The role of single-nucleotide polymorphism (SNPs) in toxicity of induction chemotherapy based on cisplatin and paclitaxel in patients with advanced head and neck cancer

Pedro De Marchi; Matias E Melendez; Ana C Laus; Pamela A Kuhlmann; Ana Carolina de Carvalho; Lidia Maria R B Arantes; Adriane F Evangelista; Edilene S Andrade; Gilberto de Castro Junior; Rui M Reis; André Lopes Carvalho; Luciano de Souza Viana

doi:10.1016/j.oraloncology.2019.09.013

The role of single-nucleotide polymorphism (SNPs) in toxicity of induction chemotherapy based on cisplatin and paclitaxel in patients with advanced head and neck cancer

Oral Oncol. 2019 Nov:98:48-52. doi: 10.1016/j.oraloncology.2019.09.013. Epub 2019 Sep 17.

Affiliations

¹ Department of Medical Oncology, Barretos Cancer Hospital, Barretos, SP, Brazil. Electronic address: pedrodemarchi@yahoo.com.br.
² Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
³ Universidade do Estado de São Paulo, São Paulo, SP, Brazil.
⁴ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil; Department of Head and Neck Surgery, Barretos Cancer Hospital, Barretos, SP, Brazil.
⁵ Department of Medical Oncology, Barretos Cancer Hospital, Barretos, SP, Brazil.

PMID: 31539757
DOI: 10.1016/j.oraloncology.2019.09.013

Abstract

Background: Induction chemotherapy in locally-advanced head and neck squamous cell carcinoma (LAHNSCC) patients is potentially associated to serious adverse events. Biomarkers associated with toxicity could tailor its indication. This study evaluated the association between single-nucleotide polymorphisms (SNPs) in metabolic genes and toxicity to induction chemotherapy.

Methods: 59 LAHNSCC phase II clinical trial patients (NCT00959387) were assessed regarding 47 metabolic genes (366 SNPs). Toxicities were graded (CTCAE 3.0) and statistical analysis was performed.

Results: The SNPs rs8187710 (ABCC2) and rs1801131 (MTHFR) were associated to increased risk of gastrointestinal toxicity, whereas the SNPs rs3788007 (ABCG1) and rs4148943 (CHST3) were associated to decreased risk. Two other SNPs, rs2301159 (SLC10A2) and rs2470890 (CYP1A2), were associated with increased risk of hematological toxicity. Nevertheless, these SNPs did not remain significant after adjusting for multiple comparisons.

Conclusions: This study could not demonstrate relationship between SNPs and toxicity to induction chemotherapy in LAHNSCC patients. The small number of patients may have affected the results.

Keywords: Head and neck cancer; Induction chemotherapy; LAHNSCC; Pharmacogenomic; SNP; Toxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Antineoplastic Agents / adverse effects*
Antineoplastic Agents / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Cisplatin / adverse effects*
Cisplatin / therapeutic use
Female
Genotype
Head and Neck Neoplasms / diagnosis
Head and Neck Neoplasms / drug therapy
Head and Neck Neoplasms / genetics*
Humans
Induction Chemotherapy
Male
Multidrug Resistance-Associated Protein 2
Odds Ratio
Paclitaxel / adverse effects*
Paclitaxel / therapeutic use
Pharmacogenomic Variants*
Polymorphism, Single Nucleotide*

Substances

ABCC2 protein, human
Antineoplastic Agents
Multidrug Resistance-Associated Protein 2
Paclitaxel
Cisplatin