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Two-stage case–control study of DNMT-1 and DNMT-3B gene variants and breast cancer risk

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Abstract

Aberrant DNA methylation of CpG islands is a common epigenetic alteration found in cancers. DNA methylation is typically mediated by DNA methyltransferases (DNMTs). Only two studies have evaluated DNMT-1 and/or DNMT-3B gene polymorphisms in relation to breast cancer risk, and results have been inconsistent. We comprehensively evaluated genetic variations in the DNMT-1 and DNMT-3B genes with breast cancer risk among the participants of the Shanghai Breast Cancer Study, a large-scale, two-stage, case–control study. Of the 25 SNPs in the DNMT-1 and DNMT-3B genes analyzed, only one (rs8101866) reached a normal significance level (P = 0.042). This association, however, was no longer statistically significant after adjustment for multiple comparisons. Our data suggest that there is no apparent association of common DNMT-1 and DNMT-3B polymorphisms with the risk of breast cancer among Chinese women.

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Fig. 1

Abbreviations

CI:

Confidence interval

DNMT:

DNA methyltransferase

htSNPs:

Haplotype tagging SNPs

HWE:

Hardy–Weinberg equilibrium

LD:

Linkage disequilibrium

MAF:

Minor allele frequency

QC:

Quality control

SNP:

Single nucleotide polymorphism

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Acknowledgments

We thank the participants and research staff of the Shanghai Breast Cancer Study for their contributions and commitment to this project, Regina Courtney and Qing Wang for laboratory assistance, and Bethanie Hull for her assistance in the preparation of this manuscript. Genotyping assays were conducted at the Vanderbilt Microarray Shared Resource and the Survey and Biospecimen Shared Resource; both are supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485).

Conflict of interest statement

The authors have no conflicts of interest to declare.

Financial support

This research was supported by National Cancer Institute grants R01 CA064277, R01 CA090899, and R01 CA122756.

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Authors and Affiliations

  1. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, B-2104, Medical Center North, 1161 21st Avenue South, Nashville, TN, 37232-2400, USA

    Chuanzhong Ye, Alicia Beeghly-Fadiel, Jirong Long, Xiao Ou Shu, Wei Zheng & Qiuyin Cai

  2. Shanghai Center for Disease Control and Prevention, Shanghai, China

    Wei Lu

  3. Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China

    Yu-Tang Gao

Authors
  1. Chuanzhong Ye
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  2. Alicia Beeghly-Fadiel
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  3. Wei Lu
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  4. Jirong Long
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  5. Xiao Ou Shu
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  6. Yu-Tang Gao
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  7. Wei Zheng
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  8. Qiuyin Cai
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Correspondence to Qiuyin Cai.

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Ye, C., Beeghly-Fadiel, A., Lu, W. et al. Two-stage case–control study of DNMT-1 and DNMT-3B gene variants and breast cancer risk. Breast Cancer Res Treat 121, 765–769 (2010). https://doi.org/10.1007/s10549-009-0569-9

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  • DOI: https://doi.org/10.1007/s10549-009-0569-9

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