Tumor mutations, survival in stage 3 colon cancer differ by race

Genetic tumor mutations status in BRAF and KRAS genes and survival rates in stage 3 colon cancer patients differ based on race, according to an analysis of a phase 3 randomized trial cohort.

“These findings put the issue of race more prominently on the radar of investigators that cancer biology may contribute to race-based disparities,”Harry Yoon, MD, an oncologist at Mayo Clinic, said in a press release. “While it is too early to change the way we treat these patients, our results indicate that future studies are needed to examine potential biological drivers of these differences more closely.”

Yoon and colleagues conducted a detailed analysis of BRAF and KRASmutation status and mismatch repair (MMR) protein expression in the resected colon adenocarcinomas of 3,305 stage 3 colon cancer patients who were enrolled in a previous trial (Alliance N0147). The mutations were analyzed in relation to the patients’ races (white, n = 2,916; black, n = 240; Asian, n = 149). The 2,931 patients who received FOLFOX-based therapy were then analyzed for associations between race and disease-free survival (DFS) or time to recurrence (TTR).

“The role of the biology of colon tumors according to race has not been examined as extensively,” Yoon said in the press release. “This biology can be reflected in the genetic makeup of tumors, as well as by whether and how quickly cancer returns after the patient has been treated.”

They found that BRAF V600E mutations were twice as frequent in the tumors of whites (13.9%) compared to Asians (5.6%; P < .001) and blacks (6.4%; P = .009). KRAS mutations were found to occur most frequently in the tumors of blacks (44.1%) compared to Asians (27.8%; P = .001) and whites (34.9%; P = .07). KRAS/BRAF wild-type tumors were found to occur most frequently in the tumors of Asians (66.7%) compared to blacks (49.5%; P = .001) and whites (51.2%; P < .001; overall, P < .001).

The outcomes analysis revealed significant interactions between race and age (P = .01) and N stage (P = .005). Multivariate analysis adjusting for BRAF and KRAS mutations and other covariates showed that among patients younger than age 50 years , blacks had shorter DFS (HR = 2.84; 95% CI, 1.73-4.66) and TTR (HR = 2.71; 95% CI, 1.61-4.54) compared to whites. Among patients with N1 tumors, blacks also had shorter DFS (HR = 1.54; 95% CI, 1.07-2.29) and TTR (HR = 1.71; 95% CI, 1.13-2.58) compared to whites.

“Because all patients were treated and had their disease monitored in a clinical trial, suboptimal treatment, differences in cancer stage, or reduced access to care cannot adequately explain the disparity,” Yoon said in the press release.

“In addition to published data indicating that a limited number of genes are preferentially mutated in colon cancers from black vs. white patients, our study revealed differences in the mutation frequencies of BRAF and KRAS oncogenes that provide prognostic information in colon cancer patients,” Frank Sinicrope, MD, an oncologist at Mayo Clinic, said in the press release. “Our data provide further evidence that colon cancers from blacks are intrinsically different and are associated with more aggressive clinical behavior in young black patients.”

In a related editorial, Chyke A. Doubeni, MD, MPH, and Anil Rustgi, MD, both from University of Pennsylvania Perelman School of Medicine, wrote that this study is “an important contribution to understanding [colorectal cancer] disparities.” However, they added that “knowledge of the mechanisms for racial disparities in CRC remains incomplete, but the prescription is to eliminate variation in the quality of care received along the entire care continuum. This is even more important in the genomic era to assure that all patients realize the benefits of scientific advances.

“A multipronged approach involving research, policy, health care delivery transformation, and medical education is necessary to realize the ideal of eliminating health disparities, and CRC is an excellent model for this quest, particularly to identify biomarkers for the disproportionate high risk of tumor recurrence in younger blacks as documented by Yoon et al,” they concluded. – by Adam Leitenberger

Disclosures: The researchers, Doubeni and Rustgi report no relevant financial disclosures.