title: Genetic association of osteopontin (OPN) and its receptor CD44 genes with susceptibility to Chinese gastric cancer patients.
abstract: OBJECTIVE
  (1) To investigate associations between single nucleotide polymorphisms (SNPs) in osteopontin (OPN) and its receptor-cluster of differentiation 44 (CD44) genes and gastric cancer susceptibility. (2) To explore the correlation of OPN and CD44 expression of gastric cancer.
  
  
  METHODS
  We detected 26 SNPs of the genes in gastric cancer patients from the Chinese Han population by Sequenom technique and performed expression of OPN in combination with CD44 in 243 tissues samples of the cases by tissue microarray and immunohistochemistry (IHC).
  
  
  RESULTS
  We found that the minor alleles of OPN rs4754C>T and OPN rs9138C>A remained strongly associated with decreased gastric cancer risk (P = 1.53 × 10(-4), odds ratio (OR) 0.642, 95 % confidence interval (CI) 0.511-0.808 and P = 1.59 × 10(-4), OR 0.642, 95 %CI 0.510-0.809). OPN variant rs1126772A>G and CD44 variant rs353639A>C significantly contributed to elevated risk of gastric cancer (P = 0.042, OR 1.279, 95 % CI 1.008-1.622 and P = 0.047, OR 1.334, 95 % CI 1.003-1.772). Haplotypes of OPN and CD44 variants significantly influenced risk of gastric cancer. Clinical data indicated that rs4754 and rs9138 of OPN were significantly associated with smoking (P = 0.029, OR 0.343, 95 % CI 0.127-0.926 and P = 0.029, OR 0.343, 95 %CI 0.127-0.926) and OPN rs1126772 revealed associations with tumor-node-metastasis (TNM) stage (P = 0.025, OR 1.765, 95 % CI 1.073-2.905) and tumor differentiation (P = 0.031, OR 1.722, 95 % CI 1.049-2.825). OPN expression was observed in 133 of the 243 cases (54.7 %) by IHC and was correlated with serosa invasion (P = 0.013), TNM stage (P = 0.003) and lymph node metastasis (P = 0.002). CD44 expression was found in 92 of the 243 cases (37.9 %) and was associated with tumor size (P = 0.005) and lymph node metastasis (P = 0.023), respectively. The OPN expression displayed a positive association with CD44 (P = 0.01, r s = 0.164).
  
  
  CONCLUSIONS
  We found that the polymorphisms rs4754, rs9138 and rs1126772 of OPN gene and rs353639 of CD44 gene were significantly associated with gastric cancer. Our IHC data indicated that interaction of OPN and CD44 protein would promote progression and metastasis of gastric cancer.
authors.affiliation: Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qiu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hu
authors.forename: Zuo-Yang
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.forename: Fei-Hong
authors.initials: FH
authors.lastname: Xu
authors.forename: Marion E
authors.initials: ME
authors.lastname: Schneider
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Ma
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Du
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Zuo
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Xu-Shi
authors.initials: XS
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hong-Zhen
authors.initials: HZ
authors.lastname: Xia
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Wu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Du
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D053495:Osteopontin