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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=7.6x10 -5 ) and rs2155388 in  CHEK1  (p=3.1x10 -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.

Associations of ATR and CHEK1 Single Nucleotide Polymorphisms with Breast Cancer