Abstract 2271: DNMT1 expression is peripheral mononuclear cells is associated with increased breast cancer risk

Abstract

Abstract Loss of global DNA methylation in peripheral tissue has been identified as a biomarker of breast cancer susceptibility in several studies. DNA methyl-transferases or DNMTs are the enzymes in charge of catalyzing the addition of the methyl group to the DNA molecule. Of the different DNMTs described in humans, only DNMT1 has been found to be in charge of adding methyl groups to the newly synthesized DNA strand. Therefore, compromised levels of this enzyme might lead to a loss of global DNA methylation and concomitantly an increase in breast cancer risk. However, to date no study has examined the association between peripheral levels of DNMT1 and breast cancer. To investigate this relation, we conducted a case-control study including sisters in the New York site of the Breast Cancer Family Registry. We extracted mRNA from peripheral mononuclear cells (PMNC) in 196 sister sets, a total of 479 female participants, and assayed DNMT1 gene expression levels using Taqman expression assays. The results were analyzed using generalized estimating equations (GEE). We found that there were no large differences between the mean levels of DNMT1 expression levels of women with breast cancer and controls; mean level in cases was 0.46 ± 0.71 versus 0.63 ± 1.42 in controls (p=0.10). When examining expression levels as a continuous variable, there also were no associations in GEE regression models adjusting for age at blood drawn and smoking status Odds Ratio (OR) = 1.17 (95% confidence interval (CI) = 0.97 - 1.40 per one unit increase in expression levels), p=0.11). However, when results were analyzed by categorizing DNMT1 expression in tertiles, lower DNMT1 expression (≤ 0.17%) was associated with statistically significantly higher odds of breast cancer (OR = 1.47 (95%CI = 1.02 - 2.10), p=0.04). If replicated in other studies, these findings suggest that low DNMT1 expression in PBMC has the potential to be used as a biomarker of breast cancer risk in women at high risk of the disease. Citation Format: Lissette Delgado-Cruzata, Xinran Ma, Yuyan Liao, Maya Kappil, Regina M. Santella, Mary Beth Terry. DNMT1 expression is peripheral mononuclear cells is associated with increased breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2271. doi:10.1158/1538-7445.AM2017-2271