Modification effects of GSTM1, GSTT1 and CYP2E1 polymorphisms on associations between raw salted food and incomplete intestinal metaplasia in a high-risk area of stomach cancer

Int J Cancer. 2004 Feb 10;108(4):606-12. doi: 10.1002/ijc.11535.


Incomplete intestinal metaplasia (IM) is a precursor of stomach cancer. To identify risk factors of incomplete IM, a 2-stage survey was carried out in 1995 among 1,485 residents in Matzu, an area with highest mortality from stomach cancer in Taiwan. There were 312 study subjects including 174 men and 138 women sampled for the gastroendoscopic examination of IM. Information on personal and familial history of stomach cancer, cigarette smoking, alcohol consumption and intake frequency of various salted food items were obtained by personal interview based on a structured questionnaire. Blood samples were collected from each participant. Four biopsies per subject were taken from all subjects at gastroendoscopic examination to diagnose the status of IM pathologically. The Helicobacter pylori in biopsies was detected by the histomorphological or immunochemistry method, and antibodies against H. pylori in serum by the enzyme-linked immunosorbent assay. Plasma level of selenium was determined by atomic absorption spectrometry, plasma level of retinol, alpha-tocopherol, alpha-carotene, and beta-carotene by high performance liquid chromatography, genotypes of glutathione S-transferase (GST) M1 and T1 and cytochrome P450 (CYP) 2E1 by polymerase chain reaction. The significant association between history of stomach cancer among first-degree relatives and incomplete IM was found (odds ratio [OR] = 2.50; 95% confidence interval [CI] = 1.15-5.43). There was no association between H. pylori infection and incomplete IM. Alcohol drinkers for >20 years had an elevated risk compared to non-drinkers (OR = 3.34; 95% CI = 1.19-9.39). No associations between incomplete IM and plasma levels of selenium, retinol, alpha-tocopherol, alpha-carotene and beta-carotene were found. Salted food including salted meat, dehydrated salted vegetables and raw salted seafood consumed at ages of </=15 and 16-30 years old was associated with an increased IM risk with OR ranging from 2-3. More striking associations between incomplete IM and salted food intake were observed among subjects with genotypes of GSTM1 null, GSTT1 non-null and CYP2E1 c1/c1. Our study suggests the importance of gene-environment interaction on the development of incomplete IM.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Cytochrome P-450 CYP2E1 / genetics*
  • Female
  • Genotype
  • Glutathione Transferase / genetics*
  • Humans
  • Intestines / enzymology
  • Intestines / pathology*
  • Male
  • Metaplasia
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics
  • Risk Factors
  • Selenium / metabolism
  • Sodium, Dietary / adverse effects*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / epidemiology
  • Stomach Neoplasms / etiology*
  • Taiwan / epidemiology
  • alpha-Tocopherol / metabolism
  • beta Carotene / metabolism


  • Sodium, Dietary
  • beta Carotene
  • Cytochrome P-450 CYP2E1
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1
  • alpha-Tocopherol
  • Selenium