Gastric carcinogenesis: Possible role of polymorphisms of GSTM1, GSTT1, and GSTP1 genes.
OBJECTIVE
Although Helicobacter pylori infection is associated with gastric cancer (GC), only 1% of patients develop a malignancy, which suggests a role of host genetic factors. The aim of this study was to investigate the role of polymorphisms of GSTM1, GSTT1, and GSTP1 genes, which encode for carcinogen-detoxifying enzymes, in gastric mutagenesis.


METHODS
Genotyping of GSTT1 and GSTM1 was done using PCR, while PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) was used for genotyping of GSTP1 in 76 patients with gastric neoplasm (GN), 67 with non-ulcer dyspepsia (NUD), 44 with peptic ulcer (PU), and 100 healthy controls (HC).


RESULTS
The study population included: GN (intestinal 40 (53%), diffuse 26 (34%), primary gastric lymphoma 8 (11%) and unclassified 2 (2%)), PU (duodenal ulcer (DU) 33 (75%), gastric ulcer (GU) 10 (23%), both PU and DU 1 (2%)). GSTT1 null genotype (GSTT1*0) was more common in patients with GN (30/76 (40%)) than in those with PU (5/44 (11%); p=0.001, odds ratio (OR) 5; 95% CI=1-4) and HC (23/100 (23%); p=0.02, OR 2; 95% CI=1-4). GSTT1*0 conferred a higher cancer risk for patients with DU (2/33 (6%), OR 10; 95% CI=2-45; p=0.00). GSTM1*0 and GSTP1 variant genotypes (ile/val and val/val) not alone but in combination with GSTT1*0 conferred a higher risk in PU patients (21 (28%) versus 5 (11%); OR 3; 95% CI=1-9; p=0.04). Both GSTM1*0 (16/26 (61%) versus 10/40 (25%); p=0.003, OR 5; 95% CI=2-14) and GSTT1*0 (12/26 (46%) versus 13/40 (33%); p=0.2, OR 2; 95% CI=0.6-5) were associated with a higher risk of diffuse tumor than of intestinal tumor.


CONCLUSIONS
GSTT1*0 alone and in combination with GSTM1*0 and GSTP1 variant genotypes is a risk factor for GN in the Indian population. Low GSTT1*0 in DU patients may play a protective role against GN. GSTM1*0 and GSTT1*0 are risk factors for diffuse GC.
Tripathi
Shweta
S
Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Ghoshal
Ujjala
U
Ghoshal
Uday C
UC
Mittal
Balraj
B
Krishnani
Narendra
N
Chourasia
Dipti
D
Agarwal
Ashok K
AK
Singh
Kartar
K
D004415:Dyspepsia / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000235:genetics*
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1