Glutathione S-transferases mu 1, theta 1, pi 1, alpha 1 and mu 3 genetic polymorphisms and the risk of colorectal and gastric cancers in humans.
BACKGROUND
Glutathione S-transferases (GSTs) are considered to be cancer susceptibility genes as they play a role in the detoxification of carcinogenic species. This study aimed to elucidate the influence of several GST polymorphisms on colorectal and gastric cancer risk.


METHODS
GST mu1 (GSTM1), theta1 (GSTT1), pi1 (GSTP1), alpha1 (GSTA1) and mu3 (GSTM3) genotypes were determined in 144 colorectal cancer patients, 98 gastric cancer patients and 329 healthy control individuals.


RESULTS
Colorectal cancer: the risk is greater for carriers of the GSTM1 null genotype (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.25-2.91), for carriers of the GSTT1 null genotype (OR = 3.62, 95% CI = 2.34-5.62), and for simultaneous carriers of both GSTM1 and GSTT1 null genotypes (OR = 4.98, 95% CI = 2.77-9.00). Carriers of the GSTP1 104 Val/Val genotype are at a lower risk (OR = 0.31, 95% CI = 0.09-0.88). Among carriers of the GSTP1 Ile/Ile genotype, smoking increases the risk compared with nonsmoking (OR = 2.35, 95% CI = 1.11-4.99). Gastric cancer: the risk is greater for carriers of the GSTT1 null genotype (OR = 2.58, 95% CI = 1.53-4.36) and for simultaneous carriers of both GSTM1 and GSTT1 null genotypes (OR = 3.32, 95% CI = 1.62-6.77). Carriers of the GSTP1 104 Val/Val genotype are at a lower risk (OR = 0.20, 95% CI = 0.02-0.86).


CONCLUSIONS
The GSTT1 null genotype, particularly if it is associated with the GSTM1 null genotype, greatly increases the risk for colorectal and gastric cancers. The GSTP1 104 Val/Val genotype may protect from both malignant tumors.


CONCLUSIONS
This study indicates that GST polymorphisms, in particular the GSTM1/GSTT1 double-null haplotype, can be considered low-penetrance genes for gastrointestinal cancer.
Martínez
Carmen
C
Department of Pharmacology and Psychiatry, University of Extremadura, Badajoz, Spain.
Martín
Felipe
F
Fernández
Juana M
JM
García-Martín
Elena
E
Sastre
Javier
J
Díaz-Rubio
Manuel
M
Agúndez
José Ag
JA
Ladero
José M
JM
D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics*
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C484555:GSTA1 protein, human; C483009:GSTM3 protein, human