title: Genome-wide association study identifies common variants in SLC39A6 associated with length of survival in esophageal squamous-cell carcinoma.
abstract: We conducted a genome-wide scan of SNPs to identify variants associated with length of survival in 1,331 individuals with esophageal squamous-cell carcinoma (ESCC), with associations validated in 2 independent sets including 1,962 individuals with this cancer. We identified rs1050631 in SLC39A6 as associated with the survival times of affected individuals, with the hazard ratio for death from ESCC in the combined sample being 1.30 (95% confidence interval (CI) = 1.19-1.43; P = 3.77 × 10(-8)). rs7242481, located in the 5' UTR of SLC39A6, disturbs a transcriptional repressor binding site and results in upregulation of SLC39A6 expression. Immunohistochemical staining of ESCC tissues showed that higher expression of SLC39A6 protein was correlated with shorter length of survival in individuals with advanced ESCC (P = 0.013). Knockdown of SLC39A6 expression suppressed proliferation and invasion in ESCC cells. These results suggest that SLC39A6 has an important role in the prognosis of ESCC and may be a potential therapeutic target.
authors: State Key Laboratory of Molecular Oncology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors: Chen
authors: C
authors: Wu
authors: Dong
authors: D
authors: Li
authors: Weihua
authors: W
authors: Jia
authors: Zhibin
authors: Z
authors: Hu
authors: Yifeng
authors: Y
authors: Zhou
authors: Dianke
authors: D
authors: Yu
authors: Tong
authors: T
authors: Tong
authors: Mingrong
authors: M
authors: Wang
authors: Dongmei
authors: D
authors: Lin
authors: Yan
authors: Y
authors: Qiao
authors: Yuling
authors: Y
authors: Zhou
authors: Jiang
authors: J
authors: Chang
authors: Kan
authors: K
authors: Zhai
authors: Menghan
authors: M
authors: Wang
authors: Lixuan
authors: L
authors: Wei
authors: Wen
authors: W
authors: Tan
authors: Hongbing
authors: H
authors: Shen
authors: Yixin
authors: Y
authors: Zeng
authors: Dongxin
authors: D
authors: Lin
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002874:Chromosome Mapping; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D055106:Genome-Wide Association Study; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D027682:Cation Transport Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C418627:SLC39A6 protein, human
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