A Common Deletion in the APOBEC3 Genes and Breast Cancer Risk (original) (raw)

Journal Article

,

Affiliations of authors:

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center

(JL, RJD, GL, QC, X-OS, WZ) and

Department of Biostatistics

(CL),

Vanderbilt University School of Medicine, Nashville

,

TN

;

Shanghai Center for Disease Control and Prevention

,

Shanghai, China

(WL, YZ);

Department of Epidemiology, Shanghai Cancer Institute

,

Shanghai, China

(Y-TG, Y-BX);

Division of Cancer Epidemiology and Genetics, National Cancer Institute

,

Bethesda, Maryland

(B-TJ);

Department of Surgery & Cancer, Imperial College London

,

London

, UK (SA).

Search for other works by this author on:

,

Affiliations of authors:

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center

(JL, RJD, GL, QC, X-OS, WZ) and

Department of Biostatistics

(CL),

Vanderbilt University School of Medicine, Nashville

,

TN

;

Shanghai Center for Disease Control and Prevention

,

Shanghai, China

(WL, YZ);

Department of Epidemiology, Shanghai Cancer Institute

,

Shanghai, China

(Y-TG, Y-BX);

Division of Cancer Epidemiology and Genetics, National Cancer Institute

,

Bethesda, Maryland

(B-TJ);

Department of Surgery & Cancer, Imperial College London

,

London

, UK (SA).

Search for other works by this author on:

,

Affiliations of authors:

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center

(JL, RJD, GL, QC, X-OS, WZ) and

Department of Biostatistics

(CL),

Vanderbilt University School of Medicine, Nashville

,

TN

;

Shanghai Center for Disease Control and Prevention

,

Shanghai, China

(WL, YZ);

Department of Epidemiology, Shanghai Cancer Institute

,

Shanghai, China

(Y-TG, Y-BX);

Division of Cancer Epidemiology and Genetics, National Cancer Institute

,

Bethesda, Maryland

(B-TJ);

Department of Surgery & Cancer, Imperial College London

,

London

, UK (SA).

Search for other works by this author on:

,

Affiliations of authors:

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center

(JL, RJD, GL, QC, X-OS, WZ) and

Department of Biostatistics

(CL),

Vanderbilt University School of Medicine, Nashville

,

TN

;

Shanghai Center for Disease Control and Prevention

,

Shanghai, China

(WL, YZ);

Department of Epidemiology, Shanghai Cancer Institute

,

Shanghai, China

(Y-TG, Y-BX);

Division of Cancer Epidemiology and Genetics, National Cancer Institute

,

Bethesda, Maryland

(B-TJ);

Department of Surgery & Cancer, Imperial College London

,

London

, UK (SA).

Search for other works by this author on:

,

Affiliations of authors:

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center

(JL, RJD, GL, QC, X-OS, WZ) and

Department of Biostatistics

(CL),

Vanderbilt University School of Medicine, Nashville

,

TN

;

Shanghai Center for Disease Control and Prevention

,

Shanghai, China

(WL, YZ);

Department of Epidemiology, Shanghai Cancer Institute

,

Shanghai, China

(Y-TG, Y-BX);

Division of Cancer Epidemiology and Genetics, National Cancer Institute

,

Bethesda, Maryland

(B-TJ);

Department of Surgery & Cancer, Imperial College London

,

London

, UK (SA).

Search for other works by this author on:

,

Affiliations of authors:

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center

(JL, RJD, GL, QC, X-OS, WZ) and

Department of Biostatistics

(CL),

Vanderbilt University School of Medicine, Nashville

,

TN

;

Shanghai Center for Disease Control and Prevention

,

Shanghai, China

(WL, YZ);

Department of Epidemiology, Shanghai Cancer Institute

,

Shanghai, China

(Y-TG, Y-BX);

Division of Cancer Epidemiology and Genetics, National Cancer Institute

,

Bethesda, Maryland

(B-TJ);

Department of Surgery & Cancer, Imperial College London

,

London

, UK (SA).

Search for other works by this author on:

,

Affiliations of authors:

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center

(JL, RJD, GL, QC, X-OS, WZ) and

Department of Biostatistics

(CL),

Vanderbilt University School of Medicine, Nashville

,

TN

;

Shanghai Center for Disease Control and Prevention

,

Shanghai, China

(WL, YZ);

Department of Epidemiology, Shanghai Cancer Institute

,

Shanghai, China

(Y-TG, Y-BX);

Division of Cancer Epidemiology and Genetics, National Cancer Institute

,

Bethesda, Maryland

(B-TJ);

Department of Surgery & Cancer, Imperial College London

,

London

, UK (SA).

Search for other works by this author on:

,

Affiliations of authors:

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center

(JL, RJD, GL, QC, X-OS, WZ) and

Department of Biostatistics

(CL),

Vanderbilt University School of Medicine, Nashville

,

TN

;

Shanghai Center for Disease Control and Prevention

,

Shanghai, China

(WL, YZ);

Department of Epidemiology, Shanghai Cancer Institute

,

Shanghai, China

(Y-TG, Y-BX);

Division of Cancer Epidemiology and Genetics, National Cancer Institute

,

Bethesda, Maryland

(B-TJ);

Department of Surgery & Cancer, Imperial College London

,

London

, UK (SA).

Search for other works by this author on:

,

Affiliations of authors:

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center

(JL, RJD, GL, QC, X-OS, WZ) and

Department of Biostatistics

(CL),

Vanderbilt University School of Medicine, Nashville

,

TN

;

Shanghai Center for Disease Control and Prevention

,

Shanghai, China

(WL, YZ);

Department of Epidemiology, Shanghai Cancer Institute

,

Shanghai, China

(Y-TG, Y-BX);

Division of Cancer Epidemiology and Genetics, National Cancer Institute

,

Bethesda, Maryland

(B-TJ);

Department of Surgery & Cancer, Imperial College London

,

London

, UK (SA).

Search for other works by this author on:

,

Affiliations of authors:

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center

(JL, RJD, GL, QC, X-OS, WZ) and

Department of Biostatistics

(CL),

Vanderbilt University School of Medicine, Nashville

,

TN

;

Shanghai Center for Disease Control and Prevention

,

Shanghai, China

(WL, YZ);

Department of Epidemiology, Shanghai Cancer Institute

,

Shanghai, China

(Y-TG, Y-BX);

Division of Cancer Epidemiology and Genetics, National Cancer Institute

,

Bethesda, Maryland

(B-TJ);

Department of Surgery & Cancer, Imperial College London

,

London

, UK (SA).

Search for other works by this author on:

... Show more

Received:

04 September 2012

Revision received:

20 December 2012

Accepted:

21 December 2012

Published:

14 February 2013

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Jirong Long, Ryan J. Delahanty, Guoliang Li, Yu-Tang Gao, Wei Lu, Qiuyin Cai, Yong-Bing Xiang, Chun Li, Bu-Tian Ji, Ying Zheng, Simak Ali, Xiao-Ou Shu, Wei Zheng, A Common Deletion in the APOBEC3 Genes and Breast Cancer Risk, JNCI: Journal of the National Cancer Institute, Volume 105, Issue 8, 17 April 2013, Pages 573–579, https://doi.org/10.1093/jnci/djt018
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Abstract

Background

Genome-wide association studies (GWASs) have identified multiple genetic susceptibility loci for breast cancer. However, these loci explain only a small fraction of the heritability. Very few studies have evaluated copy number variation (CNV), another important source of human genetic variation, in relation to breast cancer risk.

Methods

We conducted a CNV GWAS in 2623 breast cancer patients and 1946 control subjects using data from Affymetrix SNP Array 6.0 (stage 1). We then replicated the most promising CNV using real-time quantitative polymerase chain reaction (qPCR) in an independent set of 4254 case patients and 4387 control subjects (stage 2). All subjects were recruited from population-based studies conducted among Chinese women in Shanghai.

Results

Of the 268 common CNVs (minor allele frequency ≥ 5%) investigated in stage 1, the strongest association was found for a common deletion in the APOBEC3 genes (P = 1.1×10−4) and was replicated in stage 2 (odds ratio =1.35, 95% confidence interval [CI] = 1.27 to 1.44; P = 9.6×10−22). Analyses of all samples from both stages using qPCR data produced odds ratios of 1.31 (95% CI = 1.21 to 1.42) for a one-copy deletion and 1.76 (95% CI = 1.57 to 1.97) for a two-copy deletion (P = 2.0×10−24).

Conclusions

We provide convincing evidence for a novel breast cancer locus at the APOBEC3 genes. This CNV is one of the strongest common genetic risk variants identified so far for breast cancer.

© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Topic:

• gene frequency
• genes
• genetic predisposition to disease
• single nucleotide polymorphism
• genetics
• breast cancer
• genetic risk
• genotype determination
• ecological study
• genome-wide association study
• quantitative real-time polymerase chain reaction
• breast cancer risk
• copy number polymorphism

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