EGFR mutation status of cell free serum DNA and clinical efficacy of afatinib in pretreated non-small cell lung cancer (NSCLC) harboring EGFR mutations.

Non-small cell lung cancer (NSCLC) is a typical inflammation-associated cancer, and lung adenocarcinoma (LUAD) is the most common histopathological subtype. Epidermal growth factor receptor (EGFR) mutations are the most common driver mutations of LUAD, and they have been identified as important therapeutic targets by EGFR tyrosine kinase inhibitors. Interleukin (IL)-17A secreted by T-helper 17 lymphocytes is a proinflammatory cytokine that plays an important role in cancer pathogenesis. The present study was designed to investigate the possible associations among IL-17A genetic polymorphisms, EGFR mutation status, and the clinicopathologic development of LUAD in a Taiwanese population. Our study population consisted of 277 LUAD patients harboring the wild-type (WT) EGFR or a mutant (MT) EGFR. Four single-nucleotide polymorphisms (SNPs) of IL-17A in the peripheral blood, including rs8193036(C > T), rs8193037(G > A), rs2275913(G > A), and rs3748067(C > T) loci, were genotyped using a TaqMan allelic discrimination assay. Our results showed that none of these IL-17A SNPs were correlated with the risk of developing mutant EGFR. However, patients with a smoking habit who carried the GA genotype of IL-17A rs8193037 had a significantly lower susceptibility to EGFR mutations (adjusted odds ratio (AOR): 0.225; 95% confidence interval (CI): 0.056~0.900, p = 0.035). Moreover, compared to individuals carrying the CC genotype of rs8193036 at IL-17A, T-allele carriers (CT + TT) were at higher risk of developing more-advanced stages (stage III or IV; p = 0.020). In the WT EGFR subgroup analysis, IL-17A rs8193036 T-allele carriers had higher risks of developing an advanced tumor stage (p = 0.016) and lymphatic invasion (p = 0.049). Further analyses of clinical datasets revealed correlations of IL-17 receptor A (IL-17RA) and IL-17RC expressions with a poor prognosis of LUAD patients with a smoking history or with higher levels of tumor-infiltrating lymphocytes. In conclusion, our results suggested that two functional promoter polymorphisms of IL-17A, i.e., rs8193036 and rs8193037, were associated with the EGFR mutation status and progression in LUAD patients, indicating that these two genetic variants might act as possible markers for predicting patients’ clinical prognoses.

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Prevalence and clinicopathological factors of the EGFR mutation status of Vietnamese non-small cell lung cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13120 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13120-e13120

Author(s):

Khoa Trong Mai ◽

Cam Phuong Pham ◽

LUNG TIEN Nguyen ◽

Quynh Thi Thuy Vo ◽

Nguyen TUAN Anh ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Small Cell ◽

Disease Stage ◽

Egfr Mutations ◽

Small Cell Lung ◽

Mutation Status ◽

Nsclc Patients

e13120 Background: To determine the epidermal growth factor receptor ( EGFR) mutation status in non-small cell lung cancer (NSCLC) patients in Vietnamese population at Bach Mai Hospital, and relation of different variables to the frequency of EGFR mutations. Methods: The EGFR mutation status of 1451 tissue samples in NSCLC patients and correlation among different variables of age, gender, smoking habit and histology groups were evaluated. Results: A total of EGFR mutation analysis was performed, with an overall mutation rate of 40.7%. The most prevalent categories were in-frame deletions in exon 19 (57.2% of the overall mutations); followed by L858R and L861Q in exon 21 (35.7%); exon 18 (4,6%); double mutation: 2.9%; The T790M mutation in exon 20 represented approximately 2.5%; The pooled prevalence of EGFR mutation was higher in female (60.6%), non-smokers (61.1%), and patients with adenocarcinoma (42.2%). Conclusions: The prevalence of EGFR mutations of NSCLC in Vietnam is higher than that in the West, but comparably equal to that in some Asian countries. It is associated with female sex, non-smoker status, and adenocarcinoma, sample tissue type and age, but not depends on disease stage and tumor sampling.

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