We conducted a two-stage association study on patients with oropharynx (OP) squamous cell carcinoma (SCC) and healthy controls to identify single nucleotide variants (SNVs) located at the microRNA (miR)-binding sites of carcinogenesis genes associated with risk and prognosis of the disease. In stage 1, 49 patients and 49 controls were analyzed using Genome-Wide Human SNV Arrays to identify variants in the 3′-untranslated region (3′-UTR) of carcinogenesis-related genes, and one SNV was selected for data validation in stage 2 by TaqMan assays in 250 OPSCC patients and 250 controls. The ERP29 c.*293A > G (rs7114) SNV located at miR-4421 binding site was selected for data validation among 46 SNVs. The ERp29 and miR-4421 levels were evaluated by quantitative-PCR and Western blotting. Interaction between miR-4421 with 3′-UTR of ERP29 was evaluated by luciferase reporter assay. Event-free survival (EFS) was calculated by Kaplan–Meier and Cox methods. ERP29 GG variant genotype was more common in OPSCC patients than in controls (6.4% vs 3.6%, p = 0.02; odds ratio: 5.67; 95% confidence interval (CI) 1.27–25.26). Shorter EFS were seen in the base of tongue (BT) SCC patients with GG genotype (0.0% vs 36.2%, p = 0.01; hazard ratio: 2.31; 95% CI: 1.03–5.15). Individuals with ERP29 AG or GG genotypes featured lower levels of ERP29 mRNA (p = 0.005), ERp29 protein (p < 0.001) and higher levels of miR-4421 (p = 0.02). The miR-4421 showed more efficient binding with 3′-UTR of the variant G allele when compared with wild-type allele A (p = 0.001). Our data suggest that ERP29 rs7114 SNV may alter the risk and prognosis of OPSCC due to variation in the ERp29 production possibly modulated by miR-4421.

Cisplatin (CDDP) chemotherapy associated with radiation (RT) has been used in advanced head and neck squamous cell carcinoma (HNSCC) patients, and vomiting is a common side effect during treatment. This prospective study aimed to identify the roles of GSTM1 and GSTT1 (presents or nulls), GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C, ERCC1 c.354C>T, MLH1 c.-93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A, EXO1 c.1765G>A, TP53 c.215G>C, CASP3 c.-1191A>G and c.-1168G>T, CASP9 c.-1339A>G, CASP8 c.-937_-932delAGTAAG, FAS c.-1378G>A and c.-671A>G, and FASL c.-157-687C>T single nucleotide polymorphisms, involved in CDDP metabolism, in vomiting severity in 88 HNSCC patients treated with CDDP and RT. Ondansetron and dexamethasone were administered as anti-emetic therapy. Patients with GSTP1 c.313AG or GG genotype alone and combined with XPD c.934GA or AA, XPF c.2505TC or CC, and CASP9 c.-1339AG or GG genotypes had 4.28, 5.00, 5.45 and 5.38 more chances of presenting moderate/severe vomiting than patients with others genotypes. Our data suggest, for the first time, that inherited abnormality in apoptosis pathway alone or combined with inherited abnormalities in DNA repair pathway, is capable of modulating emesis in HNSCC patients under CDDP chemoradiation and may be used for selecting patients who should receive pre-emptive anti-emetic therapy.

Background: Sociodemographic characteristics and inflammatory cytokines, such as interleukin (IL)-1β, IL-1 cytokine receptor type 2 (IL1R2), IL-6, and triggering receptor expressed on myeloid cells like 2 (TREML2), may influence psychological disorders, including discomfort. Single-nucleotide variants (SNVs) determine individual differences for the modulation of cytokines and indicate that genetics may also influence the comfort levels. However, the relationship between sociodemographic characteristics, holistic comfort, and the roles played by IL1B rs16944, IL1R2 rs4141134, IL6 rs1800795, and TREML2 rs3747742 SNVs on the comfort levels of family caregivers (FCGs) of head and neck cancer (HNC) patients in palliative care (PC) is unknown. Thus, its investigation consisted in the aim of the present study. Methods: A questionnaire was applied to obtain sociodemographic information on 95 FCGs. The genotypes were identified using TaqMan assays. The Holistic Comfort Questionnaire for the Caregiver, which consists of 49 questions, was used to measure comfort levels. Differences between groups were assessed by the t test and linear regression. Results: Employed FCGs ( p  = .04), those youngest ( p  = .04), smokers ( p  = .04), and those with IL1R2 GA or AA genotypes ( p  = .03) presented lower comfort regarding the overall, environmental, sociocultural, and psychospiritual domains, respectively. Conclusions: Employment status, smoking habit, young age, and SNV IL1R2 rs4141134 could influence the comfort levels of FCGs of patients with HNC in PC.

Once considered nonfunctional, pseudogene transcripts are now known to provide valuable information for cancer susceptibility, including head and neck cancer (HNC), a serious health problem worldwide, with about 50% unimproved overall survival over the last decades. The present review focuses on the role of pseudogene transcripts involved in HNC risk and prognosis. We combined current literature and in silico analyses from The Cancer Genome Atlas (TCGA) database to identify the most deregulated pseudogene transcripts in HNC and their genetic variations. We then built a co-expression network and performed gene ontology enrichment analysis to better understand the pseudogenes’ interactions and pathways in HNC. In the literature, few pseudogenes have been studied in HNC. Our in silico analysis identified 370 pseudogene transcripts associated with HNC, where SPATA31D5P, HERC2P3, SPATA31C2, MAGEB6P1, SLC25A51P1, BAGE2, DNM1P47, SPATA31C1, ZNF733P and OR2W5 were found to be the most deregulated and presented several genetic alterations. NBPF25P, HSP90AB2P, ZNF658B and DPY19L2P3 pseudogenes were predicted to interact with 12 genes known to participate in HNC, DNM1P47 was predicted to interact with the TP53 gene, and HLA-H pseudogene was predicted to interact with HLA-A and HLA-B genes. The identified pseudogenes were associated with cancer biology pathways involving cell communication, response to stress, cell death, regulation of the immune system, regulation of gene expression, and Wnt signaling. Finally, we assessed the prognostic values of the pseudogenes with the Kaplan–Meier Plotter database, and found that expression of SPATA31D5P, SPATA31C2, BAGE2, SPATA31C1, ZNF733P and OR2W5 pseudogenes were associated with patients’ survival. Due to pseudogene transcripts’ potential for cancer diagnosis, progression, and as therapeutic targets, our study can guide new research to HNC understanding and development of new target therapies.