title: Influence of the KDM4A rs586339 polymorphism on overall survival in Asian non-small-cell lung cancer patients.
abstract: The critical role of lysine demethylase 4A (KDM4A), in regulating chromatin structure and consequently in driving cellular proliferation and oncogenesis has been the focus of recent studies. Non-small-cell lung cancer (NSCLC) patients with adenocarcinoma histology who were homozygous for KDM4A single nucleotide polymorphism (SNP)-A482 (rs586339) were recently shown to have significantly worse overall survival (OS) compared with patients with the wild-type or the heterozygous genotype at this locus (hazard ratio=1.68, P=0.042). In the current study, we investigated the association between the same polymorphism with OS in our Asian NSCLC-adenocarcinoma patients comprising Chinese (N=572), Malays (N=50), and Indians (N=22). KDM4A SNP-A482 genotype status was determined by Sanger sequencing. OS was calculated from the date of diagnosis to date of death or censored at the date of last follow-up. Kaplan-Meier analysis, log-rank test, and Cox regression methods were utilized to evaluate OS outcomes. KDM4A SNP-A482 had a minor allele (C) frequency of 18.8% and a major allele (A) frequency of 81.2% in our Asian NSCLC (adenocarcinoma) patients. However, the OS in our Asian NSCLC patients homozygous for KDM4A SNP-A482 was not significantly different from those who were wild type or heterozygous at this locus [CC vs. AA/AC: median OS (95% confidence interval): 40.2 (18.7-61.6) vs. 29.6 (26.9-32.3) months; P=0.858]. The results remained statistically nonsignificant even after adjustment for epidermal growth factor receptor mutational status, suggesting that KDM4A SNP-A482 does not significantly influence OS in Asian NSCLC patients.
authors.affiliation: aLaboratory of Clinical Pharmacology, Division of Medical Sciences, Humphrey Oei Institute of Cancer Research bNational Cancer Centre, Division of Medical Oncology cClinical Pharmacology, SingHealth dDepartment of Clinical Sciences, Duke-NUS Medical School, Singapore.
authors.forename: Charlie
authors.initials: C
authors.lastname: Marvalim
authors.forename: Jing Xiang Gimson
authors.initials: JX
authors.lastname: Wong
authors.forename: Natalia
authors.initials: N
authors.lastname: Sutiman
authors.forename: Wan Teck
authors.initials: WT
authors.lastname: Lim
authors.forename: Shao Weng
authors.initials: SW
authors.lastname: Tan
authors.forename: Ravindran
authors.initials: R
authors.lastname: Kanesvaran
authors.forename: Quan Sing
authors.initials: QS
authors.lastname: Ng
authors.forename: Amit
authors.initials: A
authors.lastname: Jain
authors.forename: Mei Kim
authors.initials: MK
authors.lastname: Ang
authors.forename: Wan Ling
authors.initials: WL
authors.lastname: Tan
authors.forename: Chee Keong
authors.initials: CK
authors.lastname: Toh
authors.forename: Eng Huat
authors.initials: EH
authors.lastname: Tan
authors.forename: Balram
authors.initials: B
authors.lastname: Chowbay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000208:ethnology* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000208:ethnology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D016019:Survival Analysis
chemical_list: D056484:Jumonji Domain-Containing Histone Demethylases; C494424:KDM4A protein, human