Histological subtype and smoking status, but not gender, are associated with mutations in non-small-cell lung cancer.

Mutations in () commonly occur in non-small-cell lung cancer (NSCLC) patients characterized by female gender, never-smoker status and adenocarcinoma histology. The aim of this study was to determine whether gender is a confounding factor for mutations in NSCLC. To elucidate the confounding effect, Pearson's χ test and logistic regression models were used to correlate these characteristics with mutations in 426 NSCLC patients treated at our institutes. Of those 426 NSCLC patients, 47% were females, 57% were non-smokers and 84% had adenocarcinomas. The multivariate logistic regression analysis demonstrated that never-smoker status [odds ratio (OR)=3.49, 95% confidence interval (CI): 1.99-6.13; P<0.001)] and adenocarcinoma (OR=9.43, 95% CI 3.62-24.56; P<0.001) were associated with mutations; however, gender was not (OR=1.25, 95% CI: 0.73-2.15; P=0.416). Furthermore, gender was not associated with mutation subtypes (OR=1.19, 95% CI: 0.56-2.50; P=0.650). The frequency of mutations among females and males was not different in non-smokers (64.8 vs. 55.8%, P=0.204) or ever-smokers (27.8 vs. 24.2%, P=0.775). Therefore, if the assessment for mutation status was limited to non-smoking females with adenocarcinoma, up to 40% of the patients harboring mutations would be precluded from the benefit of inhibitor therapy. Our results indicated that gender is a confounding factor for mutations in NSCLC and suggested that gender may not be associated with tumorigenesis in NSCLC-harboring mutations.