Abstract:
Background: Theglucose 6 ohosphate dehydrogenase (G6PD) enzyme is the first and rate-limiting enzyme in the oxidative arm of the Pentose Phosphate Pathway (PPP). People with G6PD deficiency are susceptible to hemolytic anemia, an X-linked recessive disorder. Moreover, the PPP is an important pathway in cancer as it supplies cancer cells with their high need for nucleic acid synthesis and the produced NADPH is important for the synthesis of fatty acids and to deal with oxidative stress. Therefore, in cancer cells were NADPH consumption is high, G6PD activity is also high. As such, G6PD deficient cells are not able to produce nucleic acids and to use NADPH for fatty acids synthesis leading to ROS accumulation leaving the cells vulnerable to oxidative and energetic stress. Here we intended to explore anemia related G6PD mutations and their possible protective role in cancer.
Materials and Methods: Anemia related G6PD mutations will be extracted and manually curated from published papers. Databases to use for curation will include the UCSC Genome Browser and ClinVar. Cancer related G6PD mutations and expressions will be extracted from The Cancer Genome Atlas (TCGA). Finally, the R programming language will be used for data analysis.
Results: We extracted and curated 151 G6PD mutations related to favism and anemia in the literature. In cancer, 150 G6PD mutations were identified in different cancer types with very low-frequency rates. In total, 20 mutations are common between both sets.
Conclusion: Our analysis will extend our knowledge of the protective role of G6PD deficiency against cancer.
