American Association for Cancer Research
Browse
10780432ccr113265-sup-ccr-11-3265fig1-3tab1-2.pdf (225.7 kB)

Supplementary Figures 1 - 3, Tables 1 - 3 from Molecular Epidemiology of EGFR and KRAS Mutations in 3,026 Lung Adenocarcinomas: Higher Susceptibility of Women to Smoking-Related KRAS-Mutant Cancers

Download (225.7 kB)
journal contribution
posted on 2023-03-31, 17:07 authored by Snjezana Dogan, Ronglai Shen, Daphne C. Ang, Melissa L. Johnson, Sandra P. D'Angelo, Paul K. Paik, Edyta B. Brzostowski, Gregory J. Riely, Mark G. Kris, Maureen F. Zakowski, Marc Ladanyi

PDF file - 225K, Supplementary Figure 1. (A) Gender differences in frequency of EGFR mutations by stage. Men with EGFR mutations presented at the late stage more often than women (118/170, 69% vs. 235/423, 56%; p=0.002); women predominated at stage I (31% vs. 19%, p=0.004). (B) Stage distribution of EGFR exon 19 del and EGFR L858R. EGFR L858R were significantly more frequent at stage I than exon 19 del (83/246, 34% vs. 82/347, 24%; p=0.009); Fisher exact test, P value <0.01 is considered significant. Supplementary Figure 2: (A) Age and (B) stage distribution of KRAS mutations (4 major subtypes) Supplementary Figure 3: EGFR mutation nomogram ROC curve in the validation cohort. Supplementary Table 1. (A) The association of the smoking-free years and pack-years of smoking with EGFR mutational status. Smoking-free years impact on likelihood of EGFR mutation. (Multivariate logistic regression analysis). (B) The association of the smoking-free years and pack-years of smoking with KRAS mutational status. Smoking-free years do not impact on likelihood of KRAS mutation. (Multivariate logistic regression analysis). Supplementary Table 2. Age and gender differences in pack-years of smoking in relation to KRAS mutation nucleotide change. Women with G>T transversions had smoked less (average 34 pack-years vs. 40 pack-years, p=0.001) and were younger than men with the same nucleotide change (median age 64 vs. 67, p=0.006). Fisher exact test, P value <0.01 is considered significant.

History

ARTICLE ABSTRACT

Purpose: The molecular epidemiology of most EGFR and KRAS mutations in lung cancer remains unclear.Experimental Design: We genotyped 3,026 lung adenocarcinomas for the major EGFR (exon 19 deletions and L858R) and KRAS (G12, G13) mutations and examined correlations with demographic, clinical, and smoking history data.Results:EGFR mutations were found in 43% of never smokers and in 11% of smokers. KRAS mutations occurred in 34% of smokers and in 6% of never smokers. In patients with smoking histories up to 10 pack-years, EGFR predominated over KRAS. Among former smokers with lung cancer, multivariate analysis showed that, independent of pack-years, increasing smoking-free years raise the likelihood of EGFR mutation. Never smokers were more likely than smokers to have KRAS G > A transition mutation (mostly G12D; 58% vs. 20%, P = 0.0001). KRAS G12C, the most common G > T transversion mutation in smokers, was more frequent in women (P = 0.007) and these women were younger than men with the same mutation (median 65 vs. 69, P = 0.0008) and had smoked less.Conclusions: The distinct types of KRAS mutations in smokers versus never smokers suggest that most KRAS-mutant lung cancers in never smokers are not due to second-hand smoke exposure. The higher frequency of KRAS G12C in women, their younger age, and lesser smoking history together support a heightened susceptibility to tobacco carcinogens. Clin Cancer Res; 18(22); 6169–77. ©2012 AACR.

Usage metrics

    Clinical Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC