Younger CRC Patients Often Have Hereditary Syndromes

July 24, 2015

Patients diagnosed with colorectal cancer at younger ages are more likely to have an underlying hereditary syndrome than older patients, according to a new study.

Patients diagnosed with colorectal cancer (CRC) at younger ages are more likely to have an underlying hereditary syndrome than older patients, according to a new study. The finding suggests genetic testing and counseling are warranted for younger CRC patients.

CRC is generally considered a disease of older individuals, with most diagnoses made between the ages of 65 and 74 years. Younger diagnoses have increased in recent years, though, as has research interest in these younger patients. Still, most studies of younger CRC patients have focused on those diagnosed at younger than 40 or 50 years, and the degree of influence of family history and hereditary syndromes is not yet well understood.

In a study led by Eduardo Vilar, MD, PhD, of MD Anderson Cancer Center in Houston, researchers analyzed details of 193 patients diagnosed with CRC at age 35 or younger. Results were published online ahead of print in the Journal of Clinical Oncology.

Most of the patients were female (52.3%) and white (75.1%), and most presented with either stage III (30.1%) or stage IV (46.6%) disease. Twenty-three patients (11.9%) had a first-degree relative with CRC, and 25.9% had a first-degree relative with any other cancer. For second-degree relatives, these rates were 32.1% and 67.4%, respectively.

In all, 34.7% of the study population had a hereditary cancer syndrome based on a positive genetic test result, polyposis phenotype, or a tumor that displayed mismatch repair gene deficiency. Twenty patients had a polyposis phenotype, and 13 had classic FAP with a pathogenic APC mutation.

Those without an identifiable phenotype underwent evaluation for Lynch syndrome, and 23 (34.3% of those with hereditary syndromes) tested positive. Another 22 patients (32.8%) had mismatched repair deficient tumors but did not harbor pathogenic mutations, and were thus diagnosed with mutation-negative Lynch syndrome.

Most, though not all, patients with hereditary syndromes had some family history consistent with the diagnosis. In all, non-hereditary CRC cases were more likely to present with metastatic disease (P < .001) and to have other markers of aggressive tumor behavior. Patients with hereditary syndromes were more likely-as expected-to have a first-degree relative with CRC (P < .001), as well as to have a personal history of another cancer (P < .001).

“Our results support a referral to genetic counseling for hereditary cancer syndromes for all patients diagnosed with CRC at 35 years or younger, regardless of family history of CRC,” the authors concluded. “Adolescent and young adult patients with CRC should be referred for a hereditary cancer work-up and may benefit from the use of comprehensive hereditary CRC genetic testing panels.”