Genetic polymorphism of glutathione S-transferase genes (GSTM1, GSTT1 and GSTP1) and susceptibility to prostate cancer in Northern India.
OBJECTIVE
To examine the association of glutathione-S-transferase (GST) gene polymorphisms in patients with sporadic prostate cancer, in a North Indian population, as GSTs are active in detoxifying a wide variety of endogenous or exogenous carcinogens, and genetic polymorphisms of GSTM1, GSTT1 and GSTP1 have been assessed to evaluate the relative risk of various cancers.


METHODS
We assessed 127 patients with prostate cancer and 144 age-matched controls, all from North India. The GSTT1 and GSTM1 null genotypes were identified by multiplex polymerase chain reaction (PCR) in peripheral blood DNA samples, and GSTP1-313 A/G polymorphism was determined by PCR/restriction fragment length polymorphism.


RESULTS
There was a significant association in null alleles of the GSTM1 (odds ratio 2.239, 95% confidence interval 1.37-3.65, P = 0.001) and GSTT1 (1.891, 1.089-3.282, P = 0.026) with prostate cancer risk, and in the -313 G alleles (Val) of the GSTP1 gene (2.48, 1.51-4.08, P < 0.001). The combined analysis of these three genotypes showed a further increase in the risks of prostate cancer (7.23, 2.42-22.6, P < 0.001).


CONCLUSIONS
The GSTP1-313 G polymorphism, and null alleles of GSTM1 and GSTT1, are strong predisposing risk factors for sporadic prostate cancer in North India.
Srivastava
Daya Shankar Lal
DS
Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow-226 014, Uttar Pradesh, India.
Mandhani
Anil
A
Mittal
Balraj
B
Mittal
Rama Devi
RD
D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human