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Updated: Feb 11, 2026

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
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Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung

Sander Bins1, Edwin A Basak1, Samira El Bouazzaoui2

  • 1Department of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, Rotterdam, 3008 AE, The Netherlands.

British Journal of Cancer
|April 27, 2018
PubMed
Abstract

Insights

Investigating single-nucleotide polymorphisms (SNPs) in PD-1 inhibitor-treated NSCLC patients did not predict treatment toxicities. This research provides insights for future biomarker development in immunotherapy.

Area of Science:

  • Immunogenetics
  • Oncology
  • Pharmacogenomics

Background:

  • Immune checkpoint inhibitors (ICIs), such as PD-1 inhibitors, are crucial in cancer treatment but can cause severe immune-related adverse events.
  • Identifying patients at risk for these toxicities is essential for safe and effective immunotherapy.

Purpose of the Study:

  • To identify single-nucleotide polymorphisms (SNPs) associated with treatment-related toxicities in non-small cell lung cancer (NSCLC) patients receiving nivolumab.
  • To explore the pathobiology underlying these toxicities and aid in patient risk stratification.

Main Methods:

  • A cohort of 322 nivolumab-treated NSCLC patients was analyzed.
  • Seven SNPs in four genes (PDCD1, PTPN11, ZAP70, IFNG) involved in PD-1 signaling were assessed for association with toxicity.
  • Significant findings were validated in a separate cohort.

Main Results:

  • In the initial cohort, homozygous variant carriers of PDCD1 804C>T (rs2227981) showed reduced odds of any-grade toxicity (OR 0.4; P=0.039).
  • This association was not replicated in the validation cohort (OR 0.9; P=NS).

Conclusions:

  • The investigated SNPs are unlikely to have clinical utility in predicting nivolumab-induced toxicities.
  • These negative findings are valuable for guiding future research in developing predictive biomarkers for ICI therapy.

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