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Breast cancer risk associated mitochondrial NADH-dehydrogenase subunit-3 (ND3) polymorphisms (G10398A and T10400C) in Bangladeshi women

Abstract

A D A Shahinuzzaman, Atiqur Rahman, Rokeya Begum, Gazi Nurun Nahar Sultana, M Manjurul Karim and Rowsan Ara Begum

Somatic mitochondrial DNA (mtDNA) mutations have been reported in many types of cancer cells, but very few reports document the prevalence of inherited mtDNA polymorphisms including NADHdehydrogenase (ND3) subunit polymorphisms in cancer patients compared to healthy control populations. Although, few mitochondrial ND3 subunit polymorphisms were reported in different cancers e.g. breast, esophageal cancer but the effect of polymorphisms on cellular metabolism and growth remain obscure. ND3 subunit with other ND subunits of Complex I and Cytochrome b of complex III of mtDNA Electron Transport Chain (ETC) are the major source of reactive oxygen species (ROS) as a toxic by-product of mitochondrial Oxidative Phosphorylation (OXPHOS), thus polymorphisms in these subunits has been proposed to cause an increased rate of ROS production, therefore, may contribute in developing cancer. In an attempt to investigate mtDNA polymorphisms associated with breast cancer risk, mtDNA from twenty four breast cancer patients and twenty healthy female individuals were studied. We report that two polymorphisms G10398A and T10400C are prevalent in 75% of breast cancer patients, compared to only 35% in healthy female individuals and the difference is statistically significant (P = 0.0138). It is therefore reasonable to assume that G10398A and T10400C single nucleotide polymorphisms may constitute an inherited risk factor for the development of breast cancer in Bangladesh.

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