Race as a social construct in head and neck cancer outcomes.

OBJECTIVE: The authors examined ancestry informative markers (AIMs) to estimate the amount of population admixture and control for this heterogeneity for stage and survival in a primary head and neck squamous cell carcinoma (HNSCC) cohort. STUDY DESIGN: Historical cohort study. SETTING: Integrated health care system. SUBJECTS: The cohort comprised 358 patients with HNSCC who self-reported race as Caucasian American (CA), African American (AA), or other. METHODS: DNA was interrogated for West African (WA) and European genetic background by genotyping AIMs. Associations of race (self-report or WA ancestry) with stage and survival were analyzed using logistic regression and Cox regression modeling. A subgroup analysis for diagnosis (late vs early stage) and survival (time to death) and WA ancestry was performed for self-reported AAs. RESULTS: There were significant associations between stage and self-reported race (P = .04 [univariate]) and with cancer site (oropharynx: P = .014; hypopharynx: P = .026 [multivariate]). For prognosis, there were significant multivariate associations between stage (P = .002), age (>65 years, P < .001), and cancer site (hypopharynx: P < .001; oral cavity: P = .049), but self-reported race was not associated with overall survival. Interestingly, there was no association with degree of WA ancestry and stage or survival. In the subgroup analysis of genetic ancestry among self-reported AAs, cancer site remained an independent risk factor for stage (other site: P = .026) and survival (oropharynx: P = .036). Late stage persisted as an independent variable for poor survival (P = .032). CONCLUSIONS: Stratification within AAs by WA ancestry revealed no correlation with stage or survival, suggesting that HNSCC outcomes with race may be owing to social/behavior factors rather than biological differences.

Novel approaches to global mining of aberrantly methylated promoter sites in squamous head and neck cancer.

OBJECTIVE: Promoter hypermethylation is emerging as a promising molecular strategy for early detection of cancer. We examined promoter methylation status of 1143 cancer-associated genes to perform a global but unbiased inspection of methylated regions in head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Laboratory-based study. SETTING: Integrated health care system. SUBJECTS AND METHODS: Five samples, two frozen primary HNSCC biopsies and three HNSCC cell lines, were examined. Whole genomic DNA was interrogated using a combination of DNA immunoprecipitation (IP) and Affymetrix whole-genome tiling arrays. RESULTS: Of the 1143 unique cancer genes on the array, 265 were recorded across five samples. Of the 265 genes, 55 were present in all five samples, and 36 were common to four of five samples, 46 to three of five, 56 to two of five, and 72 to one of five samples. Hypermethylated genes in the five samples were cross-examined against those in PubMeth, a cancer methylation database combining text mining and expert annotation (http://www.pubmeth.org). Of the 441 genes in PubMeth, only 33 are referenced to HNSCC. We matched 34 genes in our samples to the 441 genes in the PubMeth database. Of the 34 genes, eight are reported in PubMeth as HNSCC associated. CONCLUSION: This pilot study examined the contribution of global DNA hypermethylation to the pathogenesis of HNSCC. The whole-genome methylation approach indicated 231 new genes with methylated promoter regions not yet reported in HNSCC. Examination of this comprehensive gene panel in a larger HNSCC cohort should advance selection of HNSCC-specific candidate genes for further validation as biomarkers in HNSCC.