GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high-risk italian population.
Glutathione S-Transferases (GSTs) are a family of phase II enzymes involved in the detoxification of potential carcinogens and provided of a strong antioxidant function by neutralizing electrophiles and free radicals. The GSTM1 and GSTT1 isoenzymes exhibit deletion polymorphisms, resulting in a lack of activity, and the null genotypes have been associated with increased cancer risk at several sites, including the stomach, although with contrasting results. We carried out a case-control study to evaluate whether these polymorphisms modulate the risk of developing gastric cancer (GC). Genotypes for GSTM1 and GSTT1 were obtained from a series of 175 histologically confirmed GC patients and a large series of 546 healthy controls randomly sampled from the general population of Tuscany, an area at high GC risk. No difference in the frequency of GSTM1 null genotype was observed between cases and controls, whereas the GSTT1 null genotype was more frequent among cases (p = 0.04). Multivariate single-gene analyses adjusted for possible confounders showed that the GSTT1 null genotype, but not the GSTM1 null genotype, was associated with an increased GC risk. Combined-genotype analyses showed a significantly increased GC risk only for the double null (GSTM1-GSTT1) genotype (OR = 2.27; 95% CI: 1.14-4.53). A statistically significant positive interaction between the 2 null genotypes was observed (p = 0.02). Our findings suggest that only subjects lacking both GSTM1 and GSTT1 activity are at increased GC risk. This study provides further support to the hypothesis that the risk of developing GC is influenced by inter-individual variation in both carcinogen detoxification and antioxidant capacity. (c) 2005 Wiley-Liss, Inc.
Palli
Domenico
D
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Center (CSPO), Scientific Institute of Tuscany, Florence, Italy. d.palli@cspo.it
Saieva
Calogero
C
Gemma
Simonetta
S
Masala
Giovanna
G
Gomez-Miguel
Maria Jesus
MJ
Luzzi
Ida
I
D'Errico
Mariarosaria
M
Matullo
Giuseppe
G
Ozzola
Giulio
G
Manetti
Roberto
R
Nesi
Gabriella
G
Sera
Francesco
F
Zanna
Ines
I
Dogliotti
Eugenia
E
Testai
Emanuela
E
D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D016481:Helicobacter Infections / Q000175:diagnosis; D016480:Helicobacter pylori / Q000302:isolation & purification; D006720:Homozygote; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1