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Mutational analysis of head and neck squamous cell carcinoma stratified by smoking status.

ABSTRACT: Smoking has historically been recognized as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). This study aimed to assess the mutational differences between heavy smokers (>20 pack years) and never smokers among the HNSCC patients within The Cancer Genome Atlas (TCGA). Single nucleotide variation and copy number aberration differences between heavy smokers and never smokers were compared within human papillomavirus-positive (HPV-positive) (n = 67) and HPV-negative (n = 431) TCGA cohorts with HNSCC, and the impact of these mutations on survival were assessed. No genes were differentially mutated between smoking and never-smoking patients with HPV-positive tumors. By contrast, in HPV-negative tumors, NSD1 and COL1A11 were found to be more frequently mutated in heavy smokers, while CASP8 was more frequently altered in never smokers. HPV-negative patients with NSD1 mutations experienced significantly improved overall survival compared with NSD1 WT patients. This improved prognosis was validated in an independent cohort of 77 oral cavity cancer patients and a meta-analysis that included 2 additional data sets (688 total patients, hazard ratio for death 0.44, 95% CI, 0.30-0.65). NSD1 mutations are more common in HPV-negative heavy smokers, define a cohort with favorable prognosis, and may represent a clinically useful biomarker to guide treatment deintensification for HPV-negative patients.

SUBMITTER: Ghasemi F

PROVIDER: S-EPMC6485669 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Mutational analysis of head and neck squamous cell carcinoma stratified by smoking status.

Ghasemi Farhad F Prokopec Stephenie D SD MacNeil Danielle D Mundi Neil N Gameiro Steven F SF Howlett Christopher C Stecho William W Plantinga Paul P Pinto Nicole N Ruicci Kara M KM Khan Mohammed Imran MI Yoo John J Fung Kevin K Sahovaler Axel A Palma David A DA Winquist Eric E Mymryk Joe S JS Barrett John W JW Boutros Paul C PC Nichols Anthony C AC

JCI insight 20190110 1

Smoking has historically been recognized as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). This study aimed to assess the mutational differences between heavy smokers (>20 pack years) and never smokers among the HNSCC patients within The Cancer Genome Atlas (TCGA). Single nucleotide variation and copy number aberration differences between heavy smokers and never smokers were compared within human papillomavirus-positive (HPV-positive) (n = 67) and HPV-negative (n ...[more]

PMID: 30626742

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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.

Dataset Information

Mutational analysis of head and neck squamous cell carcinoma stratified by smoking status.

Publications

Mutational analysis of head and neck squamous cell carcinoma stratified by smoking status.

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