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Genetic polymorphisms in cyclin H gene are associated with oxaliplatin-induced acute peripheral neuropathy in South Indian digestive tract cancer patients

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Abstract

Purpose

Digestive tract cancer patients treated with oxaliplatin are often associated with the development of peripheral neuropathy. The aim of the present study is to identify the influence of single-nucleotide polymorphisms (SNPs) in genes involved in oxaliplatin metabolism, cell cycle control, detoxification or excretion pathways with the development of oxaliplatin-induced acute peripheral neuropathy (acute OXAIPN) and its severity among digestive tract cancer patients treated with oxaliplatin-based chemotherapy.

Patients and methods

A total of 228 digestive tract cancer patients undergoing with the oxaliplatin-based chemotherapy between November 2014 and December 2016 were included in the current study. Genomic DNA was extracted from peripheral blood by standard phenol–chloroform method. Genotyping of five SNPs in four genes [GSTP1 (rs1965), ABCG2 (rs3114018), CCNH (rs2230641, rs3093816), AGXT (rs4426527)] was carried out by Real-Time TaqMan SNP genotyping assay.

Results

We found that the two genetic variants rs2230641 and rs3093816 in cyclin H (CCNH) gene were significantly associated with both the incidence and severity of acute OXAIPN. For CCNH-rs2230641 (AA vs AG+GG; dominant model) Incidence: OR 2.62, 95% CI 1.44–4.75, p = 0.001, severity; OR 4.64, 95% CI 1.58–13.62, p = 0.002. For CCNH-rs3093816 (AA vs AG+GG; dominant model); incidence: OR 3.43, 95% CI 1.57–7.50, p = 0.001; severity: OR 2.36, 95% CI 1.05–5.30, p = 0.033.

Conclusions

The results of the present study found significant association between CCNH polymorphisms and acute OXAIPN development. However, further studies are warranted from independent groups to validate our study results.

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Acknowledgements

We sincerely thank the JIPMER (Jawaharlal Institute of Postgraduate Medical Education and Research) for providing the intramural fund (no. JIP/Res/IMF-Ph.D/2014/01) to carry out this study. We also thank the resident doctors of department of Neurology and department of Medical Oncology for their help to carry out this study.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India

    Sreenivasulu Palugulla & Jayanthi Mathaiyan

  2. Unit of Microbiology and Molecular Biology, Vector Control Research Centre, Indian Council of Medical Research, Pondicherry, 605006, India

    Panneer Devaraju

  3. Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India

    Smita Kayal

  4. Department of Neurology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India

    Sunil K. Narayan

Authors
  1. Sreenivasulu Palugulla
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  5. Jayanthi Mathaiyan
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Contributions

JM conceived the study. SP performed the genotyping, laboratory workup and performed statistical analysis. DP, SK and SKN contributed to statistical analysis, writing and critically evaluating the manuscript. JM is the principal investigator and holds the responsibility for the data.

Corresponding author

Correspondence to Jayanthi Mathaiyan.

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Ethical standards

The study was approved by the local institute ethics committee (Reg.no: ECR/342/Inst/PY/2013), JIPMER as well as JIPMER Scientific Advisory Committee (no. JSAC 15/06/2014) and was conducted in accordance with the ethical standards of the Declaration of Helsinki.

Informed consent

Written informed consent, from all the patients, was obtained.

Conflict of interest

We have no conflict of interest.

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Palugulla, S., Devaraju, P., Kayal, S. et al. Genetic polymorphisms in cyclin H gene are associated with oxaliplatin-induced acute peripheral neuropathy in South Indian digestive tract cancer patients. Cancer Chemother Pharmacol 82, 421–428 (2018). https://doi.org/10.1007/s00280-018-3629-1

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  • DOI: https://doi.org/10.1007/s00280-018-3629-1

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