Abstract 1701: Elevated DNA adducts detected in human breast tumors than normal tissues from mammoplasty

Abstract

Abstract Breast cancer is the most common cancer among women worldwide and the second leading cause of cancer-related death in women in the United States. The etiology of the majority of human breast cancers is unknown. Elevated levels of estrogen and exposure to environmental carcinogens have been suggested to be involved in human breast cancer development. Several studies have also provided evidence of the potential role of oxidative stress and lipid peroxidation in breast cancer etiology. Identification of DNA adducts and monitoring change in DNA adduct profiles/burden in normal and cancer tissue may provide clues for risk of breast cancer. In this study, we detected and compared the levels of a wide range of polar to lipophilic adducts in tumor (n= 23) and adjacent normal tissue (n= 30) from breast cancer patients with normal tissue (n=124) from mammoplasty using a 32P-postlabeling adductomics. Adducts were classified into polar (P-1, P-2a and P2b or 8-oxodG) and lipophilic (L-1) in descending order of their polarities. Our results indicated significantly elevated total DNA adduct levels in tumor and adjacent normal tissue of breast cancer patients compared to normal tissues from mammoplasty. The levels of most polar adducts (P-1) were not significantly different among the tumor, adjacent and normal breast tissue. However, relatively lesser polar adducts, i.e., P-2a, P-2b (8-oxodG) and L-1 adducts were significantly higher in tumor and adjacent normal tissues of breast cancer patients compared with normal tissues from mammoplasty. Thus, there is a clear trend of adduct accumulation in the breast tissues of cancer patients that could have acted as a precursor event in carcinogenesis process. Therefore, elevated oxidative DNA adducts such as 8-oxodG can be a possible biomarker for early detection of breast cancer risk and subjects with high DNA adduct load may potentially be at higher risk for cancer development, and could be stratified for chemopreventive intervention. (Supported from CA-90892 and Agnes Brown Duggan Endowment) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1701.