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RAD18 polymorphisms are associated with platinum-based chemotherapy toxicity in Chinese patients with non-small cell

Tian-Qing Chu1, Rong Li1, Min-Hua Shao1

  • 1Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.

Acta Pharmacologica Sinica
|September 27, 2016
PubMed
Abstract

Insights

Genetic variations in RAD18 influence platinum-chemotherapy side effects in Chinese lung cancer patients. These RAD18 polymorphisms are linked to gastrointestinal and hematological toxicities, but not treatment response.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacogenomics

Background:

  • Platinum-based chemotherapy remains a primary treatment for non-small cell lung cancer (NSCLC) lacking targeted therapy biomarkers.
  • Understanding genetic factors influencing treatment efficacy and toxicity is crucial for personalized medicine.

Purpose of the Study:

  • To investigate the association between RAD18 single nucleotide polymorphisms (SNPs) and the response to platinum-chemotherapy.
  • To evaluate the impact of RAD18 SNPs on the incidence of gastrointestinal and hematological toxicities in Chinese NSCLC patients.

Main Methods:

  • A cohort of 1021 Chinese patients with advanced NSCLC receiving first-line platinum-based chemotherapy was analyzed.
  • Ten RAD18 SNPs were genotyped, and treatment response was categorized.
  • Gastrointestinal and hematological toxicities were assessed, and logistic regression was used to analyze associations between SNPs and outcomes.

Main Results:

  • No significant correlation was found between RAD18 SNPs and overall treatment response.
  • Specific RAD18 SNPs (rs586014, rs654448, rs618784) were associated with increased gastrointestinal toxicity, particularly in non-smokers.
  • RAD18 SNPs (rs6763823, rs9880051) showed associations with hematological toxicities, including leukocytopenia, in smokers and non-smokers.

Conclusions:

  • RAD18 polymorphisms play a significant role in predicting platinum-chemotherapy-related side effects in advanced NSCLC patients.
  • These findings suggest potential for using RAD18 genotyping to personalize NSCLC treatment and manage toxicity.

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