Abstract
BackgroundThe base excision repair (BER) pathway removes DNA damage caused by ionizing radiation, reactive oxidative species and methylating agents. ADPRT and APE1 are two important genes in the BER pathway. Several studies have evaluated the association between polymorphisms in the two BER genes (ADPRT Val762Ala and APE1 Asp148Glu) and breast cancer risk. However, the results are inconsistent.Methodology/Principal FindingsIn this study, we conducted a meta-analysis to derive a more precise estimation. A total of 8 studies were included in the meta-analysis (6 studies with 2,521 cases and 2,652 controls for ADPRT Val762Ala polymorphism and 5 studies with 2,539 cases and 2,572 controls for APE1 Asp148Glu polymorphism). For ADPRT Val762Ala polymorphism, no obvious associations were found for all genetic models (Val/Ala vs. Val/Val: OR = 0.960, 95% CI = 0.845–1.090; Ala/Ala vs. Val/Val: OR = 0.897, 95% CI = 0.683–1.178; dominant model: OR = 0.953, 95% CI = 0.843–1.077; and recessive model: OR = 1.084, 95% CI = 0.838–1.403). For APE1 Asp148Glu polymorphism, also no obvious associations were found for all genetic models (Asp/Glu vs. Asp/Asp: OR = 0.947, 95% CI = 0.829–1.082; Glu/Glu vs. Asp/Asp: OR = 0.958, 95% CI = 0.813–1.129; dominant model: OR = 0.946, 95% CI = 0.835–1.072; and recessive model: OR = 1.004, 95% CI = 0.873–1.155). In the subgroup analysis by ethnicity or study design, still no obvious associations were found.Conclusions/SignificanceThis meta-analysis indicates that ADPRT Val762Ala and APE1 Asp148Glu polymorphisms are not associated with increased breast cancer risk.
Highlights
Breast cancer is currently the most common cancer and one of the main causes of cancer-related death in the world, which has become a major public health challenge [1]
All studies indicated that the distribution of genotypes in controls was in agreement with Hardy-Weinberg equilibrium (HWE) and the minor allele frequencies (MAFs) were calculated for the controls (Tables 2)
To the best of our knowledge, this is the first meta-analysis carried out to access the role of adenosine diphosphate ribosyl transferase (ADPRT) Val762Ala and apyrimidine endouclease 1 (APE1) Asp148Glu polymorphisms in breast cancer
Summary
Breast cancer is currently the most common cancer and one of the main causes of cancer-related death in the world, which has become a major public health challenge [1] It is a multifactorial disease caused by complex genetic and environmental factors [2]. Among DNA repair systems, the base excision repair (BER), which is an important pathway responsible for the repair of base damage and single strand breaks caused by X-rays, oxygen radicals, and alkylating agents, has been associated with risk of cancers [3,4,5,6].
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