Analysis of the Abasic Sites in Breast Cancer Patients With 5 Year Postoperative Treatment Without Recurrence in Taiwan

• Published in: Cancer control Vol. 31; p. 10732748241300656
• Main Authors: Lin, Che, Feng, Chi-Yen, Bahari, Gilang P., Huang, Sheng-Min, Wei, Cheng-Hao, Xu, Qi, Dinh, Dat Thanh, Chen, Dar-Ren, Lin, Po-Hsiung
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.11.2024; Sage Publications Ltd; SAGE Publishing
• Subjects: Adult; Aged; Alleviating the Burden of Cancer through Prevention and Early Detection; Apyrimidinic sites; Background levels; Breast cancer; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Carcinogenesis; DNA adducts; DNA Damage; Estrogens; Exonuclease; Female; Humans; Middle Aged; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - pathology; Nucleotides; Oxidative stress; Prospective Studies; Putrescine; Taiwan - epidemiology; Taiwan; abasic sites; biomarker; DNA repair; DNA damage; oxidative stress
• ISSN: 1073-2748; 1526-2359; 1526-2359
• DOI: 10.1177/10732748241300656

Purpose This prospective study aimed to investigate estrogen-induced carcinogenesis by assessing the background levels of abasic sites (apurinic/apyrimidinic sites, AP sites) in Taiwanese breast cancer patients following 5 years of postoperative treatment without recurrence (5-year survivors) (n = 70). The study also sought to compare the extent of these DNA lesions with those found in healthy controls and in breast cancer patients prior to treatment. Methods Abasic sites were measured using an aldehyde reactive probe and quantified as the total number of abasic sites per total nucleotides. Characterization of the abasic sites in subjects recruited for this study was conducted using the abasic site cleavage assay using putrescine or T7 exonuclease (T7 Exo) and/or exonuclease III (Exo III). Results The number of abasic sites detected in 5 year survivors (26.7 ± 10.2 per 106 total nucleotides, n = 70) was significantly reduced by 46.9% compared to those in breast cancer patients before treatment (50.3 ± 59.2 per 106 total nucleotides, P < 0.001), and was similar to the levels observed in healthy controls (23.3 ± 13.5 per 106 total nucleotides, P > 0.05). Further investigation into the specific types of abasic sites indicated that the number of abasic sites excisable by putrescine in controls, breast cancer patients, and 5-year survivors were 63.3%, 78.6%, and 67.7%, respectively. These findings suggest the involvement of oxidative stress rather than depurination/depyrimidination of DNA adducts in the formation of abasic sites. Further analyses were performed using exonuclease cleavage assay to characterize the specific types of abasic sites including 5′-cleaved, 3′-cleaved, intact, and residual abasic sites. Results demonstrated that the proportion of residual abasic sites detected in controls, breast cancer patients, and 5-year survivors were estimated to be 32.7%, 48.8%, and 34.0%, respectively. Conclusion Overall, these findings suggest clear evidence of treatment-related effects on the reduction of levels of abasic sites as well as on the profile of abasic sites in 5 year survivors. Plain language summary Purpose This study aimed to analyze the impact of estrogen on cancer development by measuring the baseline levels of abasic sites—specific types of DNA damage—in Taiwanese breast cancer patients who have survived for five years post-treatment without recurrence. The study compared these levels with those in healthy individuals and breast cancer patients prior to treatment. Methods The study measured abasic sites using an aldehyde reactive probe, assessing them per total nucleotides. The nature of these sites was further analyzed using assays that detect specific cleavages by putrescine, T7 exonuclease, or exonuclease III. Results The findings showed a significant reduction (approximately 47%) in abasic sites in patients five years post-treatment compared to those observed before treatment. The levels in long-term survivors were similar to those in healthy controls. Most of the abasic sites in the study were linked to oxidative stress rather than the breakdown of DNA itself. Additional detailed analysis of these sites was performed, identifying different types of abasic damages. Conclusion The study provides strong evidence that treatment significantly reduces the levels of abasic sites and alters their composition, which may be an important factor in the lack of recurrence in these patients.