The glutathione S transferase (GST) family is a major part of cellular defense mechanisms against endogenous and exogenous substances, many of which have carcinogenic potential. The GSTP1 gene is a member of the glutathione S-transferases (GSTs) family of proteins; it encodes a phase II metabolic enzyme that detoxifies reactive electrophilic intermediates. GSTP1 is expressed in normal tissues at variable levels in different cell types. It is frequently over-expressed in many human cancers and the expression increases with tumor progression and is associated with a more aggressive biology, poor patient survival, and resistance to therapy.
The GSTP1 gene spans approximately 3 kb and is located on chromosome 11q13.2 and contains seven coding exons. To date, two polymorphisms in the coding DNA sequence of the GSTP1 gene have been identified; an A>G transition at nucleotide 313 in exon 5, resulting in a Ile105Val, and a C>T transition at nucleotide 341 in exon 6, resulting in replacement Ala114Val.
Alteration in the expression level or structure of the glutathione-S-transferase (GST) enzymes may lead to inadequate detoxification of potential carcinogens and consequently contribute to cancer development.
Khabaz (2012) investigated the possible impact of Ile105Val GSTP1 polymorphism on susceptibility to colorectal cancer in Jordan. Ninety tissue samples previously diagnosed with colorectal carcinoma, and 56 non-cancerous colon tissues were analyzed. No statistically significant differences were found between colorectal cancer cases and controls for the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes. Khabaz (2012) concluded that the GSTP1 Ile105Val polymorphism was not associated with risk in colorectal cancer cases in Jordan stratified by age, sex, site, grade or tumor stage. In a subsequent study, Khabaz et al. (2014) investigated the GSTP1 polymorphism in 100-tissue samples previously diagnosed as breast carcinoma, and in 48 non-cancer age-matched breast tissues. Among breast cancer cases, 58%, 40%, and 2% were homozygous (Ile/Ile), heterozygous (Ile/Val), and homozygous (Val/Val), respectively. In the control group, 58%, 38%, and 4% were homozygous (Ile/Ile), heterozygous (Ile/Val), and homozygous (Val/Val), respectively. Khabaz et al. (2014) excluded a possible involvement of the GSTP1 gene polymorphism in susceptibility to breast carcinoma in the North Jordanian female population.
[See also: Saudi Arabia > Bu et al., 2004].
[See: Saudi Arabia > Bu et al., 2004].