Abstract
Tyrosine kinase inhibitor- (TKI-) based therapy revolutionized the overall survival and the quality of life in non-small-cell lung cancer (NSCLC) patients that have epidermal growth factor receptor (EGFR) mutations. However, EGFR is a highly polymorphic and mutation-prone gene, with over 1200 single nucleotide polymorphisms (SNPs). Since the role of EFGR polymorphism on the treatment outcome is still a matter of debate, this research analyzed the available literature data, according to the PRISMA guidelines for meta-analyses. Research includes PubMed, Scopus, ISI Web of Science, and 14 of genome-wide association studies (GWAS) electronic databases in order to provide quantitative assessment of the association between ten investigated EGFR SNPs and the survival of NSCLC patients. The pooled HR and their 95% CI for OS and PFS for different EGFR polymorphisms using a random or fixed effect model based on the calculated heterogeneity between the studies was applied. The longest and the shortest median OSs were reported for the homozygous wild genotype and a variant allele carriers for rs712829 (-216G>T), respectively. Quantitative synthesis in our study shows that out of ten investigated EGFR SNPs (rs11543848, rs11568315, rs11977388, rs2075102, rs2227983, rs2293347, rs4947492, rs712829, rs712830, and rs7809028), only four, namely, rs712829 (-216G>T), rs11568315 (CA repeat), rs2293347 (D994D), and rs4947492, have been reported to affect the outcome of TKI-based NSCLC treatment. Of these, only -216G>T and variable CA repeat polymorphisms have been confirmed by meta-analysis of available data to significantly affect OS and PFS in gefitinib- or erlotinib-treated NSCLC patients.
Highlights
For the past several decades, lung cancer remains one of the major causes of mortality worldwide [1,2,3]
To identify the studies on the association between epidermal growth factor receptor gene (EGFR) polymorphisms and the survival in non-small-cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitor (TKI) therapy, a systematic search of the available literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for metaanalyses and systematic reviews was performed [34]. ree electronic databases, namely, PubMed [35], Scopus [36], and ISI Web of Science [37], were thoroughly explored, with a search query consisting of a specific combination of subject headings and text words
Of 5467 records obtained through the screening of PubMed, ISI WOS, Scopus, and 14 genome-wide association studies (GWAS) databases, 3699 remained after removing the duplicates
Summary
For the past several decades, lung cancer remains one of the major causes of mortality worldwide [1,2,3]. According to the World Health Organization, it is the most commonly diagnosed cancer and the leading cause of cancer death, with over 2 million of new cases and more than 1.7 million deaths in 2018 [4, 5]. Cigarette smoking represents the primary risk factor for NSCLC development [8], numerous investigations confirmed that genetics plays one of the leading roles in the process [9,10,11]. Gene variations that have been identified as conferring higher risk of NSCLC could be either germline or somatic, with some of the most common lung cancer-related driver mutations linked to epidermal growth factor receptor gene (EGFR) [12]
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