title: Association of CD14/-260 polymorphism with gastric cancer risk in Highland Tibetans.
abstract: OBJECTIVE
  To investigate the relationship between CD14-260 and -651 polymorphisms and the risk of developing gastric cancer.
  
  
  METHODS
  DNA was extracted from peripheral blood samples obtained from 225 Tibetans with gastric cancer and 237 healthy Tibetans, and analyzed using the polymerase chain reaction/ligase detection (PCR/LDR) method to determine the genotypes at -260 and -651 loci of the CD14 promoter. The allele frequencies, genotype frequencies, and haplotypes were analyzed for their association with gastric cancer risk using online SHEsis software. The luciferase reporter assay and point mutation analysis were used to construct in vitro plasmids expressing a C/T homozygote at the -260 locus of the CD14 promoter.
  
  
  RESULTS
  The frequencies of CC, CT and TT genotypes in the CD14-260 C/T locus in gastric cancer patients were 19.1%, 38.7% and 42.2%, respectively, whereas they were 33.3%, 32.5% and 34.2%, respectively, in healthy control subjects. CT genotype carriers were more frequently found among gastric cancer patients than healthy controls (OR = 2.076; 95%CI: 1.282-3.360). Also, TT genotype carriers were more frequently found among gastric cancer patients (OR = 2.155; 95%CI: 1.340-3.466). Compared to the C allele of CD14/-260, the T allele was associated with an increased risk for gastric cancer (OR = 1.574; 95%CI: 1.121-2.045). Furthermore, the frequencies of CC, CT and TT in the CD14-651 C/T locus in gastric cancer patients were 64.4%, 29.3% and 6.2%, respectively, while they were 56.5%, 35.0% and 8.4%, respectively, in the healthy control subjects (P > 0.05). Data obtained using the luciferase reporter assay showed that the p260T homozygote was associated with greater CD14 promoter activity (P < 0.01).
  
  
  CONCLUSIONS
  CD14/-260 polymorphism is associated with gastric cancer risk in Highland Tibetans and affects CD14 promoter activity, thereby regulating CD14 expression.
authors.affiliation: Kang Li, Zeng Dan, Xue-Jun Hu, Luo-Bu Gesang, Department of Gastroenterology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, Tibet Autonomous Region, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.affiliation: Kang Li, Zeng Dan, Xue-Jun Hu, Luo-Bu Gesang, Department of Gastroenterology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, Tibet Autonomous Region, China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Dan
authors.affiliation: Kang Li, Zeng Dan, Xue-Jun Hu, Luo-Bu Gesang, Department of Gastroenterology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, Tibet Autonomous Region, China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Hu
authors.affiliation: Kang Li, Zeng Dan, Xue-Jun Hu, Luo-Bu Gesang, Department of Gastroenterology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, Tibet Autonomous Region, China.
authors.forename: Luo-Bu
authors.initials: LB
authors.lastname: Gesang
authors.affiliation: Kang Li, Zeng Dan, Xue-Jun Hu, Luo-Bu Gesang, Department of Gastroenterology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, Tibet Autonomous Region, China.
authors.forename: Yong-Ge
authors.initials: YG
authors.lastname: Ze
authors.affiliation: Kang Li, Zeng Dan, Xue-Jun Hu, Luo-Bu Gesang, Department of Gastroenterology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, Tibet Autonomous Region, China.
authors.forename: Zha-Xi
authors.initials: ZX
authors.lastname: Bianba
authors.affiliation: Kang Li, Zeng Dan, Xue-Jun Hu, Luo-Bu Gesang, Department of Gastroenterology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, Tibet Autonomous Region, China.
authors.forename: Cuo-Mu
authors.initials: CM
authors.lastname: Ciren
authors.affiliation: Kang Li, Zeng Dan, Xue-Jun Hu, Luo-Bu Gesang, Department of Gastroenterology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, Tibet Autonomous Region, China.
authors.forename: Yu-Qiang
authors.initials: YQ
authors.lastname: Nie
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D018609:Tibet / Q000453:epidemiology; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D018950:Lipopolysaccharide Receptors
keywords: CD14; Cancer susceptibility; Gastric cancer; Single nucleotide polymorphisms; Tibetans