title: RACK1 is a candidate gene associated with the prognosis of patients with early stage non-small cell lung cancer.
abstract: BACKGROUND
  This study was conducted to identify genetic polymorphisms associated with the prognosis of patients with early stage NSCLC.
  
  
  METHODS
  We genotyped 1,969 potentially functional single nucleotide polymorphisms (SNPs) of 1,151 genes involved in carcinogenesis in 166 NSCLC patients who underwent curative surgery, using the Affymetrix custom-made GeneChip. A replication study was performed in an independent cohort of 626 patients.
  
  
  RESULTS
  Fifty six SNPs which were associated with both overall survival (OS) and disease-free survival (DFS) with log-rank P values < 0.05 in discovery set were selected for validation. Among those, five SNPs (RACK1 rs1279736C>A and rs3756585T>G, C3 rs2287845T>C, PCAF rs17006625A>G, and PCM1 rs17691523C>G) were found to be significantly associated with survival in the same direction as the discovery set. In combined analysis, the rs1279736C>A and rs3756585T>G were most significantly associated with OS and DFS in multivariate analysis (P for OS = 4 × 10⁻⁵ and 7 × 10⁻⁵, respectively; and P for DFS = 0.003, both; under codominant model). In vitro promoter assay and electrophoretic mobility shift assay revealed that the rs3756585 T-to-G change increased promoter activity and transcription factor binding of RACK1.
  
  
  CONCLUSIONS
  We identified five SNPs, especially RACK1 rs3756585T>G, as markers for prognosis of patients with surgically resected NSCLC.
authors: Departments of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Republic of Korea.
authors: Yi-Young
authors: YY
authors: Choi
authors: Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.|Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors: Shin Yup
authors: SY
authors: Lee
authors: Biostatistics Center, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors: Won Kee
authors: WK
authors: Lee
authors: Departments of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Republic of Korea.|Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors: Hyo-Sung
authors: HS
authors: Jeon
authors: Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.|Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors: Eung Bae
authors: EB
authors: Lee
authors: Diagnosis and Prediction Biotechnology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors: Hyun Cheol
authors: HC
authors: Lee
authors: Departments of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Republic of Korea.|Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors: Jin Eun
authors: JE
authors: Choi
authors: Departments of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Republic of Korea.
authors: Hyo-Gyoung
authors: HG
authors: Kang
authors: Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors: Eun Jin
authors: EJ
authors: Lee
authors: Departments of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Republic of Korea.
authors: Eun Young
authors: EY
authors: Bae
authors: Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.|Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors: Seung Soo
authors: SS
authors: Yoo
authors: Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors: Jaehee
authors: J
authors: Lee
authors: Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors: Seung Ick
authors: SI
authors: Cha
authors: Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors: Chang Ho
authors: CH
authors: Kim
authors: Departments of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Republic of Korea.
authors: In-San
authors: IS
authors: Kim
authors: Diagnosis and Prediction Biotechnology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors: Myung Hoon
authors: MH
authors: Lee
authors: Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Republic of Korea.
authors: Young Tae
authors: YT
authors: Kim
authors: Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Republic of Korea.
authors: Sanghoon
authors: S
authors: Jheon
authors: Departments of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Republic of Korea.|Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.|Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors: Jae Yong
authors: JY
authors: Park
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins