Abstract

Background. Adenomatous polyposis coli (APC) is widely known as an antagonist of the Wnt signaling pathway via the inactivation of β-catenin. An increasing number of studies have reported that APC methylation contributes to the predisposition to breast cancer (BC). However, recent studies have yielded conflicting results.Methods. Herein, we systematically carried out a meta-analysis to assess the correlation between APC methylation and BC risk. Based on searches of the Cochrane Library, PubMed, Web of Science and Embase databases, the odds ratio (OR) with 95% confidence interval (CI) values were pooled and summarized.Results. A total of 31 articles involving 35 observational studies with 2,483 cases and 1,218 controls met the inclusion criteria. The results demonstrated that the frequency of APC methylation was significantly higher in BC cases than controls under a random effect model (OR = 8.92, 95% CI [5.12–15.52]). Subgroup analysis further confirmed the reliable results, regardless of the sample types detected, methylation detection methods applied and different regions included. Interestingly, our results also showed that the frequency of APC methylation was significantly lower in early-stage BC patients than late-stage ones (OR = 0.62, 95% CI [0.42–0.93]).Conclusion. APC methylation might play an indispensable role in the pathogenesis of BC and could be regarded as a potential biomarker for the diagnosis of BC.

Highlights

  • Breast cancer (BC) is the most common malignancy and the leading cause of cancer death among females in both well and poorly developed countries, accounting for approximately 15% of all cancer deaths in 2012 (Torre et al, 2015)

  • Methylation specific PCR (MSP) was adopted in 17 studies, quantitative real-time methylation specific PCR (MSP) (QMSP) was used in 9 studies, methylation specific-multiplex ligation-dependent probe amplification (MethyLight) was used in 4 studies, methylation specific-multiplex ligation-dependent probe amplification (MS-MLPA) was employed in 2 studies, methylation-sensitive high-resolution melting analysis (MS-HRM) was used in 2 studies and pyrosequencing was used in only 1 study

  • breast cancer (BC) tissues, samples derived from blood and needle aspirated fluid (NAF) were enrolled to assess the methylation levels of the Adenomatous polyposis coli (APC) promoter

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Summary

Introduction

Breast cancer (BC) is the most common malignancy and the leading cause of cancer death among females in both well and poorly developed countries, accounting for approximately 15% of all cancer deaths in 2012 (Torre et al, 2015). How to cite this article Zhou et al (2016), Association between aberrant APC promoter methylation and breast cancer pathogenesis: a meta-analysis of 35 observational studies. An increasing number of studies have reported that APC methylation contributes to the predisposition to breast cancer (BC). The results demonstrated that the frequency of APC methylation was significantly higher in BC cases than controls under a random effect model (OR = 8.92, 95% CI [5.12–15.52]). Subgroup analysis further confirmed the reliable results, regardless of the sample types detected, methylation detection methods applied and different regions included. Our results showed that the frequency of APC methylation was significantly lower in early-stage BC patients than late-stage ones (OR = 0.62, 95% CI [0.42–0.93]).

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