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.

Predictors of Workplace Substance Reuse among Patients with Alcohol or Illegal Substance Use Disorder in the Workplace.

Substance and alcohol use in the workplace have become a global health burden; however, the etiologies have seldom been explored. The aims of this study were to develop a Workplace Substance Reuse Questionnaire (WSRQ) to measure the multidimensional factors associated with the reuse of alcohol or illegal substances in the workplace. The predictors of reuse were also investigated. The WSRQs for alcohol (WSRQ-Alc) and illegal substances (WSRQ-Sub) were composed of 15 and 13 items, respectively. Factors associated with workplace substance reuse included workplace environment, workload, social interaction in the workplace and other cues. Construct validity and reliability were performed to verify the questionnaires. Multivariate linear regression was conducted to estimate the associations between the factors and WSRQ score. A total of 90 patients with substance or alcohol use disorder were recruited. The results demonstrated that the WSRQ-Alc and WSRQ-Sub had acceptable reliability, with variance of 76.4% and 75.4%, respectively. The confirmatory factor analysis fit indices also indicated the adequacy of the model. A longer duration of alcohol use (ß = 0.44; p = 0.002) and higher frequencies of changing job (ß = 0.32; p = 0.027) and working part time (ß = 0.32; p = 0.028) were significantly associated with higher WSRQ-Alc score. Our results highlight the importance of abstinence treatment and job referral for individuals with alcohol or substance use. Further studies are warranted to help extend the applicability and generalizability of the WSRQ.

Effects of Thyroid Hormones on Lipid Metabolism Pathologies in Non-Alcoholic Fatty Liver Disease.

The typical modern lifestyle contributes to the development of many metabolic-related disorders, as exemplified by metabolic syndrome. How to prevent, resolve, or avoid subsequent deterioration of metabolic disturbances and the development of more serious diseases has become an important and much-discussed health issue. Thus, the question of the physiological and pathological roles of thyroid hormones (THs) in metabolism has never gone out of fashion. Although THs influence almost all organs, the liver is one of the most important targets as well as the hub of metabolic homeostasis. When this homeostasis is out of balance, diseases may result. In the current review, we summarize the common features and actions of THs, first focusing on their effects on lipid metabolism in the liver. In the second half of the review, we turn to a consideration of non-alcoholic fatty liver disease (NAFLD), a disease characterized by excessive accumulation of fat in the liver that is independent of heavy alcohol consumption. NAFLD is a growing health problem that currently affects ~25% of the world's population. Unfortunately, there are currently no approved therapies specific for NAFLD, which, if left uncontrolled, may progress to more serious diseases, such as cirrhosis or liver cancer. This absence of effective treatment can also result in the development of non-alcoholic steatohepatitis (NASH), an aggressive form of NAFLD that is the leading cause of liver transplantation in the United States. Because THs play a clear role in hepatic fat metabolism, their potential application in the prevention and treatment of NAFLD has attracted considerable research attention. Studies that have investigated the use of TH-related compounds in the management of NAFLD are also summarized in the latter part of this review. An important take-home point of this review is that a comprehensive understanding of the physiological and pathological roles of THs in liver fat metabolism is possible, despite the complexities of this regulatory axis-an understanding that has clinical value for the specific management of NAFLD.

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.

Serum markers of CYFRA 21-1 and C-reactive proteins in oral squamous cell carcinoma.

BACKGROUND: CYFRA 21-1 (cytokeratin 19 fragment) and C-reactive proteins (CRP) were separately reported to be associated with prognosis of head and neck squamous cell carcinoma. The combined roles of CYFRA 21-1 and CRP levels were rarely investigated in oral squamous cell carcinoma (OSCC). The purpose of the present study was to analyze the relationship between preoperative levels of both CYFRA 21-1 and CRP, with clinicopathological factors and prognosis in OSCC patients. METHODS: A retrospective study was performed on 130 OSCC patients between December 2010 and June 2013. Their serum CYFRA 21-1 and CRP levels were measured preoperatively. RESULTS: CYFRA 21-1 level of ≥3.3 ng/mL and CRP level of ≥5.0 mg/L were significantly associated with pathological tumor status (P<0.001), tumor depth (>10 vs. ≤10 mm, P=0.001), bone invasion (P=0.001), skin invasion (P=0.006), pathologic nodal metastasis (P=0.012), and disease-free survival (P=0.009). Higher CYPFRA 21-1 and CRP levels were also associated with higher risks of distant metastasis (log-rank test, P=0.013, (HR [95% CI]) 1.692 [1.097-2.414]). CONCLUSIONS: Preoperative CYFRA 21-1 and CRP levels are probable candidates as biomarkers for risk stratification in OSCC.