Association of alpha globin gene copy number with exhaled nitric oxide in a cross-sectional study of healthy Black adults.

INTRODUCTION: The genetic determinants of fractional exhalation of nitric oxide (FeNO), a marker of lung inflammation, are understudied in Black individuals. Alpha globin (HBA) restricts nitric oxide signalling in arterial endothelial cells via interactions with nitric oxide synthase; however, its role in regulating the release of NO from respiratory epithelium is less well understood. We hypothesised that an HBA gene deletion, common among Black individuals, would be associated with higher FeNO. METHODS: Healthy Black adults were enrolled at four study sites in North Carolina from 2005 to 2008. FeNO was measured in triplicate using a nitric oxide analyzer. The -3.7 kb HBA gene deletion was genotyped using droplet digital PCR on genomic DNA. The association of FeNO with HBA copy number was evaluated using multivariable linear regression employing a linear effect of HBA copy number and adjusting for age, sex and serum immunoglobulin-E levels. Post-hoc analysis employing a recessive mode of inheritance was performed. RESULTS: 895 individuals were in enrolled in the study and 720 consented for future genetic research; 643 had complete data and were included in this analysis. Median (25th, 75th) FeNO was 20 (13, 31) ppb. HBA genotypes were: 30 (4.7%) -a/-a, 197 (30.6%) -a/aa, 405 (63%) aa/aa and 8 (1.2%) aa/aaa. Subjects were 35% male with median age 20 (19, 22) years. Multivariable linear regression analysis revealed no association between FeNO and HBA copy number (ß=-0.005 (95% CI -0.042 to 0.033), p=0.81). In the post-hoc sensitivity analysis, homozygosity for the HBA gene deletion was associated with higher FeNO (ß=0.107 (95% CI 0.003 to 0.212); p=0.045). CONCLUSION: We found no association between HBA copy number and FeNO using a prespecified additive genetic model. However, a post hoc recessive genetic model found FeNO to be higher among subjects homozygous for the HBA deletion.

Predictors of Survival in Veterans with Head and Neck Cancer Treated Surgically.

Background: Squamous cell carcinoma (SCC) accounts for 90% of all head and neck cancers. In veterans, the prevalence of head and neck SCC is nearly twice as high compared with the civilian population. Neck dissection plays an important role in the treatment algorithm for patients with head and neck SCC. The aim of this manuscript was to investigate predictors of survival in patients with head and neck SCC who underwent curative treatment. Methods: Patients with head and neck SCC who underwent treatment with curative intent were included in this study. Data collected included clinical-demographic characteristics, tumor characteristics, and outcome. The primary endpoint was 3-year overall survival (OS), and the secondary endpoints were disease recurrence and distant metastases. Results: A total of 149 patients met inclusion criteria, and most patients were treated with surgery plus adjuvant chemoradiation (52%). The 3-year OS for the entire cohort was 55.7%. There was no statistically significant difference in mortality when comparing the various treatment types. Black patients (hazard ratio [HR] = 1.70, P = .023) and other non-white patients (HR = 3.88, P = .027) had worse 3-year OS compared with white patients. Advanced tumor classification (T4a) was also associated with worse 3-year OS (HR = 3.088, P = .003) and increased risk of cancer recurrence or distant metastases (HR = 3.34, P = .013). Conclusions: Risk factors linked to poor survival among this cohort of veterans with head and neck SCC included non-white race and advanced tumor classification. Neck dissection remains an integral aspect of the treatment algorithm for SCC of the head and neck and can provide regional control of malignant disease.