-ovarian-cancer-risk/pdf) (http://www.cancer.gov/cancertopics/genetics/genetic-testing-for-breast-and-ovarian-cancer-risk)

The National Cancer Institute (www.cancer.gov) suggests one consider carefully:

  • The limits of the test
  • The advantages and disadvantages of the test
  • Would knowing this information cause me to make changes in my medical care?

Besides information on breast and ovarian cancer risks, the full article includes several excellent points to consider which are more broadly applicable for cancer risk assessment. There is an excellent list of questions to ask your medical provider (doctor, nurse or genetic counselor) as well as questions to help you consider the impact on your family – you do share 50% of your DNA with your first degree (parents, siblings, children) relatives after all. They may not want to know…or, as Robin Maratz Henig said, “If my daughter did get tested, and did have the PKD gene, then I would by default have found out something I had already decided I did not want to know: that I had the gene too, since the only way she could have gotten it was from me.” (http://www.nasw.org/users/robinhenig/gene_testing.htm)

Genetics Home Reference: Your guide to understanding genetic information” is an excellent, illustrated handbook to download or print (147 pgs). (http://ghr.nlm.nih.gov/handbook)

Frequently Asked Questions About Genetic Testing” from the National Human Genome Research Institute (http://www.genome.gov/19516567)

The National Center for Biotechnical Information Laboratory Directoy is searchable by disease, laboratory (name or director’s name) and geographic (international) location.

(http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab?db=genetests)

Genome: The future is now OPEN Documentary on the Personal Genome Project (http://thepersonalgenome.com/category/pgp/)

GINA full text: http://thomas.loc.gov/cgi-bin/bdquery/z?d110:HR00493:

http://www.ginahelp.org/GINA_you.pdf.

http://www.genome.gov/10002077

TED talk on eating to starve cancer: http://www.ted.com/talks/lang/eng/william_li.html

My Genome, Myself by Steven Pinker (http://www.nytimes.com/2009/01/11/magazine/11Genome-t.html?pagewanted=all)

www.snpedia.com builds a free report based on your uploaded SNP data.

A Family Diagnosis/In the Family Clips from a PBS documentary video of the women in one family’s decision to test for BRCA and their results.

(http://www.youtube.com/watch?v=U49KunIxVQI)

(http://www.youtube.com/watch?v=12kF9NDOBgU)

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Cookie and Dave Wiebe: We are fifty-somethings who've come back to Newton, KS from working at Woodstock School in India, due to Cookie's diagnosis in July of 2010, of advanced ovarian cancer. While not the adventure we anticipated at this stage of life, it is - never-the-less - a true adventure. We are grateful to all who are willing to walk this road with us. Twitter Updates follow me on Twitter
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