GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: A comprehensive meta-analysis

Glutathione-S-Transferases in Development, Progression and Therapy of Colorectal Cancer

“…Our findings are analogous to the one of meta-analyses performed on a large number of published case-control studies. The results of these meta-analyses support the suggestion that GSTM1 and GSTT1 null polymorphisms are associated with increased risk of CRC, especially in the Caucasian population (Economopoulos &Sergentanis, 2010;Gao et al, 2010). Economopoulos et al have summarized the results from 44 studies for GSTM1 and 34 for GSTT1 null polymorphisms and concluded that GSTM1 null genotype carriers exhibited increased colorectal cancer risk in Caucasian population (OR=1.15, 95% CI: 1.06-1.25), but not in Chinese subjects (OR=1.03, 95% CI: 0.90-1.16).…”

“…Economopoulos et al have summarized the results from 44 studies for GSTM1 and 34 for GSTT1 null polymorphisms and concluded that GSTM1 null genotype carriers exhibited increased colorectal cancer risk in Caucasian population (OR=1.15, 95% CI: 1.06-1.25), but not in Chinese subjects (OR=1.03, 95% CI: 0.90-1.16). They reported similar results for GSTT1 null polymorphism: OR=1.31, 95% CI:1.12-1.54 for Caucasian population and OR=1.07, 95% CI:0.79-1.45 for Chinese subjects (Economopoulos &Sergentanis, 2010). Gao at al., carried out a meta-analysis of GSTM1 genotype data from 36 studied including 9149 patients with CRC and 13 916 control individuals (Gao et al, 2010).…”

“…In this regard a number of epidemiological studies have investigated the association of GSTM1 and GSTT1 genetic polymorphisms with colorectal cancer risk, however the results from these studies have also been with quite controversial conclusions (Cotton et al, 2000;Economopoulos &Sergentanis, 2010;Gao et al, 2010). The preliminary results from our study including very limited number of patients and controls (45 and 42), showed a statistically significant case-control difference in the presence of GSTT1 null genotype (0.30 vs. 0.07, p=0.006), and only a tendency for prevalence of GSTM1 null genotype in CRC patient (0.57 vs. 0.36, p=0.052) .…”

“…This genotype may provide enzyme with an adequate detoxification of some and relatively weak activation of other carcinogens, depending on their characteristics. Two recent large meta-analyses summarized the results focused on the role of GSTP1 Ile 105 Val from 16 published case-control studies involving a total of 4386 colorectal cancer patients and 7127 controls (Gao et al, 2009) and 19 studies with altogether 5421 cases and 7671 controls (Economopoulos &Sergentanis, 2010) .The results of the meta-analysis performed by Gao et al (Gao et al, 2009) sowed no strong evidence that the 105Val allele conferred increased susceptibility to colorectal cancer compared to 105Ile allele either in the whole pooled case-controls groups or in the stratified one: by race -Caucasian and Asian descent; by the type of controls -in healthy and hospital controls. They also did not find evidence for an association with colorectal cancer in dominant (OR= 1.02, 95% CI:0.94, 1.10) and co-dominant (OR= 0.88 , 95% CI: 0.77, 1.01) models for the effect of Val.…”

“…In addition to carcinogens and reactive oxygen species, the majority of anticancer drugs applied in the chemotherapy are also substrates and are biotransformed by xenobiotic-metabolizing enzymes, leading to their activation and/or detoxification (O'Brien &Tew, 1996;Eaton &Bammler, 1999;Townsend &Tew, 2003;Hayes et al, 2005;Michael &Doherty, 2005;Townsend et al, 2005). In this respect, great efforts have been focused to clarify the effects of genetic variations, expression and activity of xenobiotic-metabolizing enzymes in development, progression and therapy of cancers with different histological origin, including CRC (Ranganathan &Tew, 1991;Welfare et al, 1999;Cotton et al, 2000;de Jong et al, 2002;Dogru-Abbasoglu et al, 2002;Stoehlmacher et al, 2002;Ates et al, 2005;Romero et al, 2006;Liao et al, 2007;Pistorius et al, 2007;Koutros et al, 2009;Di Pietro et al, 2010;Economopoulos & Sergentanis, 2010).…”