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Association of PARK-2 Non-synonyms Polymorphisms and Their In Silico Validation Among North Indian Colorectal Cancer Patients

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Abstract

Purpose

PARK2 is a potential tumour suppressor gene and its genetic alterations (regionic loss) are common across many human cancers. The association of PARK2 germline variations (SNPs) with Parkinson’s has been shown, but their association in development and progression of cancer remains elusive. The aim of this study was to identify association of PARK2 polymorphisms (rs1801474, rs1801334) with colorectal cancer in a case control study design.

Methods

This case control study included a total of 650 genetically unrelated subjects comprising 300 colorectal cancer cases and 350 healthy controls belonging to North Indian. Both SNPs were analyzed using the PCR–RFLP assay. Statistical analysis for describing risk and association was performed using SPSS-17 software. Structural deviations due to non- synonymous substitutions (S167N and D394N) were analyzed using MD simulations.

Results

The genotype distributions of both the SNPs were in Hardy–Weinberg equilibrium. For both the polymorphisms, the allelic model showed statistically significant risk with OR ~ 1.3. Many of the associations remained significant even after Bonferroni correction (P < 0.00125). The result suggested that both S167N and D394N were deviated from wild type and structures and were stable after 5 ns. The average value of RMSD for backbone atoms was calculated from 5 to 10 ns molecular dynamics simulation data.

Conclusion

In conclusion, our study revealed a significant association of PARK2 SNPs with colorectal cancer as well as their relations with other clinical parameters highlighting their contribution towards colorectal cancer susceptibility in North Indian population.

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Data Availability

The data sets generated during the study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors acknowledge MANF-UGC, Government of India, New Delhi, for proving the fellowship to ZIB.

Author information

Authors and Affiliations

  1. Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India

    Zafar Iqbal Bhat, Afreen Naseem, Raj Ranjan Tiwari & M. Moshahid Alam Rizvi

  2. Department of Biochemistry, Institute of Home Economics, University of Delhi, Delhi, India

    Bhupender Kumar

  3. Synthetic Biology Lab, School ofBiotechnology, Jawaharlal Nehru University, New Delhi, India

    Kalaiarasan Ponnusamy

  4. Department of Zoology, P.M.B Gujarati Science College, Indore, India

    G. D. Sharma

Authors
  1. Zafar Iqbal Bhat
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  2. Afreen Naseem
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  3. Bhupender Kumar
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  4. Kalaiarasan Ponnusamy
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  5. Raj Ranjan Tiwari
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  6. G. D. Sharma
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  7. M. Moshahid Alam Rizvi
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Contributions

ZI and AN designed the study and conducted the experiments and wrote the manuscript. BK helped in manuscript review and statistical analysis. PK provided the in silico support. RT helped in conducting experiments and in sample collection. GS and MMAR provided the concept and overall support.

Corresponding author

Correspondence to M. Moshahid Alam Rizvi.

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Ethics Approval

The medical ethics committee of Jamia Millia Islamia reviewed and approved this study design (permission number: 21–01-01–07).

Consent to Participate

All patients and their families were informed about the surgical procedure and provided their written consent. Informed broad consent for this study was obtained.

Consent for Publication

Informed broad consent for this study was obtained.

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The authors declare no competing interests.

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Bhat, Z.I., Naseem, A., Kumar, B. et al. Association of PARK-2 Non-synonyms Polymorphisms and Their In Silico Validation Among North Indian Colorectal Cancer Patients. J Gastrointest Canc 53, 674–682 (2022). https://doi.org/10.1007/s12029-021-00693-z

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  • DOI: https://doi.org/10.1007/s12029-021-00693-z

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