Hannah Chang
Pronouns: she/her
Research Mentor(s): Kelly Bakulski
Research Mentor School/College/Department: Epidemiology / Public Health
Program: UROPF
Session: Session 1 (9:00am – 9:50am)
Authors: Hannah Chang, Kelly Bakulski, John Dou
Abstract
Background: Epigenetics is the study of heritable changes in gene activity or function due to environmental factors without changes of the DNA sequence. DNA methylation is a specific epigenetic mechanism by which methyl groups are added to the DNA molecule in regions known as the CpG sites and develop a stable and unique pattern that regulates tissue-specific gene expression [1]. Methylation patterns in blood have been used as biomarkers for environmental exposure effects but not yet used to assess the relationship between alcohol consumption and head and neck squamous carcinoma (HNSC). This study will focus on HNSC tumor samples in the Cancer Genome Atlas, with our goal to assess the relationship between alcohol drinking and DNA methylation in HNSC tumors, to determine whether polymethylation scores can be used as a biomarker in such an association. Methods: Participant characteristics and tumor sample molecular measurements were provided by The Cancer Genome Atlas (TCGA). We calculated the mean and standard deviation for continuous covariates as well as the count and frequency for categorical covariates in alcohol consumption history, the demographics, and tumor characteristics of the patients. Tumor sample DNA methylation was measured using the Illumina HumanMethylation 450k array. For individuals with multiple samples, we eliminated the sample containing the highest probe fail rate. Additional samples were dropped if there was a sex mismatch, probe fail rate >2%, or they were missing alcohol exposure and other covariate data. Polymethylation scores were calculated using summary statistics from an independent published epigenome wide association study of alcohol consumption in blood [2]. We tested the differences in polymethylation score for alcohol consumption using a t-test. Results: In our analytic sample of 418 participants, 267 (64%) have a history of alcohol consumption. Participants with a history of alcohol consumption were younger (mean age 60 versus 64), more likely to be male (78% versus 61%) and were more likely to have tumor stage IV (67% versus 55%), as compared to those without a history of alcohol consumption. Participants with or without a history of alcohol consumption were similar with respect to race/ethnicity (88% White) and cell composition of the tumor (48% epithelial cells). We plan to calculate and compare polymethylation scores between individuals with a history of alcohol consumption and those without such a history, and also conduct a t-test to assess the statistical significance of any differences between their polymethylation scores. Conclusions: Our demographic results show that in the TCGA repository, patients with a history of alcohol use tend to develop HNSC at a younger age and progress into a later stage compared to those without a history of alcohol use. In the near future we will obtain polymethylation scores and determine whether these scores could serve as robust and practical clinical biomarkers of alcohol exposure for HNSC patients. References [1]Moore, L. D., Le, T., & Fan, G. (2012). DNA methylation and its basic function. Neuropsychopharmacology, 38(1), 23–38. https://doi.org/10.1038/npp.2012.112 [2] Liu, C., Marioni, R., Hedman, Å. et al. A DNA methylation biomarker of alcohol consumption. Mol Psychiatry 23, 422–433 (2018). https://doi.org/10.1038/mp.2016.192
