An association between glutathione S-transferase gene polymorphism and prostate cancer in the Slovak population

Konference: 2006 2. ročník Dny diagnostické, prediktivní a experimentální onkologie

Kategorie: Genitourinární nádory

Téma: Postery

Číslo abstraktu: 024p

Autoři: M. Sivoňová; RNDr. Tatiana Matáková, Ph.D.; Prof. MUDr. Dušan Dobrota, CSc.; RNDr. Jozef Hatok, Ph.D.; M. Franeková; MUDr. Ján Kliment jr., PhD.

In the metabolism of numerous potential carcinogens are involved biotransformation enzymes, glutathione S-transferases (GSTs). There is evidence that suggests that detoxification enzymes may play a role in the formation of prostate cancer. GSTP1 has a polymorphic site at codon 105 (exon 5), where an adenosine-to-guanosine (A-G) transition causes an Ile-to-Val substitution (Ile105Val) and produces a variant enzyme with lower activity and less capability of effective detoxification. The GSTM1 and GSTT1 genes exhibit null (i.e., deletion) polymorphisms; in specific individuals, homozygous deletion (i. e., both copies lost) of these genes can be detected. In the present study, we investigated the association of GSTP1, GSTM1 and GSTT1 polymorphisms with susceptibility to prostate cancer in the Slovak population. Genotypes of blood specimen DNA were determined for 92 men with incident cases of prostate cancer and for 153 control subjects by age 50. Genomic DNA and the polymerase chain reaction were used to determine the GSTP1, GSTM1 and GSTT1 genotypes in the study subjects. Associations between specific genotypes and development of prostate cancer were examined by use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). For GSTP1, the data were suggestive of a trend of increasing risk with higher numbers of codon 105 valine alleles compared with isoleucine alleles, a 2.15-fold increased risk of prostate cancer (95 % CI = 0.384–12.09) was associated with Val/Val homozygosity. There was no significant link between Ile/Val genotype and risk of prostate cancer (OR 1.0; 95%CI=0.469–2.13). The frequencies of GSTT1 null genotype did not differ between patients and controls (OR 1.2; 95% CI = 0.606–2.22). The overall frequency of GSTM1 null was lower in cases as compared with controls (OR–0.8; 95 % CI = 0.473–1.34).
Our findings suggested that GSTP1 Val/Val genotype may be associated with an increased susceptibility to prostate cancer in the Slovak population. Further, both GSTM1 null and GSTT1 null genotypes did not appear to influence the susceptibility to prostate cancer.
This work was supported by grants UK/264/2006, MVTS Bil/ČR/SR/UK/06 and AV 4/0013/05.

Datum přednesení příspěvku: 7. 12. 2006