Molecular Testing for Colorectal Cancer: 5 Pressing Questions Answered

There are several risk factors that can contribute to a diagnosis of colorectal cancer. Inherited factors play a large role in that risk. About 5 to 10 percent of people who develop the disease have inherited gene mutations. Determining these mutations can not only help an individual understand their risk, but also other members of their family — potentially even preventing it.

Which patients with colorectal cancer should receive molecular testing, and at what point?

In an interview with CURE, Matthew Yurgelun, M.D., assistant professor of medicine at Harvard Medical School and gastrointestinal medical oncologist at Dana-Farber Cancer Institute, explained who should receive molecular testing, what kinds of questions patients should be asking their medical team and what to do if a patient doesn’t know their personal family history.We have historically recommended germline testing for any patient with colorectal cancer who has a particularly strong family history of colon cancer and any patient with colon cancer with a strong family history of endometrial, ovarian and other cancers linked to Lynch syndrome, also, for any patient with colorectal cancer who has a significant number of adenomas or polyps.

If you look beyond Lynch syndrome, which has historically been known as the most common inherited colorectal cancer syndrome, you end up finding a lot of inherited mutations and there doesn’t seem to be, at least from our data, specific factors that tell us which individuals need germline testing.

It raises the question of should we be performing testing on all individuals with colorectal cancer, which is a pretty slippery slope. I think the counterargument to that is that some of these inherited mutations still have a lot of questions behind them even when we find these mutations and so we’re not quite ready to be recommending germline testing for all individuals with colorectal cancer. I think we would come up with as many questions as we do answers if we were to do that.

At the very least, my current recommendation to my patients is to undergo germline testing if there is any evidence of mismatch repair deficiency in the tumor to suggest Lynch syndrome, any evidence of inherited polyposis and if they’re diagnosed with their colorectal cancer before the age of 50, but for individuals who have less striking family histories of other cancers.

What kinds of questions should patients be asking their health care team?

I think it becomes a situation where we should be thinking about germline testing more broadly and have a much more liberal threshold for such testing than we traditionally do.It’s important for patients who have had prior genetic testing to readdress that with their health care team. Patients with a prior history of colorectal cancer who maybe underwent germline testing in the past and were found to have no abnormalities may want to reconsider testing now that there are tests available that can test a little bit more broadly, especially if they had particularly concerning personal or family histories of cancer. The testing has become more sophisticated over the past several years.

For patients who are newly diagnosed and have never had testing, I think it’s important that these patients bring up the notion of familial risk. Many patients with cancer, especially those with more advanced disease, have a lot on their plate and their health care providers are probably often distracted about making sure they are getting the right chemotherapy, as well as the right social and symptomatic supports, so unfortunately genetics often falls a little bit down the priority, in some cases.

What do you suggest patients who may not know their family health history do in such a case?

There are no approved therapies for colorectal cancer that target the cancer susceptibility genes. What is in the works here?

I certainly encourage patients to advocate for themselves about any concerns that they might have about inherited risks, especially as it applies to family members because testing is quite widely available at this point and it is something that many patients should be considering.There still can be reasons to consider germline testing. If patients have certain features in their tumors such as mismatch repair deficiency or microsatellite instability that absolutely would be a reason to consider germline testing. If they, themselves, have a history of other cancers or significant history of colorectal polyps, they should be considering testing regardless of whether they know their family history. And then, certainly patients with colorectal cancer who are diagnosed at a young age should consider germline testing. Family history is a big piece of how we access risk, but it’s not the only piece.As far as interventions that we consider for individuals found to have certain types of inherited susceptibility, screening is an incredibly powerful tool. In the setting of Lynch syndrome for example, individuals are typically recommended to undergo colonoscopies every one to two years. I often recommend every year usually beginning in their early 20s if they have a diagnosis of Lynch syndrome. The reason for such an aggressive recommendation is because we know it works. We know that colonoscopies are an incredibly powerful tool not just at early detection, but in colorectal cancer prevention.

We have really seen a sharp rise in young adults with colon cancer. Do you have any thoughts on what may be contributing to this?

Certainly, we have seen an increase in incidence of young adults with colorectal cancer, particularly rectal cancer and individuals in their 40s and their late 30s.

It doesn’t seem that genetics is a driving force behind that increasing incidence. We would assume that genetic factors should be remaining generally stable throughout the generations.

So, I think the assumption has been that it is lifestyle factors, environmental factors or interplays between the two, and maybe interplays with some subtle genetic factors that we haven’t come to understand just yet. But as far as some of the well understood genetic factors like Lynch syndrome and polyposis those are probably not playing any more of a role now than they did in the past because those factors should be remaining relatively stable over the generations.