Dna Methylation Age Of Paired Tumor-Normal Breast Tissue In Chinese Women With Breast Cancer

Background: Epigenetic age, captured by DNA methylation changes, is thought to be more informative with respect to disease risk and progression, than chronological age. A few studies have associated epigenetic age acceleration (EAA), the difference between DNA methylation age (DNAm age) and chronological age, with BC risk and subtypes. However, most of these studies were conducted in Western populations. In this study, we examined EAA in an Asian population, in which BC incidence rate is lower and age at BC onset is younger compared to most Western populations. Methods: We performed genome-wide DNA methylation profiling of 97 tumor and 89 paired distant normal tissue samples collected from BC patients in Hong Kong (HK) using an Illumina MethylationEPIC array. Two independent datasets were used to compare results: The Cancer Genome Atlas (TCGA, n=525 tumor and n=88 adjacent normal) and healthy women from the Komen tissue bank (n=59). DNAm age was calculated using Horvath9s model based on 353 CpGs. The significance of EAA was tested using a simple linear regression model. We also used a multivariate regression model to test for equality of slopes (EAA rates) among different BC subtypes or datasets, considering interaction terms between age and subtype/dataset. Results: The average age at BC diagnosis was 58 years old (range: 33-81) and the distribution of the molecular subtype based on PAM50 was 43.0%, 29.1%, and 27.9% for luminal A, luminal B, and HER2-enriched/basal tumors, respectively. As expected, DNAm age showed a stronger correlation with chronological age in normal tissue (r=0.78, p Conclusion: Consistent with previous studies, we found that EAA in tumor samples varied across tumor subtypes. We also found that HK BC patients9 epigenetic age accelerated at a different rate compared to predominantly white TCGA and Komen women, suggesting a potential racial biological difference. Large studies in other Asian populations are warranted to confirm our findings, which may provide biological insight into racial heterogeneity of BC, especially with regard to age at onset. Citation Format: Hela Koka, Bin Zhu, Shelly Lap Ah Tse, Difei Wang, Maeve Kiely, Jennifer Lyn Guida, Priscilla Lee, Feng Wang, Cherry Wu, Koon Ho Tsang, Wing-cheong Chan, Sze Hong Law, Eric Karlins, Bin Zhu, Amy Hutchinson, Belynda Hicks, Xiaohong R. Yang. DNA methylation age of paired tumor-normal breast tissue in Chinese women with breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 146.