Potential Impacts of Interleukin-17A Promoter Polymorphisms on the EGFR Mutation Status and Progression of Non-Small Cell Lung Cancer in Taiwan

doi:10.3390/genes12030427

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23460

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題名:	Potential Impacts of Interleukin-17A Promoter Polymorphisms on the EGFR Mutation Status and Progression of Non-Small Cell Lung Cancer in Taiwan
作者:	Lee, KL;Lai, TC;Wang, YC;Shih, PC;Yang, YC;Tsao, TCY;Liu, TC;Wen, YC;Chang, LC;Yang, SF;Chien, MH
關鍵詞:	interleukin 17A;polymorphism;epidermal growth factor receptor;mutation;lung adenocarcinoma
日期:	2021
上傳時間:	2022-08-05T09:37:38Z (UTC)
出版者:	MDPI
摘要:	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.
URI:	http://dx.doi.org/10.3390/genes12030427 https://www.webofscience.com/wos/woscc/full-record/WOS:000633669500001 https://ir.csmu.edu.tw:8080/handle/310902500/23460
關聯:	GENES ,2021,v12,issue 3
顯示於類別:	[中山醫學大學研究成果] 期刊論文

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