Abstract

AimTo assess the association of GLO1 C332C gene polymorphism with breast cancer risk at different stages of the disease and to investigate the effect of this gene polymorphism on its mRNA expression and enzyme activity.MethodsGLO1 C332C gene polymorphism was analyzed by PCR-RFLP in 100 healthy controls and 200 patients with breast cancer (100 patients with stage I & II and 100 patients with stage III & IV). GLO1 mRNA expression was measured by real time PCR. Serum GLO1 enzyme activity was measured colorimetrically.ResultsGLO1 A allele was associated with increased risk of breast cancer [OR (95%CI)= 2.8(1.9-4.1), P < 0.001]. Its frequency was significantly higher among advanced stages of breast cancer compared with localized tumors (OR (95%CI)= 1.9(1.3-2.9), p < 0.001). GLO1 mRNA expression and enzyme activity were significantly higher in breast cancer patients compared to controls and they were much higher in the advanced stages of the disease (P < 0.001). Carriers of AA genotype showed higher GLO1 expression and enzyme activity compared with carriers of CC genotype.ConclusionGLO1 C332C SNP was associated with overexpression of GLO1 mRNA and higher enzyme activity in breast cancer patients suggesting its role in the development of breast cancer and its progression from localized to advanced.

Highlights

  • Breast cancer is the most common cause of cancer related mortality and represents the most frequent malignancy in women [1]

  • Increased risk of breast cancer was observed with the homozygous AA genotypes of GLO1 when compared with the CC genotype carriers [odds ratio (OR): 6.6(3.1-14), p < 0.001]

  • The frequency of GLO1 A allele was significantly higher in breast cancer patients compared to controls [OR: 2.8(1.9-4.1), p < 0.001]

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Summary

Introduction

Breast cancer is the most common cause of cancer related mortality and represents the most frequent malignancy in women [1]. The high prevalence of breast cancer provides a strong rationale for identifying new molecular targets that can be modulated. Oxidative stress might have important roles in breast cancer development and progression [2]. Gene polymorphisms of antioxidant and antiglycation enzymes might affect individual susceptibility to breast cancer [3]. The antioxidant systems against oxidative and carbonyl stresses include glyoxalase I (GLO1) [4]. GLO1 is responsible for the detoxification of Methylglyoxal (MG), a byproduct of glycolysis. GLO1 catalyzes the binding of MG to reduced glutathione forming S-lactoylglutathione [5].

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