Germline genetic testing — where clinicians test for inherited mutations — is essential for patients with colon cancer, as the results may not only help guide their treatment options but can also let them know if they or their family members are at an increased risk for other cancers.

However, current recommendations call for screening of patients and then deciding if they are appropriate candidates for germline testing, which could lead to some patients with genetic mutations or inherited cancer syndromes falling through the cracks and not being identified, according to Rachel Pearlman, a genetic counselor at The Ohio State University College of Medicine.

In a recent interview with CURE®’s sister publication, CancerNetwork®, Pearlman discussed her research in genetic testing in patients with colon cancer, and why germline testing for all should be the way of the future.

Question: Can you explain your research regarding colon cancer genetic testing, and how it can help both patients and their family members?

Pearlman: The Ohio Colon Cancer Prevention Initiative, which we affectionately referred to it as the OCCPI study was exactly what the name implies. It was a statewide initiative in Ohio that was created to prevent colon cancer.

We know that individuals who are born with a germline pathogenic variant in a cancer predisposition gene have increased risk to develop specific types of cancer. Obviously the types of cancer depend on which gene isn't working correctly. By identifying individuals with colon cancer who have these germline pathogenic variants, we could then hopefully prevent them from getting different cancers in the future, and we could help their family members reduce their risk for cancers too.

The OCCPI study is the largest study to date that performed universal tumor screening … on everyone in the study. And we also did germline genetic testing with multi-gene, pan-cancer panels for those who met our germline testing criteria. And then we also did tumor sequencing for those with unexplained mismatch repair deficiency.

We also provided genetic counseling locally for those who tested positive for a germline pathogenic variant and no cost cascade testing and genetic counseling for the relatives of those found to have Lynch syndrome.

What were some of the highlights that came out of that research?

Importantly, we found that one in 14 (or 7%) of individuals with colon cancer will have at least one gene mutation increasing cancer risk. And we know that this is actually an underestimate of the true prevalence, because only our high-risk patients receive germline testing. In our study, the true prevalence is probably closer to 10 to 15%, as shown by some other studies.

We also found that one in 25, (or a little bit over 4%) of patients with colon cancer actually have Lynch syndrome, which is a higher frequency than what we had previously reported, which is likely due to improved technology with both the universal tumor screening and germline testing and it truly being universal being done on all-comers rather than targeted (and) based on your diagnosis or family history.

Also importantly, we found that 3% had a pathogenic variant and a non-Lynch syndrome gene, the most commonly being in ATM, which is thought it was a breast and pancreas gene (mutation). (We also saw mutations in the CHEK2 gene) which is thought of as a breast and colon (cancer) gene. APC, which is known to cause polyposis. Interestingly, (there were) BRCA 1 and 2 (mutations), which increases risk for breast and ovarian cancer.

So we were finding gene mutations … that we weren't necessarily expecting based on their colon cancer diagnosis. And for some of them, we weren't expecting them based on the family history either.

We also have some really interesting data in our young-onset cohort. We found that 16% of individuals diagnosed with colon cancer under the age of 50 had at least one gene mutation. We had published that a few years earlier. About 8% of those individuals have Lynch syndrome and 8% had no different hereditary syndrome.

The most import (finding), to come out of this research was that if universal tumor screening, which is recommended for every person who's diagnosed with colon cancer, had been the only method used to screen for hereditary cancer syndrome, then almost 40%, so 38.6%, of our patients identified to have a mutation would have been missed. (That’s) including 6.3% of those who are identified to have Lynch syndrome. We found that we're missing Lynch syndrome and mismatch repair proficient patients, and we found unexpected mutations in both the proficient and efficient mismatch repair patients.

What is on the horizon for genetic testing in colon cancer?

Hopefully genetic testing or germline genetic testing will be recommended for all individuals with colon cancer, which is a pretty big shift from our current guidelines, which are really based mostly on mismatch repair deficiency status, or age at diagnosis or family history criterion. There's a lot of burden on the practitioner trying to figure out who is the appropriate person to offer genetic testing to.

Once germline genetic testing is recommended for all colon cancer patients, or if that were to happen, that would certainly eliminate a lot of the burden on trying to figure out who is the right person to test. We know that everybody who has colon cancer is appropriate for testing.

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