Abstract 3645: Racial differences in epigenetic modifications of head and neck squamous cell carcinomas: a preliminary study.

Abstract

Abstract Disparities in incidence, mortality and survival are present among head and neck squamous cell carcinoma (HNSCC) patients, with males and African Americans disproportionately affected. Etiologic risk factors for HNSCC include tobacco and alcohol use and human papillomavirus (HPV) infection. Epidemiologically, HPV(+) tumors appreciate a prognostic advantage and have a distinct risk profile compared to HPV(-) HNSCCs. HPV(+) HNSCCs also have a different molecular profile than HPV(-) HNSCCs, specifically a higher somatic mutation rate among HPV(-) tumors and a higher degree of epigenetic modifications among HPV(+) tumors. Although disparities in epigenetic modifications by race have been described for breast, liver and colon cancer, these changes are not well understood among HNSCCs. Here, we described epigenetic modification of candidate genes affecting HNSCC carcinogenesis to understand potential molecular differences in tumor phenotype that may be associated with a distinct racial risk profile in HNSCC patients. We identified formalin-fixed paraffin-embedded (FFPE) HNSCC tissue blocks archived by the Louisiana Cancer Research Consortium Biospecimen Repository for Caucasian and African American patients. Information on site, sex and age was also available. DNA was extracted from tissue collected from areas of >70% cellularity. Using bisulfite sequencing (pyrosequencing), we quantified methylation levels for a panel of candidate genes that have been previously identified as significant in methylation of HNSCCs: CCNA1, CD1A, p16, DCC, GADD45 and NDN. Samples were also tested for HPV status. Using a Mann-Whitney-U test, we compared methylation levels by race, HPV status, sex and age. A total of 24 tissue blocks were retrieved, and we excluded five samples due to inadequate tissue, low DNA concentrations or ambiguous site definitions. The mean age at diagnosis was 56.7 ± 6.5 years and the majority were male (79%). The race distribution was fairly even, with 47.4% African American and 52.6% White. Three HNSCCs were HPV(+), 15 were HPV(-) and one was inconclusive for HPV status. Overall, mean methylation levels were 54.9% for CD1A, 33.9% for CCNA1, 33.5% for DCC, 25.2% for NDN, 6.6% for p16, and 3.4% for GADD45. We noted a significant difference in mean methylation levels of CCNA1 by race (46.8% in African Americans and 19.1% in Whites, p < 0.02). We also found higher methylation levels for CD1A among HPV(+) tumors, 70.7%, compared to HPV(-) tumors, 55.6% (p < 0.04). DCC showed higher methylation levels in males compared to females (38.2% vs. 16.7% respectively; p < 0.04). Our preliminary results suggest that many factors, including race, may be associated with epigenetic modification in HNSCCs, and attention to the somatic profile of HNSCCs may indicate novel avenues for prevention and treatment of this disease. Citation Format: Lauren E. Cole, Laura Rozek, Shama Virani, Maureen Sartor, Jonathon McHugh, Edward Peters. Racial differences in epigenetic modifications of head and neck squamous cell carcinomas: a preliminary study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3645. doi:10.1158/1538-7445.AM2013-3645