Relationship Between Glutathione S-transferase M1, T1 And P1 Polymorphisms And Prostate Cancer Risk In Chinese Population

Environmental carcinogens are metabolized in vivo by enzymatic reactions it can be activated or inactivated. Thus the genetic difference of the enzymatic system is believed to be one of the most important factors in determining susceptibility to cancer. Glutathione S-transferases (GSTs),a dimeride isoenzyem,one of the most important phrase II enzymes ,can induce substrates to conjugate with glutathione-S and most often creating a more water-soluble conjugate, which may be less toxic and more readily excretable. for most of the substrates are surrounding substances or oxidative stress products including environmental carcinogens ,GSTs play an important role in inducing carcinogen excreted, cytoprotective and anticancer action. Four GST isoenzyme classes have been identified by chromosomal localization and sequence homology -alpha, mu, pi and theta ,the posterior three subfamilies are more considerable .These enzymes take part in different enzymatic reactions, but the ranges of their substrates are partial overlapping . GST-mu,theta,pi is encoded by GSTM1,GSTT1 and GSTP1 respectively . hereditary differences in some GST enzyme activities are due to genetic polymorphisms. GSTM1 and GSTT1 enzyme activities is absent as a result of the inheritance of two null alleles (deletion of the gene). A coding sequence polymorphism (A313G, codon I105V) of GSTP1 has been documented which encodes for an enzyme with reduced catalytic activity for certain substrates and altered thermostability. GSTM1 and GSTP1 are responsible for the detoxification of carcinogenic polycyclic aromatic hydrocarbons, such as benzo(a)pyrene and the mycotoxin aflatoxin, while GSTT1 can detoxify smaller reactive hydrocarbons, such as ethylene oxide. GSTs may also have a role in the metabolism of lipid and DNA products of oxidative stress and play an important role in the course of drug resistance too. The GSTM1 null genotype has been associated with an increased risk of lung, bladder, breast and colon cancers . The GST1 null genotype has been found to increase the risk for developing colorectal cancer and myelodysplastic syndromes. An association has been found between the GSTP1 105 Val homozygosity and a risk of bladder cancer, testicular cancer and breast cancer. For the distributions of GSTs polymorphisms have substantial geographical and racial variation in incidence ,and the conclusion of the research are not conformity ,The aim of this study was to evaluate the frequencies of GSTM1, GSTP1 and GSTT1 gene types in Chongqing population and the relationship between the polymorphisms of them and the risk of prostate cancer following jobs were done in our research. 1. We collected blood samples from 81 prostate cancer patients and 90 controls with age above 50 in Chongqing , DNA was extracted from each blood sample . 2. the frequencies of GSTM1,GSTT1 genotypes were analyzed using polymerase chain reaction (PCR). 3. the frequencies of GSTP1 I105V genotypes were analyzed using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) . 4. linking with clinical statistics , the relationship between the polymorphisms of GSTM1, GSTP1 and GSTT1 and disease status and Gleason grade of prostate cancer was analyzed . results 1. Statistical difference was not found in the distribution of GSTM1(null) and GSTT1(null) in cases and controls. Neither the GSTM1null genotype nor the GSTT1 null genotype was associated with prostate-cancer risk, but the combined gene type ,GSTM1(null)-GSTT1(null)have significant relationship with prostate cancer risk. 2. Statistical difference was not found in the distribution of GSTP1-105Val /Val gene type, it has positive correlation with the risk of prostate cancer in Chinese population. 3. No statistically significant associations were found between polymorphism of GSTM1,GSTT1 or GSTP1 I105V with disease status and Gleason grade of prostate cancer.