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This study aims to investigate the association of five single nucleotide polymorphisms ( SNPs) in the phosphatase and tensin homologue ( PTEN) gene and additional role of gene-gene interaction with esophageal squamous cell carcinoma ( ESCC), based on a Chinese case-control study. A total of 871 subjects (420 males and 451 females) were selected, including 425 ESCC cases and 446 controls. Five SNPs were selected for genotyping in the case-control study: rs2735343, rs555895, rs2299939, rs17431184 and rs701848. Logistic regression model was used to examine the association between five SNP and ESCC, and additional interaction among five SNP, odds ratio ( OR) and 95% confident interval (95% CI) were calculated. All genotypes were distributed according to Hardy- Weinberg equilibrium in controls. The carriers of homozygous mutant of rs2735343 and rs701848 polymorphism revealed increased ESCC risk than those with wild-type homozygotes, and OR (95% CI) were 1.27 (1.09-2.08) and 1.45 (1.17-1.98), respectively. We also found a potential gene-gene interaction between rs2735343 and rs701848 ( P = 0.0010), and a potential gene-gene interaction among all five SNP ( P = 0.0107) after covariates adjustment. Subjects with TC or CC of rs2735343 and TC or CC of rs701848 genotype have highest ESCC risk, compared to subjects with TT of rs2735343 and TT of rs701848 genotype, OR (95% CI) was 2.76 (1.37-3.45) after covariates adjustment. The carriers of homozygous mutant of rs2735343 and rs701848 polymorphism revealed increased ESCC risk. We also found a potential gene-gene interaction between rs2735343 and rs701848 and a potential gene-gene interaction among all five SNPs. [ABSTRACT FROM AUTHOR]

Aberrant DNA methylation of promoter region CpG islands may serve as an alternative mechanism to genetic defects in the inactivation of tumor suppressor genes ( TSGs) in human malignancies. The aim of this study was to examine the promoter methylation status of the PTEN TSG and its association with esophageal squamous cell carcinoma ( ESCC) carcinogenesis in a Chinese Kazakh population, which is known to have a relatively high ESCC incidence and mortality. The methylation status of the PTEN promoter region was determined in patients with ESCC ( n = 95) and healthy individuals ( n = 65) using highly sensitive Sequenom Epityper assays. The methylation level of the PTEN gene was significantly higher in patients with ESCC than in healthy controls. The median methylation level was 10.0% (interquartile range [ IQR]: 7.0-11.0%) in patients with ESCC and 6.0% in controls ( IQR: 4.0-9.0%; P = 0.001). PTEN methylation levels were higher in male patients with ESCC than in male controls, whereas a trend toward significance was observed between female patients with ESCC and female controls ( P = 0.005 and P = 0.086, respectively). The PTEN methylation level was associated with histopathological grade and lymph node metastasis in patients with ESCC ( P = 0.002 and P = 0.009, respectively). To our knowledge, this is the first report to show the presence of PTEN promoter CpG hypermethylation in ESCC and its association with tumor metastasis. [ABSTRACT FROM AUTHOR]