Common Mutations May Lead to Worse CRC Outcomes in African-Americans

A set of genes that are more likely to be mutated in African-Americans vs Caucasians with colorectal cancer (CRC) appears to increase the risk of metastases and relapse in mutant compared with nonmutant versions, according to a new study published in the Journal of the National Cancer Institute.

African-American patients have worse stage-specific survival than other ethnicities, and mortality rates for CRC have risen over the past several decades in this group while they have declined in others. “The contributions of biological differences vs socioeconomic disparities to these striking disparities are largely unknown,” wrote study authors led by Joseph Willis, MD, of Case Western Reserve University and Case Medical Center in Cleveland.

In previous work, a set of 15 genes was shown to be 3.3 times more frequently mutated in African-American vs Caucasian patients with CRC. The new study analyzed how those mutations affect outcomes in a cohort of 66 patients with stage I to III CRC (27 were mutation-positive and 39 were mutation-negative).

Over a median follow-up period of 57 months, the mutation-positive patients had a higher relapse rate than mutation-negative patients, with a hazard ratio (HR) of 3.92 (95% CI, 1.18–13.09; P = .03). Eight of the 27 mutated cases relapsed, compared with only 4 of 39 nonmutated cases. The time to recurrence was significantly longer in nonmutated patients (P = .02).

The effect was stronger specifically in patients with stage III disease. Among those 33 patients, the HR for relapse when the mutations were present was 4.53 (95% CI, 1.16–17.72; P = .03), and the median disease-free survival was significantly shorter. In total, 7 of 15 mutation-positive stage III patients relapsed, compared with only 3 of 18 mutation-negative patients.

The authors noted that the study’s primary limitation is its restriction to a single tertiary care center. It is possible, though perhaps unlikely, that a confounding environmental or epidemiologic factor specific to that community could have influenced the results.

Still, they concluded that this set of commonly mutated genes “may define a high-risk subset of colon cancers that contributes to the overall observed disparity in colon cancer outcomes seen in African-Americans.” Further studies on these genes and their influence are warranted.