Positive correlation between single or combined genotypes of CYP1A1 and GSTM1 in relation to prostate cancer in Chilean people.
BACKGROUND
The prostate cancer is a slowly progressing disease that begins decades prior to diagnosis. It has been suggested that there might be differences in susceptibility due to genetic polymorphisms in biotransformation enzyme genes. In the present work, associations between CYP1A1(Msp1), GSTM1(-/-) polymorphisms, and prostate cancer were analyzed in a case-control study.


METHODS
Genomic DNA was isolated from peripheral blood samples, collected on EDTA. PCR-RFLP was used to determine simultaneously Msp1 and GSTM1(-/-) polymorphisms.


RESULTS
In cancer patients, frequency of m2 variant allele (0.377) and GSTM1(-/-) (0.362) showed statistically significant increases compared to the control group (0.262 and 0.227, respectively). The estimate relative risks (OR) were higher for individuals carrying combined CYP1A1 and GSTM1 rare genotypes, in relation to individuals carrying CYP1A1 or GSTM1 alone. Multivariate logistic regression analysis including confounding factors (age, digital examination, and PSA antigen) showed even higher risk for individuals carrying m2m2 genotype (OR = 3.99; 95% CI, 1.27-12.54), GST(-/-) genotype (OR = 2.75; 95% CI, 1.31-5.79), and m2m2/GST(-) genotype (OR = 16.63; 95% CI, 1.67-165.48).


CONCLUSIONS
Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms are more susceptible to prostate cancer.
Acevedo
Cristian
C
Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Programe of Molecular and Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
Opazo
Jose Luis
JL
Huidobro
Christian
C
Cabezas
Juan
J
Iturrieta
Jeannette
J
Quiñones Sepúlveda
Luis
L
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002677:Chile; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011471:Prostatic Neoplasms / Q000235:genetics*
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase