Some studies, which combined data from
other genotypes, have shown that the concurrent lack of GSTM1/GSTT1 and GSTP1 genes posed a significantly increased risk of prostate cancer [20, 28, 29]. However, these studies have not been confirmed by other authors [23]. One of the reasons for such discrepancy in the findings might lie in the difficulty of analyzing the impact of the modified GST activity on detoxification of known carcinogens. GST has overlapping substrate specificities; therefore, deficiency of a single GST isoenzyme may be compensated by other isoforms. Another important factor is the differential expression of genes for GST in different cells. The variation in published prostate cancer prevalence rates can be attributed partly to methodological differences in survey design, including age distribution of the population surveyed. It is also known that the incidence of prostate cancer is underestimated, www.selleckchem.com/products/AZD7762.html maybe due to poor compliance of elderly with screening recommendations. Thus, regular follow-ups are difficult
to achieve and, as a consequence, many men never know they have prostate cancer. It has been reported that the calculated prevalence of prostate cancer at death (i.e. histological evidence) for a 60-year-old man is 32%, whereas but the prevalence in living men (clinically-defined disease) is approximately 4% [30]. In contrast to the possible role of GST in environmental carcinogenesis, Masitinib (AB1010) it has SN-38 been suggested that GST genotypes conferring lower enzyme activity may be of advantage for the patients who are undergoing chemotherapeutic treatment for neoplastic disease because reduced detoxification potentially enhances effectiveness of cytotoxic drugs [31]. Although somewhat speculative, the GST polymorphisms might be a protective factor during the
period of chemotherapy, as the carriers of GST null genotypes might better respond to the treatment. At present, it is difficult to confidently evaluate the GST polymorphisms impact on prostate cancer patients. Apparently, it would be far too simplistic to attribute a complex problem such as prostate cancer to any single cause. Although it is methodologically difficult to identify and separate all the factors that make it difficult to identify individual changes, it is nevertheless possible to conduct a carefully designed international and/or multicentric study, or of combining results of several independent studies on the topic. Conclusion Our results suggest a possible association between the GSTP1 Val/Val genotype and the occurrence of prostate cancer. However, broad confidence intervals indicate a naturally high variability in GST polymorphisms in the population, which has given less weight to the observed differences in GSTP1 Val/Val genotype frequencies between the patients and the control subjects.