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Meta-analysis of polymorphic variants conferring acute lymphoblastic leukemia risk in the Indian population

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Abstract

Acute lymphoblastic leukemia (ALL) is a rapidly progressive bone marrow cancer in which early lymphoid precursors proliferate and replace the normal bone marrow hematopoietic cells. Although it is regarded as the most preponderant case of childhood cancer, ALL can also occur in adults. In India, ~ 6000 children are diagnosed with ALL each year. The disease etiology is complex and yet not fully elucidated. Several gene polymorphisms have been investigated across the globe, with regards to susceptibility towards ALL, often revealing contradictory or inconclusive results of genetic associations. In this meta-analysis, we have attempted to identify all the polymorphisms (and genes) tested for association with ALL from India to date to derive a more precise association of the variants with the disease risk, collating all the studies together. A meta-analysis conducted on 30 polymorphisms belonging to 19 genes identified rs3892097/CYP2D6, rs4646903/CYP1A1*2A, del1/GSTT1, rs1695/GSTP1 and rs1045642/ABCB1 to be genetic risk factors of ALL in the Indian population. Considering the association of rs3892097/CYP2D6 with ALL in dominant, recessive as well as additive models in the Indian context, further meta-analysis was done for the variant with data from across the world and the significance persisted yet. Covariates such as mean age and rural settlement were found to have an overall association with the risk of ALL. This study is the first of its kind from India, determining with better confidence the genetic risk factors ALL that may pave the way towards precision medicine and the genetic risk factors of ALL that may pave the way towards precision medicine and, thus, proper treatment of the malady.

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Data availability

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Abbreviations

ALL:

Acute lymphoblastic leukemia.

GWAS:

Genome-wide association studies.

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

SNP:

Single nucleotide polymorphisms.

SNV:

Single nucleotide Variants.

FE meta-analysis:

Fixed effect meta-analysis.

RE meta-analysis:

Random effect meta-analysis.

FDR:

False discovery rate

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Acknowledgements

We sincerely acknowledge Prof. Anshuman Lahiri (Dept. of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, Kolkata ) for his critical reading and correcting the manuscript.

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  1. Sutanuka Sengupta and Debmalya Sengupta have equally Contributed to this work.

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  1. Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, Kolkata, India

    Sutanuka Sengupta

  2. Department of Genetics, University of Calcutta, Kolkata, India

    Debmalya Sengupta, Souradeep Banerjee, Bratati Dutta & Mainak Sengupta

  3. University College of Science (UCSTA), 35, Ballygunge Circular Road, Kolkata, 700 019, India

    Mainak Sengupta

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SS and DS: Text mining, analysis and drafting of the manuscript; SB and BD: Text mining and curating and formatting the data files; MS: conceptualisation of the work, critical reading and correcting the manuscript and overall supervision;

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Sengupta, S., Sengupta, D., Banerjee, S. et al. Meta-analysis of polymorphic variants conferring acute lymphoblastic leukemia risk in the Indian population. Nucleus (2024). https://doi.org/10.1007/s13237-024-00466-6

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