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Association of common genetic variants with breast cancer risk and clinicopathological characteristics in a Chinese population

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations, and thus GWAS-identified single nucleotide polymorphisms (SNPs) in one population may not be of significance in another population. In order to explore the role of breast cancer susceptibility variants in a Chinese population of Southern Chinese descent, we analyzed 22 SNPs for 1,191 breast cancer cases and 1,534 female controls. Associations between the SNPs and clinicopathological features were also investigated. In addition, we evaluated the combined effects of associated SNPs by constructing risk models. Eight SNPs were associated with an elevated breast cancer risk. Rs2046210/6q25.1 increased breast cancer risk via an additive model [per-allele odds ratio (OR) = 1.43, 95 % confidence interval (CI) = 1.26–1.62], and was associated with estrogen receptor (ER)-positive (per-allele OR = 1.39, 95 % CI = 1.20–1.61) and ER-negative (per-allele OR = 1.55, 95 % CI = 1.28–1.89) disease. Rs2046210 was also associated with stage 1, stage 2, and stage 3 disease, with per-allele ORs of 1.38 (1.14–1.68), 1.48 (1.25–1.74), and 1.58 (1.28–1.94), respectively. Four SNPs mapped to 10q26.13/FGFR2 were associated with increased breast cancer risk via an additive model with per-allelic risks (95 % CI) of 1.26 (1.12–1.43) at rs1219648, 1.22 (1.07–1.38) at rs2981582, 1.21 (1.07–1.36) at rs2981579, and 1.18 (1.04–1.35) at rs11200014. Variants of rs7696175/TLR1, TLR6, rs13281615/8q24, and rs16886165/MAP3K1 were also associated with increased breast cancer risk, with per-allele ORs (95 % CI) of 1.16 (1.00–1.34), 1.15 (1.02–1.29), and 1.15 (1.01–1.29), respectively. Five SNPs associated with breast cancer risk predominantly among ER-positive tumors (rs2981582/FGFR2, rs4415084/MRPS30, rs1219648/FGFR2, rs2981579/FGFR2, and rs11200014/FGFR2). Among our Chinese population, the risk of developing breast cancer increased by 90 % for those with a combination of 6 or more risk alleles, compared to patients with ≤3 risk alleles.

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Abbreviations

CI:

Confidence interval

ER:

Estrogen receptor

GWAS:

Genome-wide association studies

HWE:

Hardy–Weinberg equilibrium

LD:

Linkage disequilibrium

MAF:

Minor allele frequency

OR:

Odds ratio

PR:

Progesterone receptor

SNP:

Single nucleotide polymorphisms

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Acknowledgments

This work was supported by a grant from the National Medical Research Council of Singapore (NMRC/1194/2008). We are also grateful to the staff of Singapore Institute for Clinical Sciences for the use of their BioMark equipment, and the SingHealth Tissue Repository for providing blood samples.

Conflict of interest

The authors declare no conflict of interest.

Ethical standards

The authors declare that the experiments comply with the current laws of Singapore in which they were performed.

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Correspondence to A. S. G. Lee.

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Chan, M., Ji, S.M., Liaw, C.S. et al. Association of common genetic variants with breast cancer risk and clinicopathological characteristics in a Chinese population. Breast Cancer Res Treat 136, 209–220 (2012). https://doi.org/10.1007/s10549-012-2234-y

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  • DOI: https://doi.org/10.1007/s10549-012-2234-y

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