Abstract

BackgroundThe base excision repair (BER) pathway removes DNA damage caused by ionizing radiation, reactive oxidative species and methylating agents. OGG1 and APE1 are two important genes in the BER pathway. Many epidemiological studies have evaluated the association between polymorphisms in the two BER genes (OGG1 Ser326Cys and APE1 Asp148Glu) and breast cancer risk. However, the results are inconsistent.MethodsWe searched the electronic databases including PubMed, Embase and Cochrane library for all eligible studies for the period up to February 2014. Data were extracted by two independent authors and pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the association.ResultsA total of 17 studies including 9,040 cases and 10,042 controls were available for OGG1 Ser326Cys polymorphism and 7 studies containing 2,979 cases and 3,111 controls were included for APE1 Asp148Glu polymorphism. With respect to OGG1 Ser326Cys polymorphism, we did not find a significant association with breast cancer risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and menopausal status, statistical significant increased breast cancer risk was found in Asian populations (Cys/Cys vs. Ser/Ser: OR = 1.157, 95% CI 1.013–1.321, P = 0.011; Cys/Cys vs. Ser/Cys + Ser/Ser: OR = 1.113, 95% CI 1.009–1.227, P = 0.014) and postmenopausal patients (Cys/Cys vs. Ser/Cys + Ser/Ser: OR = 1.162, 95% CI 1.003–1.346, P = 0.024). In subgroup analysis according to quality score, source of control, and HWE in controls, no any significant association was detected. With respect to APE1 Asp148Glu polymorphism, no significant association with breast cancer risk was demonstrated in the overall and stratified analyses.ConclusionsThe present meta-analysis suggests that the OGG1 Ser326Cys polymorphism may be a risk factor for breast cancer in Asians and postmenopausal patients. Further large and well-designed studies are needed to confirm this association.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1156934297124915

Highlights

  • The base excision repair (BER) pathway removes DNA damage caused by ionizing radiation, reactive oxidative species and methylating agents

  • Study characteristics Based on our search criteria, 24 studies relevant to the role of oxoguanine glycosylase-1 (OGG1) Ser326Cys and APEX1 Asp148Glu polymorphisms on breast cancer susceptibility were identified

  • A total of 17 studies including 9,040 cases and 10,042 controls were available for hOGG1 Ser326Cys polymorphism and 7 studies containing 2,979 cases and 3,111 controls were included for apyimidinic endonuclease 1 (APE1) Asp148Glu polymorphism

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Summary

Introduction

The base excision repair (BER) pathway removes DNA damage caused by ionizing radiation, reactive oxidative species and methylating agents. OGG1 and APE1 are two important genes in the BER pathway. It has been well established that exposure to various endogenous and exogenous mutagens or carcinogens played a critical role in the development of breast cancer [5,6]. The exposures can lead to DNA damage which, if remained unrepaired, may result in genetic instability and unregulated cell growth, and eventually breast cancer [7]. The DNA repairing systems, composed of many DNA repair genes, play a critical role in removing damaged genes resulting from endogenous and exogenous mutagenic exposures, and maintaining the genomic integrity and preventing carcinogenesis

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