Association between OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and breast cancer risk: a meta-analysis

Abstract

Background: 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. 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.

Methods: We 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.

Results: A 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.

Conclusions: The 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 slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1156934297124915.

Figure 1

Flowchart of selection of studies for inclusion in meta-analysis.

Figure 2

Forest plots of OGG1 Ser326Cys polymorphism and breast cancer risk in subgroup analysis by ethnicity using a fixed-effect model (Recessive model Cys/Cys vs. Ser/Cys + Ser/Ser).

Figure 3

Forest plots of OGG1 Ser326Cys polymorphism and breast cancer risk in postmenopausal patients using a fixed-effect model (Recessive model Cys/Cys vs. Ser/Cys + Ser/Ser).

Figure 4

Funnel plot analysis to detect publication bias. Each point represents a separate study for the indicated association. A Funnel plot for recessive model Cys/Cys vs. Ser/Cys + Ser/Ser of OGG1 Ser326Cys polymorphism in the overall analysis (P = 0.560); B Funnel plot for recessive model Glu/Glu vs. Asp/Glu + Asp/Asp of APEX1 Asp148Glu polymorphism in overall analysis (P = 0.504).