Effect of WW Domain-Containing Oxidoreductase Gene Polymorphism on Clinicopathological Characteristics of Patients with EGFR Mutant Lung Adenocarcinoma in Taiwan

Abstract

Lung adenocarcinoma is the most common histological type of non-small cell lung cancer, which accounts for the majority of lung cancers. Previous studies have showed that dysregulation of WW domain-containing oxidoreductase (WWOX) participates in the generation of several cancer types, including lung cancer. However, whether these WWOX polymorphisms are related to the clinical risk of epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma is worthy of investigation. The present study examined the relationship between the WWOX single-nucleotide polymorphisms (SNPs; rs11545028, rs12918952, rs3764340, rs73569323, and rs383362) and the clinicopathological factors in lung adenocarcinoma patients with or without EGFR mutations. We found that there was no significant difference in the genotype distribution of WWOX polymorphism between EGFR wild-type and EGFR mutant in patients with lung adenocarcinoma. Our results demonstrated that the presence of at least one G genotype (CG and GG) allele on WWOX rs3764340 was associated with a significantly higher risk of nearby lymph node involvement in those patients harboring EGFR mutations (odds ratio (OR) = 3.881, p = 0.010) compared with the CC genotype. Furthermore, in the subgroup of lung adenocarcinoma patients with the EGFR-L858R mutation, both WWOX rs3764340 C/G (OR = 5.209, p = 0.023) and rs73569323 C/T polymorphisms (OR = 3.886, p = 0.039) exhibited significant associations with the size of primary tumors and the invasion of adjacent tissues. In conclusion, these data indicate that WWOX SNPs may help predict tumor growth and invasion in patients with EGFR mutant lung adenocarcinoma, especially those with the EGFR-L858R mutant in Taiwan.

WWOX Polymorphisms as Predictors of the Biochemical Recurrence of Localized Prostate Cancer after Radical Prostatectomy

“…Several studies have consistently revealed prominent associations between the polymorphisms of WWOX and the aggressive, poor prognosis of various malignancies, such as urothelial, esophageal squamous cell, hepatocellular, lung, pancreatic, and thyroid cancers 30 , 31 , 36 - 41 . To the best of our knowledge, the present study is the first to investigate the association between the polymorphisms of WWOX and the clinicopathologic features of resectable PCa in Taiwanese men.…”

“…Several genetic polymorphisms have been associated with PSA level, tumor susceptibility, tumor grade, and mortality in PCa [21][22][23][24][25][26][27]. Moreover, WWOX SNPs have been reported in numerous cancers [28][29][30][31][32]. However, the association between the polymorphism of WWOX and the risk of the postoperative BCR of PCa remains unclear.…”

Genetic Associations of Visfatin Polymorphisms with EGFR Status and Clinicopathologic Characteristics in Lung Adenocarcinoma

“…Epidermal growth factor receptor ( EGFR ) mutations in the tyrosine kinase domain are common in NSCLC patients, with higher rates particularly in those with adenocarcinoma, non-smokers, females, and Asian populations [ 5 , 6 ]. Around two-thirds (67.1%) of patients with EGFR -mutant NSCLC have classical EGFR mutations (exon 21 L858R point mutation or exon 19 deletions [Ex19del]) [ 7 ].…”

“…Given the important role of EGFR mutation status in NSCLC development, we decided to explore interactions amongst crucial genes and EGFR status in NSCLC and LUAD. Interleukin-17A, the tumor suppressor protein WW domain-containing oxidoreductase, tissue inhibitor of metalloproteinase 3 (TIMP3), and long noncoding RNA H19 polymorphisms have all been associated with clinicopathologic characteristics in lung cancers [ 5 , 9 , 12 , 13 ]. These four studies have helped to identify subgroups of patients at high risk for LUAD progression.…”