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

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Abstract

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.

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Acknowledgments

The authors thank all the consorts and groups who were involved in the compilation of data from patients for public use. Our sincere thanks to all the patients who have indirectly contributed to the scientific community by providing consent for sharing their data for research use.

Funding

This work was supported by the Science and Engineering Research Board (SERB), Government of India (CRG/2019/003756 and EEQ/ 2019/000411).

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Authors and Affiliations

  1. Biomedical Research Unit and Laboratory Animal Centre - Dental Research Cell, Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Sciences [SIMATS], Saveetha University, Poonamallee High Road, Chennai, Tamilnadu, 600 077, India

    Vijayashree Priyadharsini Jayaseelan & Paramasivam Arumugam

  2. Department of Medical Oncology, Saveetha Medical College & Hospital, Saveetha Institute of Medical and Technical Sciences [SIMATS], Saveetha University, Saveetha Nagar, Thandalam, Chennai, Tamilnadu, 602 105, India

    Anita Ramesh

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  1. Vijayashree Priyadharsini Jayaseelan
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  2. Anita Ramesh
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  3. Paramasivam Arumugam
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Contributions

Vijayashree Priyadharsini Jayaseelan: conceptualization, analysis, original draft writing, Anitha Ramesh: reviewing and editing, Paramasivam Arumugam: data curation, writing - reviewing.

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Correspondence to Vijayashree Priyadharsini Jayaseelan.

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The authors declare that they have no conflict of interest.

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Responsible Editor: Mohamed M. Abdel-Daim

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Jayaseelan, V.P., Ramesh, A. & Arumugam, P. Breast cancer and DDT: putative interactions, associated gene alterations, and molecular pathways. Environ Sci Pollut Res 28, 27162–27173 (2021). https://doi.org/10.1007/s11356-021-12489-6

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