Genetic variations in SLC3A2/CD98 gene as prognosis predictors in non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) is characterized by poor prognosis and only a few molecular markers may be potentially used to predict the risk of progression. This study aims to assess the effects of single nucleotide polymorphisms (SNPs) in the CD98 gene on prognosis of NSCLC patients. We genotyped three potential functional SNPs in CD98 gene using Sequenom iPLEX genotyping system in a cohort of 482 NSCLC patients. Multivariate cox proportional hazards model and Kaplan-Meier curve were used for the survival analysis. The variant-containing genotypes of rs1059292 in 5'-flanking region of CD98 gene were significantly associated with an increased risk of death in the multivariate analysis (Hazard ratio [HR], 1.49; 95% confidence interval [95% CI]: 1.04-2.14 in a dominant model). In stratified analysis, the association remained significant in patients with poor differentiation (HR=1.81, 95% CI=1.01-3.25). In addition, rs1059292 also showed a borderline significant association with T stage (OR=1.49; 95% CI: 0.96-2.35) and N stage (OR=1.53; 95% CI: 0.98-2.39). Functional analysis demonstrated that variant genotype of SNP rs1059292 significantly enhanced the transcription activity of CD98 gene promoter. Our data suggest that genetic variation of rs1059292 in CD98 gene may affect clinical outcome of NSCLC in Chinese population.
State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical University, Xi'an, P. R., China.
Xu
X
Guo
State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical University, Xi'an, P. R., China.
Hongwei
H
Li
State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical University, Xi'an, P. R., China.
Fei
F
Fei
Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, P. R., China.
Boya
B
Liu
Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, P. R., China.
Xiaofei
X
Li
Division of Population Science, Department of Medical Oncology, Kimmel Cancer, Thomas Jefferson University, Philadelphia, Pennsylvania.
Hushan
H
Yang
State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical University, Xi'an, P. R., China.
Zhinan
Z
Chen
State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical University, Xi'an, P. R., China.
Jinliang
J
Xing
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000208:ethnology / Q000235:genetics*; D002681:China; D005260:Female; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
D014408:Biomarkers, Tumor; D027282:Fusion Regulatory Protein 1, Heavy Chain; C545989:SLC3A2 protein, human
CD98; NSCLC; prognosis; single nucleotide polymorphism