Association of manganese superoxide dismutase gene polymorphism (Ala-9Val) and breast cancer in males and females

Abstract

Introduction: One of the several metabolic pathways involved in breast carcinogenesis is the human polymorphism in the mitochondrial targeting sequence Ala-9Val of the manganese superoxide dismutase (MnSOD) gene, which has been previously associated with increased risk of breast cancer in females. Since there is no previous report on this polymorphism in male breast cancer, the objective of this study is to analyze MnSOD polymorphism in a population of males and females with breast cancer from the southernmost state of Brazil, compared to healthy controls. Methods: A case-control study of one hundred patients affected by breast cancer (11 men and 89 women) and 370 healthy age-adjusted database controls was performed. DNA was extracted from paraffin-embedded tumoral tissue. MnSOD polymorphism was determined by PCR-RFLP techniques using restriction enzyme Hae III. Chi-square test was used to compare MnSOD frequency distribution. Results: MnSOD genotypic frequencies in all patients with breast cancer were AA = 15%; AV = 56%; VV = 29% and controls AA = 6.5%; AV = 68.1% and VV = 25.4%. Both male and female patients with breast cancer presented significantly higher AA frequencies compared to controls (p = 0.035), suggesting strong association of this genotype with breast cancer. A 2.15-fold (95% confidence interval [CI] 1.393-4.541) risk of breast cancer was found among individuals carrying the MnSOD AA allele-containing genotypes compared with the MnSOD VV and AV genotypes. Discussion: These results confirm the already established association of MnSOD AA genotype with female breast cancer and further indicate a similar frequency distribution and increased risk in the male population.

Ginger and Onion: New and Novel Considerations

“…Ginger was reported to suppress TPA-induced oxidative stress in human promyelocytic leukemia [29]. In some research works it have been proved that ginger compounds effectively inhibit superoxide production [30]. Several reports indicate that ginger suppresses lipid peroxidation and protects the levels of reduced glutathione [31].Ginger was reported to decrease age-related oxidative stress markers and was suggested to guard against ethanol-induced hepatotoxicity by suppressing oxidative consequences in rats treated with ethanol [32].…”

Association between Gene Polymorphism of Manganese Superoxide Dismutase and Prostate Cancer Risk

“…Moreover, Woodson et al [25] and Kang et al [26] found that the Ala allele was associated with an increased risk of PCa, whereas the Val allele was related with an increased risk of lung cancer [27] and of bladder cancer [28]. However, other studies showed different results, probably because of gene-gene, geneenvironmental, and physiological interactions associated with MnSOD polymorphism and cancer [6].…”

“…Manganese superoxide dismutase (MnSOD) is the most effective antioxidant enzyme in mitochondria and has an important role in protecting cells from reactive oxygen species (ROS)–induced oxidative damage . It has been suggested that MnSOD (Ala‐9Val) gene polymorphism may alter the secondary structure of the protein and affects transport of MnSOD enzyme into the mitochondria .…”

Estudio de la asociación entre el polimorfismo Ala16Val de la enzima superóxido dismutasa dependiente de manganeso, la obesidad, y marcadores bioquímicos oxidativos e inflamatorios = Study of the association between the polymorphism Ala16Val of the enzyme manganesedependent superoxide dismutase, obesity and oxidative and inflammatory biochemical markers

“…208 Por otra parte, la investigación también sugiere que el genotipo VV, que presenta una menor eficiencia de la enzima SOD2, está relacionado con la disfunción endotelial e indicadores bioquímicos asociados con el riesgo cardiometabólico, como es el caso de las LDL oxidadas, y también interactúa con la hipercolesterolemia aumentando la tasa de peroxidación de lípidos y disminuyendo los niveles de enzimas antioxidantes como la propia SOD. 209 Las investigaciones realizadas por el equipo de investigación relacionado con la ejecución del presente estudio han encontrado una asociación entre el genotipo/alelo y el cáncer de mama en mujeres y hombres 210,211 , el cáncer de próstata y la inmunosenescencia 212 , mientras que otros estudios, también llevados a cabo por nuestro equipo de investigación, han encontrado una asociación entre el genotipo VV/alelo V y altas concentraciones de LDL oxidado, especialmente en pacientes mayores con diabetes tipo II 213 e hipercolesterolemia 214 , y sorprendentemente con mayor agresividad tumoral en aumento (mayor probabilidad de afectación ganglionar en el cáncer de mama). 215 Con base a estos resultados se desplegaron también en las investigaciones in vitro mediante la construcción de líneas de linfocitos primarios y secundarios derivados de los individuos sanos (1) ¿Está la obesidad asociada a un estado inflamatorio de bajo grado?…”