Ile105Val GSTP1 polymorphism and susceptibility to colorectal carcinoma in Bulgarian population.
OBJECTIVE
Etiologically, the sporadic colorectal cancer (CRC) is a complex and multifactorial disease that is linked to both exogenic and endogenic factors. Accumulating evidence indicates that susceptibility to cancers, including CRC, is mediated by genetically determined differences in the effectiveness of detoxification of potential carcinogens. A member of the glutathione-S-transferase (GST) family, GSTP1, is an important candidate for involvement in susceptibility to carcinogen-associated CRC. An A-->G transition in exon 5 of the GSTP1 gene resulting in Ile(105)Val amino acid substitution has been identified. This change leads to alteration in catalytic efficiency of variant enzyme. The aim of the current study was to evaluate the influence of Ile(105)Val GSTP1 polymorphism on susceptibility to CRC.


METHODS
The GSTP1 genotyping was conducted in a case-control study of 80 ethnic Bulgarian CRC patients and 126 unaffected controls using polymerase chain reaction restriction fragment length polymorphism method.


RESULTS
A statistically significant case-control difference in genotype frequencies was observed: 0.69 vs 0.54 for Ile/Ile, 0.22 vs 0.39 for Ile/Val, and 0.09 vs 0.07 for Val/Val (p = 0.049). The odds ratio (OR) for Val/Val was close to 1 (0.96, 95%CI: 0.35-2.66, p = 0.942), whereas the OR for Ile/Val was significantly lower, 0.45 (95%CI: 0.24-0.86, p = 0.016), compared to the referent Ile/Ile genotype. Although a prevalence of the GSTP1 variant allele-containing genotypes (Ile/Val or Val/Val) was found in controls than in patients (OR = 0.53, 95%CI: 0.30-0.96, p = 0.035), the allele frequencies did not show significant difference between cases and controls (p = 0.127).


CONCLUSIONS
Based on the obtained protective effect of Ile/Val GSTP1 genotype, we could suggest that Ile(105)Val GSTP1 polymorphism may play some role in susceptibility to CRC.
Vlaykova
Tatyana
T
Department of Chemistry and Biochemistry, Medical Faculty, Trakia University, Stara Zagora, Bulgaria. tvlaykov@mf.uni-sz.bg
Miteva
Lyuba
L
Gulubova
Maya
M
Stanilova
Spaska
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002031:Bulgaria; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi