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