Dataset Information

Telomere shortening in head and neck cancer: association between DNA demethylation and survival.

ABSTRACT: A growing body of evidence indicates that telomere dysfunction is a biological marker of progression in several types of cancer. However, the association between head and neck squamous cell carcinoma (HNSCC) and telomere length (TL) remains unknown. We measured the absolute TL levels in a well-characterised dataset of 211 tumoral vs normal tissues obtained from the same patients by quantitative polymerase chain reaction assay. Normalised TL levels were significantly lower in tumour samples than in normal tissue (P < 0.001) and there was a positive correlation between tumour tissue and normal mucosal tissue (R² = 0.176, P < 0.001). We were able to distinguish two classes, one with a tumour/normal TL ratio ≤ 0.3 (38.4%), which showed clear telomere erosion, and the other with a tumour/normal TL ratio > 0.3 (61.6%), in which the TL was slightly shorter or longer than that in normal tissue. Notably, the tumour/normal TL ratio was correlated with the likelihood of disease recurrence (P = 0.002), the 5-hydroxymethylcytosine level (P = 0.043), and expression of the ten-eleven translocation (TET) gene (P = 0.043). Our findings show that TL shortening and subsequent low levels of 5-hydroxymethylcytosine and TET expression may contribute to development of HNSCC.

SUBMITTER: Yamada S

PROVIDER: S-EPMC7974875 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Telomere shortening in head and neck cancer: association between DNA demethylation and survival.

Yamada Satoshi S Misawa Kiyoshi K Mima Masato M Imai Atsushi A Mochizuki Daiki D Yamada Taiki T Shinmura Daichi D Kita Junya J Ishikawa Ryuji R Yamaguchi Yuki Y Misawa Yuki Y Kawasaki Hideya H Mineta Hiroyuki H

Journal of Cancer 20210222 8

A growing body of evidence indicates that telomere dysfunction is a biological marker of progression in several types of cancer. However, the association between head and neck squamous cell carcinoma (HNSCC) and telomere length (TL) remains unknown. We measured the absolute TL levels in a well-characterised dataset of 211 tumoral vs normal tissues obtained from the same patients by quantitative polymerase chain reaction assay. Normalised TL levels were significantly lower in tumour samples than ...[more]

PMID: 33758594

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Project description:ImportanceWhile the adverse association between smoking and head and neck squamous cell carcinoma (HNSCC) survival has been well described, there are also inconclusive studies and those that report no significant changes in HNSCC survival and overall mortality due to smoking. There is also a lack of studies investigating the association of marital status on smoking status at diagnosis for patients with HNSCC.ObjectiveTo examine the association between patient smoking status at HNSCC diagnosis and survival and the association between marital status and smoking in these patients.Design, setting, and participantsThis retrospective cohort study was conducted by querying the Saint Louis University Hospital Tumor Registry for adults with a diagnosis of HNSCC and treated at the university academic medical center between 1997 and 2012; 463 confirmed cases were analyzed.Main outcomes and measuresCox proportional hazards regression analysis was used to evaluate association of survival with smoking status at diagnosis and covariates. A multivariate logistic regression model was used to assess whether marital status was associated with smoking at diagnosis adjusting for covariates.ResultsOf the 463 total patients (338 men, 125 women), 92 (19.9%) were aged 18 to 49 years; 233 (50.3%) were aged 50 to 65 years; and 138 (29.8%) were older than 65 years. Overall, 56.2% of patients were smokers at diagnosis (n = 260); 49.6% were married (n = 228); and the mortality rate was 54.9% (254 died). A majority of patients were white (81.0%; n = 375). Smokers at diagnosis were more likely to be younger (ie, <65 years), unmarried, and to drink alcohol. We found a statistically significant difference in median survival time between smokers (89 months; 95% CI, 65-123 months) and nonsmokers at diagnosis (208 months; 95% CI, 129-235 months). In the adjusted Cox proportional hazards model, patients who were smokers at diagnosis were almost twice as likely to die during the study period as nonsmokers (hazard ratio, 1.98; 95% CI, 1.42-2.77). In the multivariate logistic regression analysis, unmarried patients were 76% more likely to use tobacco than married patients (adjusted odds ratio, 1.76; 95% CI, 1.08-2.84).Conclusions and relevanceSmokers were almost twice as likely as nonsmokers to die during the study period. We also found that those who were married were less likely to be smokers at diagnosis. Our study suggests that individualized cancer care should incorporate social support and management of cancer risk behaviors.

Project description:ImportanceDiagnostic delay can negatively affect patient outcomes in head and neck cancer (HNC). Neck mass and other symptoms of undiagnosed HNC may be treated with antibiotics, delaying diagnosis and treatment, despite current clinical practice guidelines.ObjectiveTo investigate temporal trends, associated factors, and time from symptom onset to antibiotic prescribing before an HNC diagnosis.Design, setting, and participantsA retrospective cohort study was conducted using data obtained from a deidentified electronic health records data set from January 1, 2011, to December 31, 2018. Patients with HNC enrolled in the data set for at least 1 year before diagnosis date determined by either 1 inpatient encounter or first of 2 outpatient encounters within 6 months were included. Data analysis was conducted from May 1 to November 9, 2022.ExposureAntibiotic prescription within 3 months before HNC diagnosis date.Main outcomes and measuresThe primary outcome was days from the first documented symptom to HNC diagnosis.ResultsThe cohort included 7811 patients with HNC (4151 [53.1%] men, mean [SD] age, 60.2 [15.8] years). At least 1 antibiotic was prescribed for 1219 patients (15.6%) within 3 months before HNC diagnosis. This represented an increase over the 8.9% prescribing rate during the baseline period 12 to 9 months before diagnosis. The rate of antibiotic prescribing within 3 months before diagnosis did not change significantly over time (quarterly percent change, 0.49%; 95% CI, -3.06% to 4.16%). Patients receiving an antibiotic prescription within 3 months of an HNC diagnosis had a 21.1% longer time between symptom onset and HNC diagnoses (adjusted rate ratio [ARR], 1.21; 95% CI, 1.14-1.29). Compared with diagnosis by otolaryngologists, primary care/internal medicine physicians were most likely to prescribe antibiotics for patients who were diagnosed with a presenting symptom (adjusted prevalence ratio, 1.60; 95% CI, 1.27-2.02). In patients presenting with neck mass/swelling, those presenting with other symptoms were more likely to have longer intervals from symptom onset to diagnosis (ARR, 1.31; 95% CI, 1.08-1.59).Conclusions and relevanceThe findings of this cohort study suggest there is an increased rate of antibiotic prescription in the 3 months before HNC diagnosis, which is associated with an increased time to diagnosis. These findings identify an area for improvement in HNC care and guidelines.

Dataset Information

Telomere shortening in head and neck cancer: association between DNA demethylation and survival.

Publications

Telomere shortening in head and neck cancer: association between DNA demethylation and survival.

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