PTEN polymorphisms and the risk of esophageal carcinoma and gastric cardiac carcinoma in a high incidence region of China

Dis Esophagus. 2008;21(5):409-15. doi: 10.1111/j.1442-2050.2007.00786.x.


PTEN, as a tumor suppressor gene, plays an important role in regulating cell growth, proliferation, and apoptosis. Two common polymorphisms, -9C/G and IVS4 (-/+), may alter susceptibility to the disease. To test the hypothesis that the genetic variations of PTEN play a role in the etiology of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA), a population-based case-control study was conducted in 350 ESCC patients, 257 GCA patients, and 634 healthy controls from a high-incidence region of Hebei province, China. The PTEN polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). The results showed that the family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age, gender and smoking status adjusted OR = 1.73 and 1.67; 95% CI = 1.29-2.32 and 1.28-2.19, respectively). The overall distribution of the PTEN -9C/G genotype was not significantly different between cancer patients and controls. Compared with the PTEN IVS4-/- genotype, the IVS4+/+ genotype significantly decreased the risk of ESCC and GCA development, the adjusted OR was 0.64 (95% CI = 0.44-0.94) and 0.63 (95% CI = 0.41-0.98), respectively. Stratification analysis by gender, age, smoking status and family history of UGIC showed that the PTEN IVS4-/+ genotype only reduced the risk of ESCC (adjusted OR = 0.55, 95%CI = 0.34-0.90) among subjects with family history of UGIC. While the IVS4+/+ genotype decreased the susceptibility to both ESCC and GCA (adjusted OR = 0.61 and 0.57, 95% CI = 0.37-0.98 and 0.34-0.98, respectively) among male subjects, the IVS4+/+ genotype only decreased the risk of ESCC development among subjects younger than 55 years (adjusted OR = 0.43, 95% CI = 0.21-0.85). In addition, the haplotype analysis found that the -9C/IVS4- haplotype increased the risk of developing ESCC and GCA (OR = 1.31 and 1.24, 95% CI = 1.08-1.58 and 1.001-1.53). Our results suggested that the PTEN IVS4+/+ homozygote may play a protective role in the development of ESCC and GCA, while the haplotype -9C/IVS4- might be the risk factor of the development of ESCC and GCA in the high incidence region population of Hebei province, China.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / genetics
  • Age Distribution
  • Aged
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / genetics
  • Cardia / pathology
  • Chi-Square Distribution
  • China / epidemiology
  • Cohort Studies
  • Confidence Intervals
  • DNA, Neoplasm / analysis
  • Esophageal Neoplasms / epidemiology*
  • Esophageal Neoplasms / genetics*
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Genotype
  • Health Surveys
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Odds Ratio
  • PTEN Phosphohydrolase / genetics*
  • Polymorphism, Genetic
  • Probability
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Assessment
  • Sex Distribution
  • Stomach Neoplasms / epidemiology*
  • Stomach Neoplasms / genetics*


  • DNA, Neoplasm
  • PTEN Phosphohydrolase
  • PTEN protein, human