Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of prostate cancer in Algerian population

Abstract

Background Prostate cancer is the most common cancer in the world, and its etiology involves the interaction of genetic and environmental factors. Interindividual differences observed in the metabolism of xenobiotics may be due to polymorphisms of genes encoding the detoxification enzymes. This genetic variability seems to be associated with differences in susceptibility to certain types of cancers, including prostate cancer. Our study has been made in order to investigate a possible genetic predisposition to prostate cancer in an Algerian population, through the analysis of genetic polymorphisms of three enzymes metabolizing xenobiotics namely cytochrome P450 (CYP) 1A1, glutathione S-transferase mu 1 (GSTM1) and GST theta 1 (GSTT1). Methods The current case–control study included 101 prostate cancer patients and 101 healthy controls. Genotyping of CYP1A1 T3801C polymorphisms and GSTM1/GSTT-null was made, respectively, by PCR-RFLP and multiplex PCR. Results No significantly positive associations were found for the CYP1A1 T3801C [p = 0.71, OR = 1.23 (0.56–2.72)] and GSTM1-null [p = 0.26, OR = 1.37 (0.76–2.4)] polymorphisms and prostate cancer susceptibility. However, we detect a highly significant association between GSTT1-null genotype [p = 0.03, OR = 2.03 (1.06–3.99)], GSTM1/GSTT1-double null genotype [p = 0.027, OR = 2.6; CI (1.07–6.5)] and prostate cancer risk. Furthermore, no statistically significant differences between the studied polymorphisms and tumor parameters (the Gleason score and clinical stages of aggressiveness) at diagnosis of PCa. Conclusions The risk of developing prostate cancer in Algeria does not appear to be associated with CYP1A1 T3801C genotypes and GSTM1-null, but GSTT1-null and GSTM1/GSTT1-double null genotypes increased the risk of prostate cancer.

Molecular detection of GSTM1 and GSTT1 gene polymorphisms and their association with prostate cancer risk

“…But for the genotype (GSTM1 -, GSTT1 -) it appeared in 43 (86.0%) people of the patients group and 40 (80.0%) people of the healthy group, while the genotype (GSTM1 + and GSTT1 + ) was present in 7 (14.0%) people Of the group of patients and 10 (20.0%) individuals of the healthy group, the results of the statistical analysis did not prove any significant association between the two genotypes (GSTM1 --GSTT1and GSTM1 + -GSTT1 + ) with the two groups of patients and healthy individuals. The results of the current study agreed with the results of the study (Zhang et al, 2019;Medjani et al, 2020b( in the absence of an association between prostate cancer and the GSTM1 gene for both GSTM1 + and GSTM1and the study also agreed with our study regarding the existence of an association between prostate cancer with the GSTT1 gene and its genetic (GSTT1 + , GSTT1 -) for both healthy and patient groups.…”