title: PTEN polymorphisms and the risk of esophageal carcinoma and gastric cardiac carcinoma in a high incidence region of China.
abstract: 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.
authors.affiliation: Hebei Cancer Institute, The Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: H
authors.initials: H
authors.lastname: Ge
authors.forename: Y Y
authors.initials: YY
authors.lastname: Cao
authors.forename: L Q
authors.initials: LQ
authors.lastname: Chen
authors.forename: Y M
authors.initials: YM
authors.lastname: Wang
authors.forename: Z F
authors.initials: ZF
authors.lastname: Chen
authors.forename: D G
authors.initials: DG
authors.lastname: Wen
authors.forename: X F
authors.initials: XF
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Guo
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: J H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics; D017677:Age Distribution; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics; D002299:Cardia / Q000473:pathology; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D016001:Confidence Intervals; D004273:DNA, Neoplasm / Q000032:analysis; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006306:Health Surveys; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011110:Polymorphism, Genetic; D011336:Probability; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D017678:Sex Distribution; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human