title: Polymorphisms in chemokine and receptor genes and gastric cancer risk and survival in a high risk Polish population.
abstract: OBJECTIVE
  To examine if genetic variations in chemokine receptor and ligand genes are associated with gastric cancer risk and survival.
  
  
  METHODS
  The study included 298 cases and 417 controls from a population-based study of gastric cancer conducted in Warsaw, Poland in 1994-1996. We investigated seven single nucleotide polymorphisms in a chemokine ligand (CXCL12) and chemokine receptor (CCR2, CCR5, CX3CR1) genes and one frameshift deletion (CCR5) in blood leukocyte DNA in relation to gastric cancer risk and survival. Genotyping was conducted at the NCI Core Genotyping Facility. Odds ratios and 95% confidence intervals were computed using univariate and multivariate logistic regression models. Survival analysis was performed using Cox proportional hazards models.
  
  
  RESULTS
  Gastric cancer risk was not associated with single chemokine polymorphisms. A CCR5 haplotype that contained the common alleles of IVS1+151 G>T (rs2734648), IVS2+80 C>T (rs1800024) and minor allele of IVS1+246 A>G (rs1799987) was associated with a borderline significantly increased risk (OR = 1.5, 95% CI: 1.0?2.2). For gastric cancer cases, there was a greater risk of death for carriers of the minor alleles of CCR2 Ex2+241 G>A (rs1799864) (HR = 1.5, 95% CI: 1.1-2.1) and CCR5 IVS2+80 C>T (rs1800024) (HR = 1.5, 95% CI: 1.1-2.1). Carriers of the CCR5 minor allele of IVS1+151 G>T (rs2734648) had a decreased risk of death compared to homozygote carriers of the common allele (HR = 0.8, 95% CI: 0.6-1.0).
  
  
  CONCLUSIONS
  Our findings do not support an association between gastric cancer risk and single chemokine genetic variation. The observed associations between cancer risk and a CCR5 haplotype and between survival and polymorphisms in CCR2 and CCR5 need replication in future studies.
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N. Lake Shore Drive, Chicago, IL 60611, USA. agawron@northwestern.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gawron
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Fought
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.forename: Laura E
authors.initials: LE
authors.lastname: Beane Freeman
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
mesh_terms: D000328:Adult; D000368:Aged; D000073883:CX3C Chemokine Receptor 1; D054426:Chemokine CXCL2 / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D054390:Receptors, CCR2 / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D012306:Risk; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054426:Chemokine CXCL2; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine