Frequency of EGFR and KRAS mutations in patients with non small cell lung cancer by racial background: do disparities exist?

Abstract

Introduction: Mutations in EGFR and KRAS can impact treatment decisions for patients with NSCLC. The incidence of these mutations varies, and it is unclear whether there is a decreased frequency among African Americans (AfAs).

Methods: We performed a retrospective chart review of 513 NSCLC patients undergoing EGFR and KRAS mutational analysis at the Hospital of the University of Pennsylvania between May 2008 and November 2011. Clinical and pathologic data were abstracted from the patients' electronic medical record.

Results: Of 497 patients with informative EGFR mutation analyses, the frequency of EGFR mutation was 13.9%. The frequency of EGFR mutations was associated with race (p < 0.001) and was lower in AfA patients compared to Caucasian (C) patients but did not reach statistical significance (4.8% vs. 13.7%, p = 0.06). Mean Charlson Comorbidity Index and number of cigarette pack years were significantly lower in patients with EGFR mutations (p = 0.01 and p < 0.001, respectively). Multivariable logistic regression analysis showed a significant association between race and EGFR mutation (p = 0.01), even after adjusting for smoking status (p < 0.001) and gender (p = 0.03). KRAS mutation (study frequency 28.1%) was not associated with race (p = 0.08; p=0.51 for Afa vs. C patients), but was more common among smokers (p < 0.001) and females (p = 0.01).

Conclusions: Based on multivariable analysis, even after adjusting for smoking status and gender, we found that race was statistically significantly associated with EGFR mutation, but not KRAS mutational status. To the best of our knowledge, this is the largest single institution series to date evaluating racial differences in EGFR and KRAS mutational status among patients with NSCLC.

Keywords: EGFR; KRAS; NSCLC; Racial disparity.

Figure 1

Consort Diagram. *When the tumors had different histologies, they were regarded as separate primary cancers and both records were included. When two records of the same primary tumor were noted, the tumor testing with the most complete information was included. This usually occurred as a result of a previously indeterminate or inconclusive test result.

Figure 2

Association of Gender, Race and EGFR or KRAS positivity by Smoking Status. Females are represented by blue bars and males are represented by green bars. 2A. Caucasian female non-smokers had higher rate of EGFR positivity compared to African American female non-smokers, which did not meet statistical significance (44.4% (20/45) vs. 22.2% (2/9), p=0.28). Caucasian male non-smokers had a higher rate of EGFR positivity compared to African American male non-smokers; this difference did not meet statistical significance due to small number of African American never-smokers (39.1% (9/23) vs. 0% (0/1), p=1.00). 2B. Caucasian female smokers had a significantly higher rate of EGFR positivity than African American female smokers (11% (20/182) vs. 0% (0/31), p=0.05). Caucasian male smokers had a similar rate of EGFR positivity as African American male smokers (3% (4/135) vs. 4.5% (1/22), p=0.54). 2C. Caucasian female never-smokers had higher rate of KRAS mutant positivity compared to African American female never-smokers; this difference did not meet statistical significance (7.1% (2/28) vs. 0% (0/8), p=1.0). Caucasian male non-smokers had a higher rate of KRAS mutant positivity compared to African American male never-smokers, which did not meet statistical significance due to small number of African American never-smokers (18.8% (3/16) vs. 0% (0/1), p=1.00). 2D. Caucasian female smokers had a similar rate of KRAS mutant positivity as African American female smokers (42.5% (57/134) vs. 41.7% (10/24), p=1.0). Caucasian male smokers had a similar rate of KRAS mutant positivity as African American male smokers (22.8% (23/101) vs. 15.8% (3/19), p=0.76).