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Associations of ATR and CHEK1 Single Nucleotide Polymorphisms with Breast Cancer

Overview of attention for article published in PLOS ONE, July 2013
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Title
Associations of ATR and CHEK1 Single Nucleotide Polymorphisms with Breast Cancer
Published in
PLOS ONE, July 2013
DOI 10.1371/journal.pone.0068578
Pubmed ID
Authors

Wei-Yu Lin, Ian W. Brock, Dan Connley, Helen Cramp, Rachel Tucker, Jon Slate, Malcolm W. R. Reed, Sabapathy P. Balasubramanian, Lisa A. Cannon-Albright, Nicola J. Camp, Angela Cox

Abstract

DNA damage and replication checkpoints mediated by the ATR-CHEK1 pathway are key to the maintenance of genome stability, and both ATR and CHEK1 have been proposed as potential breast cancer susceptibility genes. Many novel variants recently identified by the large resequencing projects have not yet been thoroughly tested in genome-wide association studies for breast cancer susceptibility. We therefore used a tagging SNP (tagSNP) approach based on recent SNP data available from the 1000 genomes projects, to investigate the roles of ATR and CHEK1 in breast cancer risk and survival. ATR and CHEK1 tagSNPs were genotyped in the Sheffield Breast Cancer Study (SBCS; 1011 cases and 1024 controls) using Illumina GoldenGate assays. Untyped SNPs were imputed using IMPUTE2, and associations between genotype and breast cancer risk and survival were evaluated using logistic and Cox proportional hazard regression models respectively on a per allele basis. Significant associations were further examined in a meta-analysis of published data or confirmed in the Utah Breast Cancer Study (UBCS). The most significant associations for breast cancer risk in SBCS came from rs6805118 in ATR (p=7.6 x 10(-5)) and rs2155388 in CHEK1 (p=3.1 x 10(-6)), but neither remained significant after meta-analysis with other studies. However, meta-analysis of published data revealed a weak association between the ATR SNP rs1802904 (minor allele frequency is 12%) and breast cancer risk, with a summary odds ratio (confidence interval) of 0.90 (0.83-0.98) [p=0.0185] for the minor allele. Further replication of this SNP in larger studies is warranted since it is located in the target region of 2 microRNAs. No evidence of any survival effects of ATR or CHEK1 SNPs were identified. We conclude that common alleles of ATR and CHEK1 are not implicated in breast cancer risk or survival, but we cannot exclude effects of rare alleles and of common alleles with very small effect sizes.

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The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 26 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 19%
Researcher 5 19%
Other 3 12%
Student > Master 3 12%
Professor 2 8%
Other 6 23%
Unknown 2 8%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 31%
Biochemistry, Genetics and Molecular Biology 6 23%
Medicine and Dentistry 6 23%
Social Sciences 2 8%
Unknown 4 15%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 February 2014.
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#18,369,403
of 22,751,628 outputs
Outputs from PLOS ONE
#154,398
of 194,172 outputs
Outputs of similar age
#145,954
of 194,389 outputs
Outputs of similar age from PLOS ONE
#3,637
of 4,780 outputs
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