title: CD24 genetic variants contribute to overall survival in patients with gastric cancer.
abstract: OBJECTIVE
  To investigate the role of single nucleotide polymorphisms (SNPs) in CD24 gene in susceptibility and overall survival of gastric cancer (GC).
  
  
  METHODS
  We genotyped 3 tagging SNPs of CD24-P-534 in the promoter region, P170 in the coding region of exon 2 and P1527 in the 3' untranslated region - using polymerase chain reaction-restriction fragment length polymorphism in specimens from 679 histologically-confirmed GC cases, 111 gastric atrophy (GA) cases and 976 tumor-free controls. Serum immunoglobulin G antibodies to Helicobacter pylori (H. pylori) of all subjects were detected by enzyme-linked immunosorbent assay. CD24 expression was evaluated by immunohistochemistry in 131 GC specimens. Correlations between SNPs and risk of GC or GA were shown by P values and odd ratios (ORs) with 95% confidence intervals (95%CI) compared with the most common genotype of each SNP using the unconditional logistic regression model after adjusting for age, sex and H. pylori infection. Survival within each SNP group was plotted by Kaplan-Meier method and compared by log-rank test (recessive model). Hazard ratios with 95%CIs were computed by Cox regression model after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy.
  
  
  RESULTS
  All of the three loci were in Hardy-Weinberg equilibrium in the control group. Median follow-up time for the 600 GC patients included in the survival analysis was 36.2 mo (range, 2.1-66.7 mo; 95%CI: 34.3-36.5 mo). Patients with the P-534 A/A genotype had significantly shorter survival (HR = 1.38, 95%CI: 1.01-1.88, P = 0.042) than did the C/C or C/A genotype carriers after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. This trend was more evident in patients who lived longer than 2.5 years (HR = 7.55, 95%CI: 2.16-26.32, P = 0.001). The P170 T/T genotype was associated with a shorter lifespan than the non-T/T genotypes, but not significantly so. None of the three genetic variants was found to be associated with risk of GC (including tumor stage, grade and distant metastasis) or with risk of gastric atrophy. Furthermore, no difference of CD24 expression was found among the genotypes.
  
  
  CONCLUSIONS
  The P-534 site in CD24 gene affects the overall survival of gastric cancer and may serve as a prognostic marker for gastric cancer.
authors.affiliation: Zhi-Fang Jia, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Zhi-Fang
authors.initials: ZF
authors.lastname: Jia
authors.affiliation: Zhi-Fang Jia, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Li-Zhong
authors.initials: LZ
authors.lastname: Wang
authors.affiliation: Zhi-Fang Jia, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Xue-Yuan
authors.initials: XY
authors.lastname: Cao
authors.affiliation: Zhi-Fang Jia, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Zhi-Fang Jia, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Cao
authors.affiliation: Zhi-Fang Jia, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wu
authors.affiliation: Zhi-Fang Jia, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: You
authors.affiliation: Zhi-Fang Jia, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Mei-Shan
authors.initials: MS
authors.lastname: Jin
authors.affiliation: Zhi-Fang Jia, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Yin-Ping
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Zhi-Fang Jia, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Bao-Sen
authors.initials: BS
authors.lastname: Zhou
authors.affiliation: Zhi-Fang Jia, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D051927:CD24 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D005091:Exons; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human
keywords: CD24; Gastric atrophy; Gastric cancer; Overall survival; Single nucleotide polymorphisms