PGxCheck...What is our DNA saying?

 

 

 

We need to consider how genetic information

can help us with respect to healthcare. We are able to perform genetic testing more readily,

but how are we using the results? Join in the discussion!

Welcome

Personalized medicine and pharmacogenomics (the influence of genetics on drugs) is here. It is in its infancy and we all will watch it grow. From healthcare professionals to the general public, pharmacogenomics and the broader area of personalized medicine will present a learning curve.


This blog is made possible through an individual making their genetic information available. 

As we learn what this individual's genetics are telling us...and what it is not telling us, we will discuss it. I am sure there will be many questions. We will have individuals from pharmacy, genetics, ethics, law, and other disciplines adding their expertise and thoughts to the discussion. I sincerely hope you will contemplate the information, formulate your thoughts, and participate in the discussion!

Introductory Information and Disease Risk: Prostate Cancer!

I thought it best to have a baseline with the discussions starting with the disease risk information. 

 

The human genome is made up of a sequence of four chemicals, called nucleotide bases and include adenine (A), guanine (G), thymine (T), and Cytosine(C). This sequence is our DNA and it is found in every cell of the body, that has a nucleus (i.e., nucleated cells), on 23 chromosomes. We get a set of chromosomes from each parent, so there are 46 chromosomes in each cell. The sequence of DNA from each parent is about three (3) billion bases long...the four chemicals in a long sequence. Based on DNA we are about 99.9% the same. Differences between individuals can be described as genetic variation. In some cases the genetic variation can be a result of a change in the sequence by one nucleotide base replacing another, such as an A replacing a G. For instance:

 

A sequence that is the most “common” sequence may be TCC CAG CTG GAA TCC GGT GTC

 

The variation may be: TCC CAG CAG GAA TCC GGT GTC, where A (adenine) replaced T (thymine).

 

This is called a single nucleotide change or single nucleotide polymorphism (SNP, pronounced “snip”), since one chemical replaced another. This change may result in a difference from one individual to another. We will have some examples of this over the coming weeks.

 

 

Disease Risk: The information provides information about increased risk of disease, average risk of disease and decreased risk of disease. Let’s start with increased risk of disease. According to 23andMe, I have 1.5 x the average risk of getting prostate cancer.

 

How was this information provided to me? Through what is called the “odds calculator”, where 26.7 men with a genetic make-up like me, according to 23andMe will develop prostate cancer where as with average risk 17.8 men out of 100 will develop the disease. The 1.5 x risk value is simply 26.7 divided by 17.8. Note that this is relative risk! Not absolute risk! Increased risk does NOT mean I will get the disease.

 

So what is the genetic basis for this increased relative risk of getting prostate cancer? I received genetic information from my mother and father that shows, on a region on chromosome number 8 (something called band 24) from each parent, I have a certain sequence of those four chemicals mentioned above and at one specific point I have a certain chemical base (remember one from my mother and one from my father), here being G and T. We typically write this as GT and this is termed the “genotype”. People that have a T from their mother and a T from their father, with the genotype being TT have average risk for prostate cancer. However, one of my parents passed along a G, where the T would be. This is a SNP or “snip”, one chemical replacing another. It turns out that this SNP is related to an increase in the risk of prostate cancer.

 

How is this SNP related to increased risk of prostate cancer? This SNP (G for T on one of the number 8 chromosomes) was shown to be related to an increase risk of prostate cancer in a study of more than 2300 Caucasian males. This study is called a “Genome Wide Association Study” (GWAS...we have abbreviations for everything!)

 

It turns out from other studies that there are other SNPs (single base difference at other places on DNA) that have been related to increased risk for prostate cancer in middle-to-late age Caucasian males. In a study of over 3600 male Caucasians, the SNP mentioned above, along with four other SNPs (snips) and family history was related to the increased risk. So, we can say that the group of five SNPs and the family history provides the cumulative (here for discussion) risk.

 

Here are my genotypes for the five potential SNPs (in general terms here) making up the cumulative risk relative to the normal risk genotype:

SNP 1 (from above) – Normal risk genotype TT, my genotype GT – increased risk

SNP 2 – Normal risk genotype CC, my genotype CC – normal risk

SNP 3 – Normal risk genotypes AG or GG, my genotype AA – increased risk

SNP 4 – Normal risk genotype GT, my genotype GT – normal risk

SNP 5 – Normal risk genotype CC, my genotype CC – normal risk

Family history – unknown (I am adopted). *Update - I know some family history, but not related to prostate cancer.

 

So, out of the five SNPs that make up the cumulative risk, I have two SNPs that are related to increased risk.

 

What does this mean to me. I will talk to my doctor about this and I will look into “prostate health”. What if I did not know this information? I would follow the American Cancer Association recommendations and talked to my physician. Am I going to get prostate cancer? I do not know, but I will be diligent in my healthcare.


I hope that the presentation of the information makes sense. I went to a great deal of work to go to this level of understanding my relative risk as presented in my data. Most individuals will look at the summary data and not look at this technical level. Again risk does not mean it will happen. The genetic-based risk must be looked at in the context of overall risk that includes diet, and the environment among other potential risk factors.

 

What are your thoughts?

26 comments | Add a New Comment
1. Myranda S | September 06, 2013 at 04:26 PM EDT

So in turn yourself having 2 out of the 5 potential SNP's increased your risk, would having all 5 conclude that you would definitely have prostate cancer or some predisposition for it, or could the data just be a \maybe\?

2. DFK | September 06, 2013 at 10:31 PM EDT

Even if all 5 were increased risk SNPs, it would still be relative risk and would not mean I will get the disease for sure. In reality, you need to combine the genetic-based risk with environmental and lifestyle factors when considering risk. Great question!

3. Katlyn Brown | September 07, 2013 at 10:59 AM EDT

So as I understand,if you have any of the potential SNP's it just means you have an increased risk. Are there any combinations or ones that mean you will get the disease or is it just an increased risk ?

4. Victoria D | September 07, 2013 at 03:32 PM EDT

Are there certain properties of the nucleotide bases that cause them to result in you having that increased risk?

5. Allie H | September 07, 2013 at 05:03 PM EDT

Being that I am a P1, I have really haven't had that much background in genomes and genetics (sophomore high school biology to be exact). From my understanding, SNP's put someone at an automatic increased risk, right?

6. Kara Horvath | September 07, 2013 at 09:02 PM EDT

Besides the lifestyle factors that are taken into account, could a medication potentially reduce the relative risk of prostate cancer? Or even in any situation where a risk of a certain disease is there?

7. Jasmine H | September 08, 2013 at 08:51 PM EDT

So do they consider a SNP just every 2 pairs in the sequence in question? For example: the sequence is CTG CAG ATA would the SNPs then be CT GC AG AT...

8. DFK | September 09, 2013 at 09:04 AM EDT

Katlyn: So as I understand,if you have any of the potential SNP's it just means you have an increased risk. Are there any combinations or ones that mean you will get the disease or is it just an increased risk ? Response: The SNPs are related to risk and again, relative risk. There is no know SNP that results in absolute risk.

9. DFK | September 09, 2013 at 09:14 AM EDT

Victoria:Are there certain properties of the nucleotide bases that cause them to result in you having that increased risk? Response: The progression from a given SNP, a change in one nucleotide at a given position can result in a codon (three nucleotides in sequence) that results in a different amino acid in the protein. i.e., Codons result in the production of amino acids and amino acids form proteins. With a SNP, and a different codon, a different protein can result which may result in abnormal cellular function. As an example, CAG makes the amino acid glycine, and with a SNP where T replaces A, CTG makes the amino acid leucine. This could then change how the protein that contains leucine works. This could be a protein that may be malfunctioning and results in increased cancer risk.

10. DFK | September 09, 2013 at 09:20 AM EDT

Allie: Being that I am a P1, I have really haven't had that much background in genomes and genetics (sophomore high school biology to be exact). From my understanding, SNP's put someone at an automatic increased risk, right? Response: Actually, SNPs can increase the risk, have no effect on risk, or even decrease risk, but it does not mean an individual will 'automatically' get a disease or conversely, not get a disease. This is because there are other factors, e.g., environmental. For instance I have a decreased risk of coronary heart disease. This does not mean I can sit around and eat cheeseburgers all day long and be free of potential heart disease.

11. DFK | September 09, 2013 at 09:28 AM EDT

Kara: Besides the lifestyle factors that are taken into account, could a medication potentially reduce the relative risk of prostate cancer? Or even in any situation where a risk of a certain disease is there? Response: This is an important point you raise. Right now, it costs a couple of thousand dollars to have your entire genome sequenced. This, at some point I believe, will be a standard, where everyone has their genome sequenced. The data will be stored on a secure system and when certain genetic information is needed, the data will be queried. This is called preemptive genetic testing. That is, the data is there before it is needed. The point you raise is part of preventive medicine. If an individual has a certain risk, they can take steps to prevent the consequences of that risk. For instance, some individuals have a severe form of high cholesterol (familial hypercholesterolemia - genetic based). These individuals will take a statin to help prevent the heart disease that can result. We are changing from reactive medicine to preemptive medicine.

12. DFK | September 09, 2013 at 09:35 AM EDT

Jasmine: So do they consider a SNP just every 2 pairs in the sequence in question? For example: the sequence is CTG CAG ATA would the SNPs then be CT GC AG AT... Response: A SNP is where one nucleotide base is replaced by another. The key is how this alters a codon, see my response to Victoria above. The three nucleotide bases in sequence codes for a specific amino acid to form a protein. There are other DNA changes that can happen too, and we may describe more of these later.

13. Whitney R | September 09, 2013 at 01:00 PM EDT

Other than lifestyle factors and taking medication, is there any other way to reduce the relative risk of prostate cancer?

14. Brady | September 09, 2013 at 07:10 PM EDT

I personally think that knowing what your DNA says you're at an increased risk for is beneficial because then you can find out how to keep up with your health and make preparations in case the worst comes to pass.

15. Meagan B | September 09, 2013 at 08:18 PM EDT

I think it is crazy how one simple change could make you at risk for a serious disease. It would be interesting to find out what a couple things change and how severe the risk could be/how many different diseases one could be at risk for a one time. As we go through this human genome evaluation, I think it will be interesting to figure out what you can all discover just from a simple saliva sample.

16. DFK | September 10, 2013 at 09:30 AM EDT

Whitney: Other than lifestyle factors and taking medication, is there any other way to reduce the relative risk of prostate cancer? Response: I think you have actually stated the approaches to decreasing risk. Certainly, in general, exercise is a positive too.

17. Seth Wollenhaupt | September 10, 2013 at 10:13 AM EDT

I believe it will be interesting discovering how these mutations occur and what we,as humans, can do to help these mutations. Having a couple uncles die of cancer, it is really interesting to understand what happened with their genes and what we may be able to do to prevent this in the future.

18. Mikayla S | September 10, 2013 at 02:05 PM EDT

So I understand that it is possible to have an increased risk of prostate cancer due to these SNP's, but is it more, less, or just as common to have SNP's that decrease one's risk for prostate cancer?

19. DFK | September 10, 2013 at 03:34 PM EDT

Mikayla: So I understand that it is possible to have an increased risk of prostate cancer due to these SNP's, but is it more, less, or just as common to have SNP's that decrease one's risk for prostate cancer? Response:Most individuals have DNA that imparts \typical\ relative risk. Some will have DNA that imparts decreased relative risk. Your comment about \just as common\ can be looked at this way - Not all three, i.e., increased, typical, or decreased relative risk are seen at the same frequency in the population. Actually, typical relative risk is most common. We will discuss the frequency of DNA variants a bit later.

20. Kassie G | September 11, 2013 at 01:08 PM EDT

I think it is beneficial to know if you have an increased risk to possibly develop a disease because you can then get regular check ups with doctors and if you actually get the disease then your doctors can make an early diagnosis.

21. Paige Ordean | September 11, 2013 at 05:32 PM EDT

It would be nice to know if I had an increased risk for a disease because then I would be able to avoid some of the things that could possibly cause the disease/ make it worse. It would also be interesting to learn what causes diseases and thus being able to possibly find a cure.

22. DFK | September 11, 2013 at 06:02 PM EDT

Kassie and Paige: Two great points. If you have increased risk due to genetics, then you can try to affect the other risk factors. You can't change your DNA, but you can do your best to minimize other risks. See the physician and follow good health habits.

23. Alexandria L | September 13, 2013 at 01:16 PM EDT

I understand your points about being able to prepare for the disease or take measures to minimize the risks of getting the disease. I think if I had one of these tests done, though, and it showed I was at risk of something, I would just stress out and worry about when it would strike. I'd rather live in ignorance and enjoy my life, and then learn how to live with the disease if I contracted it later.

24. DFK | September 14, 2013 at 11:48 AM EDT

Alexandria: I understand your points about being able to prepare for the disease or take measures to minimize the risks of getting the disease. I think if I had one of these tests done, though, and it showed I was at risk of something, I would just stress out and worry about when it would strike. I'd rather live in ignorance and enjoy my life, and then learn how to live with the disease if I contracted it later. Response: Good point. This is how some people will respond! Just wait until we get to one more disease risk...that begins with an \A\. More to follow!

25. Joshua Macks | September 15, 2013 at 10:22 PM EDT

I believe that it is a great thing that we can find out if we are at increased risk for a potential disease, so that we might take measures now in order to fight that disease. One question though, is it possible to have a SNP that would guarantee you would, or would not, get a certain disease, such as Alzheimer's or Parkinson's? The reason I ask is I have relatives on both sides of my family who have both of those diseases.

26. Kole Wallace | February 11, 2014 at 01:21 PM EST

Wow, I think its amazing how just .01% of a genome creates a completely different individual. People are so diverse and have so many varying traits and its just crazy to think how similar we all are from a genetic standpoint. Also, its crazy to think that a single nucleotide can put you at risk for a disease, of course its even crazier to think that we can identify that nucleotide and figure out what it can do if its different.

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