RESUMO
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.
Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias de Cabeça e Pescoço/genética , Paclitaxel/efeitos adversos , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Alelos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Feminino , Genótipo , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Quimioterapia de Indução , Masculino , Proteína 2 Associada à Farmacorresistência Múltipla , Razão de Chances , Paclitaxel/uso terapêuticoRESUMO
Panels composed of Single Nucleotide Polymorphisms (SNPs) in genes related to pigmentation, when associated with different phenotypes, may assist in predicting the physical appearance of an individual, being very useful in forensic caseworks. We evaluated the association of seven OCA2-HERC2 SNPs and haplotypes with pigmentation characteristics (eye, skin, hair and freckles) in the highly admixed and phenotypically heterogeneous Brazilian population. All the seven SNPs evaluated presented one allele associated with phenotypes from at least two pigmentation features and the alternative allele associated with the opposite phenotypes from the same trait. The genotypic associations followed the same pattern for all seven SNPs. Nine haplotypes were observed in our sample and eight were associated with at least two pigmentation traits. Such SNPs and haplotypes could be deemed as good predictors for the presence of freckles and for skin, eye and hair pigmentation in the Brazilian population.