The GSTP1 Ile105Val Polymorphism is not Associated with Susceptibility to Colorectal Cancer

Abstract

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. 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. A member of the glutathione-S-transferase (GST) family, GSTP1, is an attractive candidate for involvement in susceptibility to carcinogen-associated colorectal cancer. An AgG transition in exon 5 resulting in an Ile105Val amino acid substitution has been identified which alters catalytic efficiency. The present study investigated the possible impact of Ile105Val GSTP1 polymorphism on susceptibility to colorectal cancer. in Jordan We examined 90 tissue samples previously diagnosed with colorectal carcinoma, and 56 non-cancerous colon tissues. DNA was extracted from paraffin embedded tissues and the status of the GSTP1 polymorphism was determined using a polymerase chain reaction restriction fragment length polymorphism (RFLP) method. No statistically significant differences were found between colorectal cancer cases and controls for the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes. The glutathione S-transferase polymorphism was not associated with risk in colorectal cancer cases in Jordan stratified by age, sex, site, grade or tumor stage. In conclusion, the GSTP1 Ile105Val polymorphism is unlikely to affect the risk of colorectal cancer.

Glutathione S Transferases: Biochemistry, Polymorphism and Role in Colorectal Carcinogenesis

“…Another study from Jordan by Khabaz MN [71] revealed no statistically significant differences between GSTP1 genotypes and CRC risk.…”

Review GST genes polymorphisms and the risk of colorectal cancer development

“…[15], and Khabaz [10]. These researchers concur that GSTP1 gene polymorphism does not exert any effect on the risk of contracting colorectal cancer.…”

“…These researchers concur that GSTP1 gene polymorphism does not exert any effect on the risk of contracting colorectal cancer. In the study by Khabaz, after analysing genotypes of 90 CRC tissue specimens and 56 specimens of healthy tissues of the large intestine, no statistically significant differences were observed between GSTP1 genotypes [10]. …”

Polymorphism of Selected Genes Coding for Xenobiotic-Metabolizing Enzymes and Susceptibility to Colorectal Cancer in a Saudi Population

“…In Saudi Arabia, few are the studies dealing with gene polymorphism and the susceptibility to CRC. No association could be detected between the susceptibility to CRC and resistin promoter C-180G genotype (Al-Harithy and Al-Ghafari, 2010), PARP-1 Val762Ala (Alshammari et al, 2014), GSTP1 Ile105Val (Khabaz, 2012) and autozygosity (Siraj et al, 2012). On the other hand, MMP-2C-qa306T ANP (Saeed et al, 2013 a), PARP1 Lys933Asn and Parp-1 Lys945Asn (Alshammari et al, 2014), rs 961253 Lys25Arg (Khan et al, 2014), CYP1A1, CYP2E1 and GSTM1 (Saeed et al, 2013b) were significantly associated withCRC.…”

“…According to the latest report of the National Cancer Registry (Al-Eid et al, 2011), CRC is the first most common cancer among Saudi males (12.9%) and the third among the Saudi females (9.4%), being the second most common malignancy among Saudis for all ages (10.3%). Sporadic CRC is a typical multifactorial disease, arising from environmental exposures (air pollution, dietary carcinogens, cigarette smoke), susceptibility genes and the interaction between genotypes and environments (Khabaz, 2012 andHezova et al, 2012)). Exposure to polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) have long been suspected to play a prominent role in CRC aetiology (Al-Saleh et al, 2008).…”