ASPO Abstracts
DNA methylation may modify the associations between pre-diagnosis aspirin use and mortality after breast cancer
Category: Survivorship & Health Outcomes/Comparative Effectiveness Research, Molecular Epidemiology & Environment
Conference Year: 2018
Abstract Body:
Background: We hypothesized that epigenetic changes may help to clarify the underlying biologic mechanism linking aspirin use to breast cancer prognosis. Ours is the first study to examine whether global methylation and/or tumor promoter methylation of breast cancer-related genes interact with aspirin use to impact mortality after breast cancer. Methods: Pre-diagnosis aspirin use was assessed through in-person interviews in a population- based cohort of 1,508 women newly diagnosed with first primary breast cancer in 1996-1997. Global methylation in peripheral blood DNA was assessed by long interspersed elements-1 (LINE-1) and luminometric methylation assay (LUMA). Promoter methylation of 13 breast cancer-related genes were measured in tumor tissue by methylation-specific PCR and Methyl Light. The National Death Index was used to ascertain vital status through December 31, 2014 (N=237/597 breast cancer- specific/all-cause mortality identified). We used Cox proportional hazards regression to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95%CIs). Multiplicative interaction was evaluated using the likelihood ratio test. Results: All-cause mortality after breast cancer was elevated among aspirin ever-users with methylated tumor promotor of BRCA1 (HR=1.67; 95%CI=1.26—2.22), but not those with unmethylated tumors (HR=0.99; 95%CI=0.67—1.45) (p for interaction‰¤0.05). Decreased breast cancer-specific mortality was found among aspirin users with unmethylated tumor promotor of BRCA1 and PR, and global hypermethylation of LINE-1 (HR=0.60, 0.78, and 0.63, respectively; p for interaction‰¤0.05), although the corresponding 95%CIs included the null value. Conclusion: The association between aspirin use and mortality after breast cancer may be modified by tumor promoter methylation of BRAC1 and PR genes, and LINE-1 global methylation.
Keywords: Aspirin, DNA Methylation, Breast Cancer, Mortality