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Breast Cancer
Published in: Breast Cancer 3/2017

01-05-2017 | Original Article

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

Authors: Wei-Chung Hsieh, Che Lin, Dar-Ren Chen, Wen-Fa Yu, Guan-Jie Chen, Suh-Woan Hu, Chin-Chen Liu, Mao-Huei Ge, Chang-Sin Ruan, Cheng-You Chen, Chia-Hua Lin, Po-Hsiung Lin

Published in: Breast Cancer | Issue 3/2017

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Abstract

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 106 nucleotides in controls and breast cancer patients, respectively (~twofold, p < 0.001). In subjects with age <50 or BMI < 27 (kg/m2), 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.
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Metadata
Title
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
Authors
Wei-Chung Hsieh
Che Lin
Dar-Ren Chen
Wen-Fa Yu
Guan-Jie Chen
Suh-Woan Hu
Chin-Chen Liu
Mao-Huei Ge
Chang-Sin Ruan
Cheng-You Chen
Chia-Hua Lin
Po-Hsiung Lin
Publication date
01-05-2017
Publisher
Springer Japan
Published in
Breast Cancer / Issue 3/2017
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-016-0719-y

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