Single-nucleotide polymorphism at alcohol dehydrogenase 1B: A susceptible gene marker in oro-/hypopharyngeal cancers from genome-wide association study.

INTRODUCTION: In the era of precision preventive medicine, susceptible genetic markers for oro-/hypopharyngeal squamous cell carcinoma (OPSCC) have been investigated for genome-wide associations. MATERIALS AND METHODS: A case-control study including 659 male head and neck squamous cell carcinoma (HNSCC) patients, including 331 oropharyngeal cancer, treated between March 1996 and December 2016 and 2400 normal controls was performed. A single-nucleotide polymorphism (SNP) array was used to determine genetic loci that increase susceptibility to OPSCC. RESULTS: We analyzed the allele frequencies of 664,994 autosomal SNPs in 659 HNSCC cases; 7 SNPs scattered in loci of chromosomes 5, 7, 9, 11, and 19 were significant in genome-wide association analysis (Pc < 1.0669 × 10-7 ). In OPSCCs (n = 331), two clustered regions in chromosomes 4 and 6 were significantly different from the controls. We successfully identified a missense alteration of the SNP region in alcohol dehydrogenase 1B (ADH1B) (https://genome.ucsc.edu; hg38); the top correlated locus was rs1229984 (p = 1 × 10-11 ). Adjusted for environmental exposure, including smoking, alcohol, and areca quid, a region in chromosome 12, related to alcohol metabolism, was found to independently increase the susceptibility to OPSCC. The ADH1B rs1229984 AA genotype had better overall survival compared to the AG and GG genotypes (p = 0.042) in OPSCC. The GG genotype in rs1229984 was significantly associated with a younger age of onset than other genotypes (p = 0.001 and <0.001, respectively) in OPSCC patients who consumed alcohol. CONCLUSION: ADH1B was an important genetic locus that significantly correlated with the development of OPSCCs and patient survival.

Carotid arterial blowout after organ preserving chemoradiation therapy in hypopharyngeal cancer.

Laryngeal preserving concurrent chemoradiation has been advocated for hypopharyngeal cancers. The use of radiotherapy (RT) in the larynx could lead to increased rates of radionecrosis. In this study, we investigated a rare but disastrous complication, carotid blow-out syndrome (CBS), related with the persistent radionecrosis. Retrospective cohort study. This retrospective study enrolled hypopharyngeal cancer patients with biopsy-proven pharyngeal and laryngeal chondronecrosis (PLCRN), which was rated by the Chandler Grading System. From 2002 to 2018, a total of 346 hypopharygeal cancer patients received upfront radiation therapy, 13 PLCRN patients were identified in a rate of 3.8%. All PLRN patients received RT with a mean radiation dose of 70.81 ±â€…0.85 Gy. All patients had Chandler Grade IV at the time of presentation, which was a mean of 15.08 months (range: 5-109 months) from the time of cancer diagnosis to PLCRN diagnosis. In 5 of the 13 PLCRN patients developed CBS. Three of the CBS originated from superior thyroid artery, one from lingual artery and one from the carotid artery. Three (60%) of the 5 CBS patients expired due to loss of airway and hemodynamic instability. Two (40%) were rescued by emergent airway secure and emergent angiographic embolization. Persistent PLCRN could lead to disastrous vascular complications. CBSs were demonstrated to be more frequently originated from the branches of carotid artery rather than carotid artery per se. Clinical alert with early airway protection could strive for time to do interventions and prevent mortalities.

Adequacy of Disease Control by Supraomohyoid Neck Dissection in cT1/T2 Tongue Cancer.

BACKGROUND: Patients affected by oral tongue squamous cell carcinoma (OTSCC) underwent a supraomohyoid neck dissection (SOHND) or modified radical neck dissection (mRND) according to the clinical nodal status (cN0 vs. cN+). We investigate whether the type of neck dissection affects survival with the presence of extranodal extension (ENE) and multiple nodal metastases (MNM). METHODS: We conducted a retrospective study enrolling surgically treated patients affected by cT1/T2 OTSCC and MNM or ENE. The outcomes assessed were: overall survival (OS), disease-free survival (DFS), and neck-control- and metastases-free survival (NC-MFS). Survival curves were plotted by the Kaplan-Meier method and the log-rank test. Furthermore, we conducted a multivariable analysis with the Cox regression model. RESULTS: We included a total of 565 patients (36% cT1, 64% cT2). Of these, 501 patients underwent a SOHND, and 64 underwent an mRND. A total of 184 patients presented rpN+, with 28.7% of these in the SOHND group and 62.5% of these in the mRND group. We identified no significant differences in OS, DFS, and NC-MFS in the whole pN+ cohort, in the MNM, and the ENE subgroups. In the multivariable analysis, the type of ND did not affect OS and DFS. CONCLUSIONS: Treating cT1-2 N0/+ tongue cancer with SOHND is oncologically safe. ENE and MNM patients do not benefit from an mRND.

Familial Aggregation of Head and Neck Cancer in Taiwan.

OBJECTIVES: Head and neck cancer (HNC) incidence has been increasing worldwide. We investigated the familial aggregation of developing HNC if a first-degree relative (FDR) is affected in a large database. METHODS: This retrospective study utilized Taiwan National Health Insurance Database to assemble a cohort of all registered beneficiaries from 1997 to 2013 and identified diagnosed HNC patients with affected FDRs. RESULTS: Of the 55,916 individuals diagnosed with HNC, 566 (1.01%) had affected FDRs. There were 525 (0.56%) males and 41 (0.05%) females. Age of onset of HNC was found to be earlier for those with an affected FDR at the fourth decade of life compared to the general population. The adjusted relative risks (RRs) of an individual with an affected FDR to develop HNC is 2.04 (95% confidence interval [CI], 1.85-2.26): 2.07 (95% CI, 1.88-2.29) if the affected relative was male, and 1.74 (95% CI, 1.31-2.30) if the affected relative was female. The greatest risk to develop HNC is if the affected individual is a twin with adjusted RR 33.04 (95% CI, 12.89-84.69). This is followed by an affected sibling at RR (95% CI) 3.46 (1.68-7.13), offspring at RR 2.28 (95% CI, 1.94-2.69), and parent at RR 1.66 (95% CI, 1.48-1.87). CONCLUSION: Familial tendency of HNC proves the probable contribution of genetic factors to develop cancer. In areca quid endemic region, there is a high likelihood that both environmental and genetic factors work in synergy to develop HNC. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:806-812, 2021.

Familial aggregation of nasopharyngeal carcinoma in Taiwan.

BACKGROUND: The incidence of nasopharyngeal carcinoma (NPC) is higher in Chinese than in Caucasian populations. Genetic, viral, and lifestyle factors may explain these ethnic differences in the incidence of NPC. In the present study, we examined the familial aggregation, heritability, and relative risks (RRs) of NPC using a nationwide database in Taiwan. METHODS: A population-based family study was conducted using the Taiwan National Health Insurance Research Database. Participants included all individuals (N=23,422,955) registered with that database in 2013; of these, 17,653 had NPC. Among them, 47.45%, 57.45%, 47.29%, and 1.51% had a parent, child, sibling, and twin, respectively, with NPC. RESULTS: Among the approximately 23 million Taiwan NHI beneficiaries in 2013, the relative risks (RRs) (95% confidence intervals) for NPC were 34.46 (5.12-231.77) for twins of the patients, 9.23 (6.34-13.43) for siblings, 3.80 (2.97-4.86) for parents, 3.74 (2.60-5.37) for offspring, and 1.78 (1.16-2.74) for spouses without genetic similarity. The mean age of onset in first-degree relative-affected NPC patients was 35.5years compared to 39.0years for NPC patients without affected first-degree relatives (p≤0.0001). Using a threshold liability model, the accountability for phenotypic variance of NPC was estimated to be 61.3% for genetic factors (heritability), 13.9% for shared environmental factors, and 24.8% for non-shared environmental factors. The probability of a patient with NPC to be sporadic was 82.8%. CONCLUSION: This population-based analysis suggested a strong familial tendency in the development of NPC. Screening of first-degree relatives of NPC patients is recommended, particularly in endemic regions.