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Association between single nucleotide polymorphisms (SNPs) and toxicity of advanced non-small-cell lung cancer

Ling Zhang1, Guanghui Gao, Xuefei Li

  • 1Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Cancer Institute, Shanghai, China.

Plos One
|November 3, 2012
PubMed

Insights

Genetic variations in DNA repair genes, like MMS19L and RRM1, may predict chemotherapy side effects in non-small-cell lung cancer (NSCLC) patients. This research explores these gene polymorphisms to improve treatment tolerability.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Genetic abnormalities in non-small-cell lung cancer (NSCLC) can influence treatment response and sensitivity.
  • The nucleotide excision repair (NER) pathway plays a crucial role in DNA repair and may impact chemotherapy outcomes.

Purpose of the Study:

  • To investigate the association between polymorphisms in NER pathway genes (ERCC5, ERCC6, MMS19L, CCNH, XPC, RRM1) and the tolerability of platinum-based chemotherapy in NSCLC patients.
  • To identify specific genetic markers that predict adverse events associated with chemotherapy in advanced NSCLC.

Main Methods:

  • Genotyping of single nucleotide polymorphisms (SNPs) in NER pathway genes using the AllGloTM probe.
  • Analysis of data from 388 patients with stage IIIB and IV NSCLC who received platinum-based chemotherapy.
  • Statistical correlation of identified polymorphisms with the incidence and severity of chemotherapy-induced adverse events.

Main Results:

  • MMS19L polymorphisms were significantly associated with all-grade leucopenia, jaundice, and creatinine increase, as well as grade 3/4 adverse events and thrombocytopenia.
  • RRM1 polymorphisms correlated with total grade 3/4 adverse events and grade 3/4 vomiting.
  • ERCC5 polymorphisms were linked to an increased incidence of infection.

Conclusions:

  • Specific single nucleotide polymorphisms (SNPs) in NER pathway genes, particularly MMS19L, RRM1, and ERCC5, are correlated with chemotherapy toxicity in advanced NSCLC patients.
  • These findings suggest that NER gene polymorphisms could serve as predictive biomarkers for chemotherapy tolerability, potentially guiding personalized treatment strategies in NSCLC.

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