Interactions between Glutathione-S-Transferase M1, T1 and P1 polymorphisms and smoking, and increased susceptibility to esophageal squamous cell carcinoma.
BACKGROUND
A complex of genetic and environmental factors is involved in carcinogenesis of the esophageal squamous cell carcinoma (ESCC). Glutathione-S-Transferases (GSTs) are phase-II enzymes playing role in detoxification of carcinogen electrophiles. Genetic polymorphisms of GSTM1, GSTT1 and GSTP1 in association with some environmental factors and their impact on esophageal cancer susceptibility were assessed in the Iranian population.


METHODS
Genomic DNA of peripheral blood leukocytes from 148 confirmed esophageal cancer cases and 137 healthy individuals as control group was assayed for restriction fragment length polymorphisms in the GSTP1 loci by PCR amplification followed by digestion with Alw26I. Deletion of the GSTM1 and GSTT1 genes was detected by multiplex PCR. A data-mining method based on decision trees was applied to produce a predictive model of interactions between genotypes.


RESULTS
Smoking was independently associated with ESCC (p<0.05, OR: 2.286, 95% CI=1.311-3.983). Smoking along with GSTP1 Val/Val genotype was associated to ESCC (p<0.001, OR: 3.886, 95% CI=1.830-8.251), while non-smokers with GSTP1 Val/Val were significantly more frequent in non-cancerous group. (p=0.007, OR: 0.507, 95% CI=0.309-0.830).


CONCLUSIONS
Data-mining methods are useful tools to map out a scheme for predicting complex relations and combinations of different genotypes. Genotyping analysis of GSTP1 together with assessment of smoking seems to be important in determining the risk of ESCC in the Iranian population.
Moaven
Omeed
O
Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Raziee
Hamid Reza
HR
Sima
Hamid Reza
HR
Ganji
Azita
A
Malekzadeh
Reza
R
A'rabi
Azadeh
A
Abdollahi
Abbas
A
Memar
Bahram
B
Sotoudeh
Masoud
M
Naseh
Hossein
H
Nekoui
Navid
N
Razavipour
Adeleh
A
Gholamin
Mehran
M
Dadkhah
Ezzat
E
Farshchian
Moein
M
Abbaszadegan
Mohammad Reza
MR
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics; D003663:Decision Trees; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1