Today I will be discussing a number of reasons why having a genetic mutation called Lynch Syndrome does not mean a definitive future diagnosis of cancer. First, I would suggest that you read my recent post on Epigenetics to get a better understanding of the relationship between our genes (DNA) and actual gene expression.
What is Lynch Syndrome
Lynch syndrome is characterized as a genetic predisposition to certain types of cancers, mainly colorectal and endometrial, and is estimated to be responsible for 1-3% of all colorectal and endometrial cancers in our population (1). Do not be alarmed by this, I will explain later in the post, but it is estimated that individuals with Lynch Syndrome have a 20-70% chance of colorectal cancer by the age of 70 (2); however, risk estimates are extremely variable and not precise (3)…more on this later.
With that in mind, Lynch Syndrome is the most prevalent human hereditary cancer syndrome (1) and there have been 3000 identified DNA mutations and variants associated with Lynch Syndrome (1). These 3000 DNA variants are all found in our Mismatch Repair (MMR) genes, and the most common variants in Lynch Syndrome are found in the MSH2 and MLH1 MMR DNA complexes. Sorry if that was a bit technical, they are just names.
How Does Lynch Syndrome Increase Cancer Risk?
Since Lynch Syndrome involves MMR genes we need to understand how MMR genes function. As you know, our DNA must be present in all of our cells; so, when a new cell is made (constantly happening in our body), DNA must be copied from an existing cell to the new cell. This is a complicated process and sometimes errors occur (mutations); therefore, the copied DNA must be “proofread” and destroyed or fixed if errors are found. This is where MMR genes come in. They are responsible for producing the proteins that read copied DNA and signal destruction of new cells with DNA errors (1). Additionally, MMR proteins play a role in identifying and signaling the destruction of existing cells that have experienced DNA damage (from toxin/oxidative stress exposure for instance) (1). Both of these actions are extremely important for cancer prevention for a number of reasons but mainly, DNA errors in cancer preventing genes (ex. tumor suppressor or proto-oncogenes) can lead to uncontrolled cell growth and ultimately cancer.
In a nutshell, DNA variants associated with Lynch Syndrome impair our ability to properly regulate DNA replication and/or destroy cells with damaged DNA; thereby increasing the likelihood of DNA irregularities in genes that help prevent/destroy cancer.
I have mentioned this before, but genetic risk does not mean definitive diagnosis. With regards to chronic health conditions, there are very few that are 100% linked to DNA alone. Most conditions do have a genetic link, but the penetrance (actually getting the condition) is so variable we know there are other factors involved such as our environment/lifestyle. This is no different for Lynch syndrome.
Depending on the source, the estimated risk of cancer for those with Lynch Syndrome is extremely variable from 2-70% depending on gender, age, and type of cancer. If cancer development from Lynch Syndrome was 100% genetic, we would see cancer occurring in all people with these genetic variants at or near 100% of the time. The most interesting study I have found for cancer risk percentages came from a 2014 study by Dowty et. al (3). The study was specific to MLH1 and MSH2 mutations and risk was identified by gender, age, and type of cancer in 2 ways. First was the cumulative risk of developing a cancer by a certain age (see first table), and second was the risk of developing a cancer in the next 10 years after being cancer free up to a certain age (see second table).
As you can see, the longer someone with Lynch Syndrome goes without getting cancer, the risk can actually decrease.
So, If you ask what your personal risk of developing cancer is if you have Lynch Syndrome; unfortunately, no one can give you an exact number, but it is safe to say you are at a higher risk than the general population….HOWEVER, given the variability in risk, we know there are ways to significantly reduce risk, just like there is with the non-Lynch Syndrome population. Lynch Syndrome does not mean you will get cancer! So, let’s see what some of the things you can do to reduce your risk as much as possible are.
Lifestyle Risk Factors
To understand how to reduce the risk of developing cancer with Lynch Syndrome, we need to identify what the non-genetic risk factors actually are.
I really hope that anyone reading this is not a smoker, I mean come on people it’s 2016! Another reason to cut the smoking is that current smokers with Lynch Syndrome have 6 times the risk of non-smokers with Lynch Syndrome (4)!
Western Diet Type
Not surprisingly, there is evidence of up to a 1.7 time increased cancer risk in those with Lynch Syndrome who eat little whole fruits and vegetables, lots of snack food, fast food, fried food, refined grains, processed meats, and sugary foods (candy and soda) (5). Not only that, increased whole fruit and fibre intake is associated with a risk reduction of up to 50% (6). I think we are starting to get the picture that a diet low in processed/toxic foods and high in nutrient dense whole foods reduces risk. So, not surprisingly, evidence from rats shows that a Western diet high in processed milk, industrial seeds oils, and low in vitamins, minerals and fibre increases the risk of cancer in mice with Lynch Syndrome (7).
Aside from obesity being a major risk factor for those with Lynch Syndrome, no other lifestyle factor has truly been investigated (8). However, given the large variability in cancer development in the Lynch Syndrome population it is more than reasonable to conclude that there are many lifestyle factors impacting risk, such as stress management and physical activity for example.
Aside from the above, there is not a huge amount of research specific to Lynch Syndrome and environmental risk factors, at least not compared to general population risk factors. That being said, there is no doubt that the same factors that reduce cancer risk in the general public will be the same for those with Lynch Syndrome. Actually, addressing these factors in those with Lynch Syndrome could arguably cause greater risk reduction than that of the general population. This is simply because individuals with Lynch Syndrome are more susceptible to a poor lifestyle since their bodies have less of an ability to deal with cancer promoting environmental conditions. In support of this idea, rats with Lynch Syndrome put on a Western type diet showed metabolic and intestinal disturbances that were not seen in non-Lynch syndrome rats on that same diet (7). As such, my next post will focus on diet and lifestyle factors important for general cancer prevention, and therefore, even more important for those with Lynch Syndrome.
The Barefoot Golfer