Abstract B07: Meta-analysis of EGFR and smoking in lung cancer for population health in the global context
Authors: Kusuma Joyce D. , Shiao S. Pamela K. , Chen Hsiao-Ling 
Published: October 2015

Abstract
Purpose: The purpose of this meta-analysis is to examine the association between epidermal growth factor receptors (EGFR) and tobacco-smoking in lung cancer (LC) for population health in the global context. LC is the leading cause of cancer-related mortality in the United States at greater than three quarters of death as of 2010. Smoking is one of the well-known contributors to LC. However, there are LC cases who never smoke, typically who may have EGFR gene mutations. Current state of science on EGFR mutations showed inconsistent inclusion of smoking history. Some studies that included smoking history showed the associations of non-smoking status with EGFR mutations (exon 18-21) and smoking status with KRAS mutations (codons 12-13), they are mutually exclusive associations.
Procedure: Literature were searched through Cochrane, Excerpta Medica (Embase), Medline (PubMed), and Web of Science. The search terms included combinations of EGFR, mutation, lung cancer, and smoker status or smoking. Papers that were non-original studies, no gene mutation data or unclear smoking status were excluded. A total of 39 studies published between 2004 and 2014 were included in this meta-analysis. The studies were evaluated by two raters for quality. Relative risks (RR) and attributable risk (AR) percentages were computed for associations of EGFR mutations and smoking status in LC.
New Data Findings: From the 39 studies (n = 8442), there were 4887 smokers and 3555 non-smokers with LC. All original studies were of significant results with p values &lt; 0.0001. EGFR wild type was associated with smoking status for all combined race groups (RR = 1.65, 95% CI = 1.51 - 1.80, p &lt; 0.0001, AR = 39.4%, 3792 smokers [77.6%]); whereas, EGFR mutation was associated with non-smoking status (RR = 0.42, 0.34 - 0.51, p &lt; 0.0001, 2024 non-smokers [57.0%]). For sub-group analysis, EGFR wild type was associated with smoking status in Caucasian (RR = 1.50, 95% CI = 1.27 - 1.78, p &lt; 0.0001, AR = 33.5%, 3 studies, 173 smokers [95.1%]), mixed race (RR = 1.58, 95% CI = 1.36 - 1.85, p &lt; 0.0001, AR = 33.5%, 6 studies, 1654 smokers [88.4%]), and Asian (RR = 1.71, 95% CI = 1.52 - 1.92, p &lt; 0.0001, AR = 36.8%, 30 studies, 1965 smokers [69.3%]). The EGFR mutation was associated with non-smoking status in Caucasian (RR = 0.16, 95% CI = 0.08 - 0.31, p &lt; 0.0001, 34 non-smokers [37.8%]), mixed race (RR = 0.26, 95% CI = 1.18 - 0.35, p &lt; 0.0001, 425 non-smokers [51.2%]), and Asian (RR = 0.26, 95% CI = 0.19 - 0.35, p &lt; 0.0001, 1565 non-smokers [59.4%]).
Conclusion: Based on the findings from this meta-analysis, it can be concluded that smoking and EGFR generally have an inversed association. More studies are needed to further document the association of gene environment interaction and epigenetics pathways for LC prevention.
Citation Format: Joyce D. Kusuma, S. Pamela K. Shiao, Hsiao-Ling Chen. Meta-analysis of EGFR and smoking in lung cancer for population health in the global context. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B07.