Breast cancer and DDT: putative interactions, associated gene alterations, and molecular pathways

The global burden of cancer has recorded an ever-increasing trend in the developing world. The GLOBOCAN, 2018 report has ranked breast cancer (BC) as the second (11.6%) most common form of cancer afflicting the female population worldwide. BC presents as a multi-factorial trait with numerous risk factors associated with the disease phenotype. Besides, genetic predisposition, exposure to environmental chemicals, and pollutants are considered to increase the magnitude of disease in susceptible individuals. Hence, the present observational study aims to investigate those proteins in the host which interact with the persistent organic pollutant, 2,4-dichlorodiphenyltrichloroethane (DDT), and associated alterations in genes encoding these proteins using a computational approach. The genetic alterations were ascertained using the Breast Invasive Carcinoma dataset available in the cBioportal database. The possible functional consequences of mutations identified in the selected dataset were further assessed using tools such as I-Mutant and PROVEAN. The ERBB2 (14%) and FASLG (10%) genes were found to harbor the highest frequency of gene alterations. Gene amplification and deep deletions were the most commonly observed alteration in almost all the genes investigated. Additionally, several synonymous, non-synonymous, frameshift, splice site mutations were also documented. The gnomAD analysis revealed three polymorphic variants in HTR2A (rs539430264), ESR2 (rs905821436), and CYP2B6 (rs757834610), all of which had a minor allele frequency < 0.01. Population-wide screening of observed gene alterations can provide clues on the putative association of these gross and single nucleotide substitutions with the pathophysiology and progression of breast cancer. Experimental genotyping and functional analysis of mutations is warranted to further prove the adverse effects of organochlorine compounds on female health.