Abstract
This study aimed to investigate the associations of XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C and ERCC1 c.354C>T single nucleotide polymorphisms (SNPs) of nucleotide excision repair pathway in outcome of head and neck squamous cell carcinoma (HNSCC) patients treated with cisplatin (CDDP) chemoradiation. Patients with XPC c.2815AC or CC and XPD c.934GA or AA genotypes had 0.20 and 0.38 less chances of presenting moderate/severe ototoxicity and nausea, respectively. Patients with XPD c.934AA and c.2251AC or CC genotypes had 8.64, 12.29 and 3.55 more chances of achieving complete response (CR), consistent ototoxicity and nephrotoxicity, respectively. AA haplotype of XPD and ACT haplotype of XPD and ERCC1 SNPs were associated with 9.30 and 3.41 more chances of achieving CR and consistent nephrotoxicity, respectively. At 24 months of follow-up, patients with XPD c.934AA genotype presented lower progression-free survival and overall survival in Kaplan-Meier estimates, and differences between groups remained the same in univariate Cox analysis. Patients with XPD c.934AA genotype had 2.13 and 2.04 more risks of presenting tumor progression and death than others in multivariate Cox analysis. Our data present preliminary evidence that XPC c.2815A>C, XPD c.934G>A and c.2251A>C, and ERCC1 c.354C>T SNPs alter outcome of HNSCC patients treated with CDDP chemoradiation.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common human cancer, with a worldwide incidence of 600,000 new cases and approximately 350,000 deaths are attributed to tumor each year [1].About two-thirds of head and neck squamous cell carcinoma (HNSCC) patients exhibit advanced stage disease at diagnosis [2], and cisplatin (CDDP) associated with radiotherapy (RT) has been used in their treatment [3]
This study aimed to investigate the associations of XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C and excision repair cross-complementation group1 (ERCC1) c.354C>T single nucleotide polymorphisms (SNPs) of nucleotide excision repair pathway in outcome of head and neck squamous cell carcinoma (HNSCC) patients treated with cisplatin (CDDP) chemoradiation
We initially found that clinical and tumor aspects [3, 22, 24, 34, 35], response rate (RR), toxicity to chemoradiation and short survival in advanced tumor stages [3, 34,35,36] in our sample were similar to those previously described in other parts of world
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common human cancer, with a worldwide incidence of 600,000 new cases and approximately 350,000 deaths are attributed to tumor each year [1].About two-thirds of HNSCC patients exhibit advanced stage disease at diagnosis [2], and cisplatin (CDDP) associated with radiotherapy (RT) has been used in their treatment [3]. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common human cancer, with a worldwide incidence of 600,000 new cases and approximately 350,000 deaths are attributed to tumor each year [1]. CDDP develops adducts with cellular DNA www.impactjournals.com/oncotarget and releases free radicals [5]. In both cases, damaged cells are induced to apoptosis when not adequately repaired, by nucleotide excision repair (NER) pathway [6]. The xeroderma pigmentosum (XP) genes, including complementation group C (XPC), D (XPD), F (XPF) and excision repair cross-complementation group (ERCC1), operate in NER pathway, and participate of recognition, demarcation and removal of DNA damage induced by CDDP and RT [7]
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