Common polymorphisms in GSTM1, GSTT1, GSTP1, GSTA1 and susceptibility to colorectal cancer in the Central European population.
BACKGROUND
Central Europe presents with the highest incidence of sporadic colorectal cancer (CRC) worldwide. As sporadic CRC represents a typical multifactorial disease, it is characterized by intense interaction of the genetic background with the environment. Glutathione S-transferases could act as attractive susceptibility genes for CRC, as they are directly involved in conjugation between glutathione and chemotherapeutics, environmental pollutants and a wide spectrum of xenobiotics.


METHODS
In this study, we investigated associations of polymorphisms in glutathione S-transferases (GSTs) genes, that is GSTA1, GSTT1, GSTM1 and GSTP1, with CRC in a total of 197 cases and 218 controls originating from the Czech Central European population. Polymorphisms were assessed by polymerase chain reaction/restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction.


RESULTS
None of investigated polymorphisms showed any associations with CRC, with the exception of GSTP1; where the heterozygote genotype Ile105Val was associated with decreased risk of CRC (P = 0.043).


CONCLUSIONS
The frequencies observed in our study are in accordance with those from other European Caucasian populations. Based on our studies, examined variability in GST genes is not a major determinant of CRC susceptibility in the Central European population.
Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Renata
R
Hezova
Julie
J
Bienertova-Vasku
Milana
M
Sachlova
Veronika
V
Brezkova
Anna
A
Vasku
Marek
M
Svoboda
Lenka
L
Radová
Igor
I
Kiss
Rostislav
R
Vyzula
Ondrej
O
Slaby
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D018153:Czech Republic / Q000453:epidemiology; D004198:Disease Susceptibility / Q000201:enzymology*; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D044465:White People / Q000235:genetics
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C484555:GSTA1 protein, human; C496556:GSTP1 protein, human