Risk Scores

I thought it would be helpful to share how I think about and approach aspects of my own health, so today I am going to share a polygenic risk report I recently had done on myself.

To start with, what is a polygenic risk report? It is a document that reports your polygenic risk scores on multiple diseases, giving a percentile calculated from a person's genetic data for each disease that represents the sum of the number of risk alleles associated with the disease of interest weight by the corresponding effect size of those alleles on the disease compared to the risk in the general population.

That is a mouth full, so for me it becomes much more intuitive when you look at one of these polygenic risk scores in graph form:

Here we have my own personal polygenic risk score for Alzheimers and Dementia. As you can see it is nice and 'relatively' low so I am not working against a stacked deck. Wooohooo!

But there was a risk score that returned a value that has made me take take action. See for yourself:

Ut oh...

First of all, let's keep things in perspective. If you are going to be at elevated risk for any cancer, prostate cancer is not the worst one to have. Most men die "with" prostate cancer as opposed to "from" prostate cancer. There are screening tests including PSA, DREs, and MRIs. There are multiple treatment options including radiation and surgery, and most importantly there are many modifiable risk factors I can act on NOW to decrease and potentially eliminate the initiation and progression of prostate cancer in my future.

Now let's get a little into my thinking on how I approach this. For me personally, my elevated prostate cancer risk is the number one entity preventing me from one of my centenarian decathlon goals of being able to initiate and maintain an erection in my 11th decade of life. We covered the ideas of the 'centenarian decathlon' pioneered by Dr. Peter Attia and the idea of the 'penis being a barometer of your overall health' in prior posts, but as is probably clear, it is important to me as a metric of my physical and emotional health to make sure I have the optionality for erections when I am old.

So what am I doing about this?

I have focused on identifying and reducing or eliminating any modifiable lifestyle factors that might increase my risk AND I am actively identifying and promoting the factors that make my body inhospitable to cancer.

Interesting... Say more.

For me personally, having both prongs of attack, the first aspect focusing eliminating the bad and the second aspect focuses on actively intimating the good, is an important paradigm. It makes me feel like I am not just restricting things in my life, I am actively bringing things into my life. It also makes me feel like I am covering all of my bases.

So let's get into more specifics examples of what this looks like translated into real life action.

• I eat a whole food, plant predominant diet.

  • There exists data on animal meat, eggs, and dairy intake being associated with increasing risks of death from prostate cancer as well as increased vegetable intake being associated with decreased risks of prostate cancer.

  • If you are interested, s resource worth looking into is Michael Gregor's website NutritionFacts.org

• I exercise, both zone 2 but more importantly some high intensity exercise

  • In the spirit of making my body inhospitable to cancer, I also specifically want to make it inhospitable to cancer metastasis. This is where rogue cancer cells split off from the original tumor and travel through the blood or lymph to distant sites, re-seed themselves, and start growing. This is when most cancers turn deadly. There was an interesting paper recently that showed people who did high intensity exercise has significant reductions in metastatic cancer. The thought process is that the elevated exercise consumes most of the glucose in the blood, leaving a lack of resources for any metastatic buds. Others have proposed interesting mechanisms focusing on the fact that cancer cells tend to be poorly made and fragile. The ideas is that the high intensity exercise transiently elevates the blood pressure and increases blood flow causing sheering forces that destroy would 'would be metastatic cancer cells' in the blood before they can seed other tissues.

• Sleep is a non negotiable for me

  • I get at minimum 7 hours of sleep and always aim for the Sisyphean goal of 8 and 1/2 hours in bed.

• I don't smoke

• I now rarely drink, and only when the social gains outweigh the marked health consequences.

• I check my PSA.

  • PSA stands for Prostate Specific Antigen. It is a glycoprotein (protein with a sugar on it) that is made in the prostate that naturally leaks out into the blood where you find it on your blood test.

  • Elevated levels of PSA can mean a lot of things, including prostate cancer but also enlargement of the prostate (BPH), inflammation of the prostate (prostatits), and recent manipulation of the prostate (recent ejaculation, vigorous bike riding) among others. It has become a relatively controversial screening test because of it's lack of specificity for prostate cancer causing increased treatments and anxiety in men who don't actually need intervention.

  • I am 37 at the time of writing this. The USPSTF (a body that gives recommendations on screening test) doesn't recommend considering PSA until the age of 55 and even then says that the decision should be an individual one after discussing the harms and benefits of screening with their doctor. The American Urological Association states that "Clinicians should offer prostate cancer screening beginning at age 40 to 45 years for people at increased risk of developing prostate cancer based on the following factors: Black ancestry, germline mutations, strong family history of prostate cancer."

  • I am aware of the risks of over-diagnosis and over-treatment and am aware of my own family history and genetic risk and thus have chosen to go forward with continuing to get my PSA checked. I also know that I am very ok living in the grey. I have enough medical literacy to sleep well at night knowing that in the future I might have a hight PSA with an inconclusive work up and will have to make difficult decisions on incomplete information. I would rather have the data.

USPSTF recommendations for PSA screening:

USPSTF infographic on prostate cancer screening:

American Urological Assocaition PSA Screening Guideline Statments:

And at the end of the day I keep things in perspective especially when it comes to polygenic risk scores. This risk score is a data point to be considered in the larger scheme of thousands of other data points. To echo the mantra of many other practitioners, 'your DNA is not your destiny'.

It varies depending on who you ask, but most individuals will quote you an 80%/20% or a 90%/10% rule when it comes to lifestyle vs genetic determinants with health. That means that while you might have genes that can predispose you to a specific disease, 80 to 90 percent of the outcomes you will experience are driven by lifestyle.

This is incredibly empowering!

You have some meaningful control of your health.

To me, this helps me to really frame all the data that comes in, keeping it in proportion to it's value, and tying it into the larger narrative of my health. It allows me to major in the majors as opposed to becoming myopic and majoring in the minors.

Wei JT, Barocas D, Carlsson S, et al. Early detection of prostate cancer: AUA/SUO guideline part I: prostate cancer screening. J Urol. 2023;210(1):45-53.

Wei JT, Barocas D, Carlsson S, et al. Early detection of prostate cancer: AUA/SUO guideline part II: considerations for a prostate biopsy. J Urol. 2023;210(1):54-63.