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

• Published in: Free radical research Vol. 44; no. 2; pp. 208 - 216
• Main Authors: Ezzikouri, Sayeh, Feydi, Abdellah Essaid El, Afifi, Rajae, Benazzouz, Mustapha, Hassar, Mohammed, Pineau, Pascal, Benjelloun, Soumaya
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS) 2010; Taylor & Francis
• Subjects: Antioxidants; Antioxidants - metabolism; Cancer; Carcinoma, Hepatocellular; Carcinoma, Hepatocellular - etiology; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Case-Control Studies; Catalase; Catalase - genetics; Catalase - metabolism; Female; Genetics; Genotype; Glutathione Peroxidase; Glutathione Peroxidase - genetics; Glutathione Peroxidase - metabolism; Hepatocellular carcinoma; Human genetics; Human health and pathology; Humans; Hépatology and Gastroenterology; Life Sciences; Liver Neoplasms; Liver Neoplasms - etiology; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Male; Middle Aged; Morocco; oxidative response; polymorphism; Polymorphism, Genetic; Reactive Oxygen Species; Reactive Oxygen Species - metabolism; Superoxide Dismutase; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Morocco
• ISSN: 1071-5762; 1029-2470
• DOI: 10.3109/10715760903402906

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.