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Association of ABCC4 G559T single nucleotide polymorphism with arsenic-induced precancerous hyperkeratosis

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Abstract

Chronic arsenic toxicity, a global health issue, leads to multiple skin cancers. Only 15–20% of exposed individuals ever develop arsenic-specific skin lesions highlighting the role of genetic polymorphisms in inter-individual susceptibility. Multidrug resistance proteins (MRPs), encoded by ATP binding cassette transporter subfamily C (ABCC) genes are demonstrated to efflux arsenic metabolites. MRP4 encoded by ABCC4 is a high-affinity efflux transporter of diglutathionylated monomethyl arsonous acid [MMA(GS)2] and dimethyl arsenic acid (DMAV).The association of ABCC4 polymorphisms with arsenic-disease susceptibility is unknown. The possible association of five previously characterized non-synonymous ABCC4 SNPs with arsenic-induced premalignant hyperkeratosis was examined in the study. A total of 230 study participants were recruited from the highly arsenic-exposed district of Murshidabad in West Bengal, India (136 cases with arsenic-induced premalignant hyperkeratosis; 94 controls with no arsenic-specific skin lesions). Cases and controls were matched in exposure status and demographic variables apart from age. Exposure assessment was performed by total arsenic content analysis of water and urine, while genoty** was performed employing PCR-Sanger sequencing or PCR-RFLP. Our population was monomorphic for 4 of the 5 SNPs studied. Age-adjusted Odds ratio showed the presence of at least one T allele for ABCC4 codon polymorphism confers protection against premalignant hyperkeratosis [OR (95% CI): 0.994 (0.888–0.998)].

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Data and material regarding the present study are available with the corresponding author and can be shared on request.

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Acknowledgements

Authors are thankful to Mr. Rhitwik Chatterjee, Geologist, Murshidabad district, West Bengal for hel** us in arranging the medical camps in remote villages of Murshidabad district and Dr. Sandip Bhattacharjee for medical supervision during biological sample collection.

Funding

PB was supported funding from University of Calcutta (Grant No. BI: 166/21). EML was supported by Canadian Institute of Health Research grant (MOP-272075). MB was supported by an Alberta Cancer Foundation Cancer Research Postdoctoral Fellowship Award. TS was supported by University Grants Commission—Senior Research Fellowship (India). None of the funding sources had any involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Author information

Author notes

  1. Mayukh Banerjee

    Present address: Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, 40202, USA

Authors and Affiliations

  1. Environmental Epigenomics Lab, Department of Environmental Science, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India

    Tamalika Sanyal, Sunandini Ghosh & Pritha Bhattacharjee

  2. CSIR-Indian Institute of Chemical Biology, 4, Raja Subodh Chandra Mallick Rd, Kolkata, West Bengal, 700032, India

    Ashok K. Giri

  3. Department of Physiology, University of Alberta, Edmonton, AB, T6G 2H7, Canada

    Elaine M. Leslie & Mayukh Banerjee

  4. Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, T6G 2H7, Canada

    Elaine M. Leslie

  5. Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB, T6G 2H7, Canada

    Elaine M. Leslie & Mayukh Banerjee

  6. Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India

    Tamalika Sanyal & Sunandini Ghosh

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  1. Tamalika Sanyal
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Contributions

TS: Investigation, Data curation, Writing—review and editing, Visualization; SG: Investigation, Data curation, Writing—review and editing, Visualization; AKG: Methodology, Data curation; EML: Conceptualization, Funding acquisition, Project administration, Writing—review and editing; MB: Conceptualization, Funding acquisition, Formal analyses, Writing—original draft, Writing—review and editing, Visualization; PB: Conceptualization, Funding acquisition, Project administration, Supervision, Writing—review and editing.

Corresponding author

Correspondence to Pritha Bhattacharjee.

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The authors declare that they have no conflict of interest.

Ethics approval and consent to participation

The study was approved by the ethical review committee of the University of Calcutta, India (CU/BIOETHICS/HUMAN/1391) as well as the University of Alberta human ethics review board (Protocol Number 69336). Informed and written consent to participation was obtained from the study participants matching the inclusion criteria.

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Informed consent to publication was obtained from the study subjects.

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Corresponding Editor: Somnath Paul; Reviewers: Nilanjana Banerjee, Jeison Garcia Serrano.

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Sanyal, T., Ghosh, S., Giri, A.K. et al. Association of ABCC4 G559T single nucleotide polymorphism with arsenic-induced precancerous hyperkeratosis. Nucleus (2023). https://doi.org/10.1007/s13237-023-00440-8

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