Abstract
BackgroundGenome-wide association studies (GWAS) have identified several breast cancer susceptibility loci, and one genetic variant, rs11249433, at 1p11.2 was reported to be associated with breast cancer in European populations. To explore the genetic variants in this region associated with breast cancer in Chinese women, we conducted a two-stage fine-mapping study with a total of 1792 breast cancer cases and 1867 controls.Methodology/Principal FindingsSeven single nucleotide polymorphisms (SNPs) including rs11249433 in a 277 kb region at 1p11.2 were selected and genotyping was performed by using TaqMan® OpenArray™ Genotyping System for stage 1 samples (878 cases and 900 controls). In stage 2 (914 cases and 967 controls), three SNPs (rs2580520, rs4844616 and rs11249433) were further selected and genotyped for validation. The results showed that one SNP (rs2580520) located at a predicted enhancer region of SRGAP2 was consistently associated with a significantly increased risk of breast cancer in a recessive genetic model [Odds Ratio (OR) = 1.66, 95% confidence interval (CI) = 1.16–2.36 for stage 2 samples; OR = 1.51, 95% CI = 1.16–1.97 for combined samples, respectively]. However, no significant association was observed between rs11249433 and breast cancer risk in this Chinese population (dominant genetic model in combined samples: OR = 1.20, 95% CI = 0.92–1.57).Conclusions/SignificanceGenotypes of rs2580520 at 1p11.2 suggest that Chinese women may have different breast cancer susceptibility loci, which may contribute to the development of breast cancer in this population.
Highlights
Breast cancer is one of the most common cancers in the world and becoming the first cancer-related killer to the women
In stage 1, logistic regression analysis suggested that rs4844616 CT genotype had a 23% reduction of breast cancer risk (OR = 0.77, 95% confidence interval (CI) = 0.63–0.94, P = 0.011), while the combined rs4844616 CT/TT genotypes had a 18% reduction (OR = 0.82, 95% CI = 0.68–1.00, P = 0.045), when compared with the CC genotype
Rs2580520GG genotype was associated with a non-significant increased breast cancer risk in the recessive genetic model for stage 1 subjects (OR = 1.40, 95% CI = 0.93–2.09, P = 0.106)
Summary
Breast cancer is one of the most common cancers in the world and becoming the first cancer-related killer to the women. It was reported that the global burden of breast cancer in women was substantial and on the increase, with 1.38 million new cases diagnosed in 2008 [1,2]. A multistage genome-wide association study (GWAS) of breast cancer identified a new breast cancer susceptible locus at 1p11.2 (the marker SNP: rs11249433) in populations of European descent, which resides in a large linkage disequilibrium (LD) block neighboring NOTCH2 and FCGR1B [4]. Another combined analysis of GWAS in breast cancer reported the consistent result based on three GWAS of European descent [8]. To explore the genetic variants in this region associated with breast cancer in Chinese women, we conducted a two-stage finemapping study with a total of 1792 breast cancer cases and 1867 controls
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