Polymorphisms in antioxidant defence genes and susceptibility to hepatocellular carcinoma in a Moroccan population

Abstract

Reactive oxygen species have been related to the aetiology of cancer as they are known to be mitogenic and therefore capable of tumour promotion. The aim of this study was to assess the role of common variation in three polymorphic genes (MnSOD Ala-9Val, GPX1 Pro198Leu and CAT -262 C > T) coding for antioxidant defence enzymes in modulating individual susceptibility to hepatocellular carcinoma (HCC) using a case-control study (cases = 96 and controls = 222). PCR-RFLP and sequencing methods were used to determine the genotype. Overall, there were no associations between genotypes GPX1 and HCC risk (OR, 1.16; 95% CI, 0.56-2.42; p = 0.685). The MnSOD Ala/Ala and CAT TT genotypes were more frequent in HCC than in control (p = 0.001 and p = 0.072, respectively). Further analyses stratified by gender or HCV infection revealed that men and HCV-infected patients carrying CAT TT genotype had a higher risk to develop HCC when compared with controls (OR = 15.94; 95% CI, 3.48-72.92; p < 0.000001 and 12.01; 95% CI, 0.64-223.63, p = 0.056, respectively). Combined MnSOD Ala/Ala and GPx1 Leu/Leu had a synergistic effect on HCC risk, with an OR of 3.84 (p = 0.029). Furthermore an even more pronounced risk was observed when we combined MnSOD Ala/Ala and CAT TT (OR = 13.60, p = 0.023). It appears that variants in MnSOD, CAT or GPX1 have an influence on HCC risk in this cohort. Furthermore, it is possible that cumulative defects in protection from oxidative stress may result in increased risk of liver cancer in the Moroccan population.

Biochemical and histological evidences for the antitumor potential of <i>Teucrium Oliverianum</i> and <i>Rhazya stricta</i> in chemically-induced hepatocellular carcinoma

“…Moreover, Reactive oxygen species have been related to the aetiology of cancer as they are known to be mitogenic and therefore capable of tumour promotion. Thus, it is possible that cumulative defects in protection from oxidative stress may result in increased risk of liver cancer in the Moroccan population (Ezzikouri et al, 2010). Treatment of the HCC group with R. stricta extract led to significant decrease in serum glypican 3 level while it produced insignificant decrease in serum golgi 73 level as compared to the untreated HCC group.…”

GPx-1 polymorphism (rs1050450) contributes to tumor susceptibility: evidence from meta-analysis

“…Thereafter, emerging studies have been done to evaluate the association between GPx-1 Pro198Leu polymorphism and risks for diVerent types of tumor in diverse populations, such as breast cancer (Ravn-Haren et al 2006;Cox et al 2004;Ahn et al 2005;Hu and Diamond 2003;Knight et al 2004;Cebrian et al 2006), lung cancer (Rosenberger et al 2008;Yang et al 2004;Ratnasinghe et al 2000;RaaschouNielsen et al 2007;Skuladottir et al 2005;Lee et al 2006), bladder cancer (Ichimura et al 2004;Paz-y-Mino et al 2010;Reszka et al 2009;Goerlitz et al 2011), prostate cancer (Choi et al 2007;Arsova-SaraWnovska et al 2009;Steinbrecher et al 2010), colorectal cancer Hansen et al 2005Hansen et al , 2009 and other cancers (Rajaraman et al 2008;Bhatti et al 2009;Wang et al 2008;Hu et al 2004;Ezzikouri et al 2010;Lightfoot et al 2006;Wu et al 2010;Tang et al 2010;Vogel et al 2004;He et al 2011). However, the results from those studies remain debatable rather than conclusive.…”

Epidemiology and Polymorphisms Related to Bladder Cancer in Ecuadorian Individuals

“…Possible modification of associations between genetic polymorphisms and bladder cancer risk was also achieved by stratifying cases based on old age (OR = 5.3; 95% CI 2.9-9.5; p<0.001), sex (OR = 0.6; 95% CI 0. Ezzikouri, et al, 2010;Hu, et al, 2010;Arsova-Sarafinovska, et al, 2009;Hansen, et al, 2009). The incidence of these polymorphisms according to the population analyzed, for example: the allelic frequency of L/L in the Japanese population is 0.05, and in the Caucasian population it is 0.36 (Ichimura, et al, 2004;Hu & Diamond, 2003).…”

“…Mutation in gene GPX1, which locates at chromosome 3p21, is one of the major factors regulating GPX1 activity. And among these, a genetic polymorphism at codon 198, resulting in either a proline (Pro) or leucine (Leu) at the corresponding position of the encoded peptide, have drawn increasing attention in the etiology of several cancers Ezzikouri, et al, 2010). In humans, the selenium-dependent activation of GPX 198Leu mutant enzyme is lower than for the GPX 198Pro wild-type enzyme (Hu, et al, 2010).…”