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?