Genetic polymorphisms in APE1 Asp148Glu(rs3136820) as a modifier of the background levels of abasic sites in human leukocytes derived from breast cancer patients and controls

• Published in: Breast cancer (Tokyo, Japan) Vol. 24; no. 3; pp. 420 - 426
• Main Authors: Hsieh, Wei-Chung, Lin, Che, Chen, Dar-Ren, Yu, Wen-Fa, Chen, Guan-Jie, Hu, Suh-Woan, Liu, Chin-Chen, Ge, Mao-Huei, Ruan, Chang-Sin, Chen, Cheng-You, Lin, Chia-Hua, Lin, Po-Hsiung
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.05.2017; Springer
• Subjects: Adult; Body mass index; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer; Cancer Research; Care and treatment; Case-Control Studies; Development and progression; DNA - metabolism; DNA Damage; DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics; Female; Gene Frequency; Genetic aspects; Genetic polymorphisms; Genetic Predisposition to Disease; Health aspects; Humans; Leukocytes - pathology; Medicine; Medicine & Public Health; Middle Aged; Nucleases; Oncology; Oncology, Experimental; Original Article; Polymorphism, Single Nucleotide; Putrescine - metabolism; Risk factors; Surgery; Surgical Oncology; Oxidative stress; Biomarker; AP sites; DNA repair
• ISSN: 1340-6868; 1880-4233
• DOI: 10.1007/s12282-016-0719-y

Background Apurinic/apyrimidinic (abasic/AP) sites are among the most common endogenous DNA lesions. AP sites, if not repaired, could result in genomic instability as well as chromosome aberrations. Information regarding the direct assay of the number of abasic sites in human leukocytes and its association with risk of breast cancer has not been reported. Methods In this study, we investigated the association between certain risk factors for breast cancer and the background levels of AP sites in leukocytes derived from 148 Taiwanese women with breast cancer and 140 cancer-free controls. The risk factors studied include age, body mass index (BMI), and polymorphisms of apurinic/apyrimidinic endonuclease (APE1) [APE1 Asp148Glu(rs3136820)]. Results Mean levels of AP sites were estimated to be 23.3 and 50.3 per 10 6 nucleotides in controls and breast cancer patients, respectively (~twofold, p  < 0.001). In subjects with age <50 or BMI < 27 (kg/m 2 ), the levels of AP sites in breast cancer patients were ~2–3-fold greater than those of controls ( p  < 0.05). Additionally, results from the AP site 3′-cleavage assay indicated that the AP sites detected in both controls and patients were likely to be oxidant-mediated 5′-cleaved AP sites (~61–64 %). The number of AP sites in breast cancer patients was ~twofold greater in subjects with Asp/Glu + Glu/Glugenotypes than those with Asp/Asp genotype ( p  < 0.001). Conclusions We confirmed that cumulative body burden of AP sites is a significant predictor of the risk of developing breast cancer and that genetic predisposition and environment factors may modulate the induction of oxidative DNA lesions in breast cancer patients.