Association Between the PIK3CA Ile391Met Polymorphism and the Risk of Breast Cancer in an Iranian Population
IntroductionBreast cancer, as a multifactorial disease is the most frequent cancer among women and second most commonly diagnosed cancer in worldwide. Breast cancer is associated with mutations in several genes such as PIK3CA. Phosphoinositide 3 kinase (PI3K) is an important group of lipid kinases that regulate the vital cellular functions such as survival, proliferation, cell growth, motility, differentiation, and intracellular trafficking. The aim of this study is to evaluate the association of rs2230461 of PIK3CA gene with the incidence of breast cancer.
Materials and MethodsA total of 198 healthy donors and 205 breast cancer patients were recruited. Genomic DNA was extracted from peripheral blood leukocytes by Triton X100 technique. Genotyping was performed using RFLP-PCR protocol. Chi-square test, odds ratios (ORs) and 95% CIs were used to determine associations.
ResultsThere were no significant differences observed regarding the PIK3CA genotype frequencies at codon 391 between patient and control groups (P = 0.17). However, by comparing stage III breast cancer patients and control groups, there was a significantly higher frequency of the GG genotype among stage III cases compared to control (P = 0.01). Although the PIK3CA I391M polymorphism has been located in the C2 domain and doesn’t involve in the binding site, it can affect the protein function.
ConclusionsSince even those mutations that are far from the binding site can affect the protein function and change its dynamic behavior through allosteric impacts and lead to tumorigenesis at last. Since PIK3CA mutations mainly appear late in tumorigenesis, exactly before or coincident with invasion, and may be involved in tumor formation, it is suggested that this polymorphism may be involved in breast cancer invasion.
Journal of Applied Biotechnology Reports, Volume:5 Issue:1, 2018
8 - 12
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