Tumor Biology

, Volume 37, Issue 7, pp 9739–9744 | Cite as

Relationship between five GWAS-identified single nucleotide polymorphisms and female breast cancer in the Chinese Han population

  • Yaning He
  • Hui Liu
  • Qi Chen
  • Xianfu Sun
  • Chaojun Liu
  • Yingbo Shao
Original Article

Abstract

With the development of genome-wide association study (GWAS), an increasing number of genetic variables have been confirmed to be associated with breast cancer. Furthermore, an increasing number of studies from Asian populations are becoming available. Few GWAS loci have been replicated in the Chinese Han population. In a case–control study of breast cancer in the Henan Tumor Hospital (253 cases/339 controls), we evaluated five SNPs from GWAS of populations of European or Asian ancestry. In order to evaluate the contribution of genetic factors to population differences in breast cancer subtypes, all cases are defined by estrogen (ER), progesterone (PR) receptor, Human epidermal growth factor receptor - 2 (HER2), and Ki67 status. Different genotypes of rs3803662 (TOX3)/ (TNRC9)) in the case group and the control group are statistically significant (P = 0.044), but the ones of rs10069690 (TERT), rs2046210 (6q25.1), rs2981582 (EGFR2), and rs889312 (MAP3K1) have no significant statistical differences with breast cancer (P = 0.772, 0.308, 0.376, 0.468). The allelic frequencies of rs3803662 between the case group and the control group differ in recessive genetic models (odds ratio (OR) = 2.04, 95 % confidence interval (CI) 1.14–3.66) and in con-dominant inheritance models (OR = 2.17, 95 % CI 1.18–4.00). Compared with AA and GA, GG increased the risk of breast cancer (P = 0.017, 0.013). The genotype of rs2046210 (6q25.1), rs2981582 (EGFR2), rs889312 (MAP3K1), and rs3803662 (TOX3/TNRC9) has no statistical differences in different subtypes of breast cancer. Five common breast cancer susceptibility loci from GWAS are not strongly associated with breast cancer risk among the Han Chinese of the Henan province; only rs3803662 (TOX3/TNRC9) is confirmed to increase the risk of breast cancer. The different genotypes of five loci distribute equally in different subtypes of breast cancer.

Keywords

Breast cancer Subtypes of breast cancer SNPs GWAS 

Notes

Acknowledgments

We thank all subjects for providing the DNA and information necessary for our study. We also thank Central Laboratory of Henan Tumor Hospital and Shanghai Genesky Bio-Tech Co., Ltd. (http://biotech.geneskies.com/index.html), for valuable help with the isolation of DNA and the test of SNPs.

Compliance with ethical standards

Conflicts of interest

None

References

  1. 1.
    Esther MJ, Hopper JL, Beck JC, et al. The breast cancer family registry: an infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer. Breast Cancer Res. 2004;6:R375–89.CrossRefGoogle Scholar
  2. 2.
    Long J, Delahanty RJ, Li G. A common deletion in the APOBEC3 genes and breast cancer risk. J Natl Cancer Inst. 2013;14.Google Scholar
  3. 3.
    Easton DF, Pooley KA, Dunning AM, et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature. 2007;447:1087–93.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Gold B, Kirchhoff T, Stefanov S, et al. Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33. Proc Natl Acad Sci U S A. 2008;105:4340–5.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Stacey SN, Manolescu A, Sulem P, et al. Common variants on chromosome 5p12 confer usceptibility to estrogen receptor-positive breast cancer. Nat Genet. 2008;40:703–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Zheng W, Long J, Gao YT, et al. Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nat Genet. 2009;41:324–8.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Stacey SN, Manolescu A, Sulem P, et al. Common variants on chromosomes 2q35 nd 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet. 2007;39:865–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Garcia-Closas M, Hall P, Nevanlinna H, et al. Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. PLoS Genet. 2008;4, e1000054.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Han W, Woo JH, Yu J-H, et al. Common genetic variants associated with breast cancer in Korean women and differential susceptibility according to intrinsic subtype. Cancer Epidemiol Biomarkers Prev. 2011;20:793–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Mulligan AM, Couch FJ, Barrowdale D, et al. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the consortium of investigators of modifiers of BRCA1/2. Breast Cancer Res. 2011;13:R110.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Dai J, Hu Z, Yue Y, et al. Breast cancer risk assessment with five independent genetic variants and two risk factors in Chinese women. Breast Cancer Res. 2012;14:R17.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Hein R, Maranian M, et al. Comparison of 6q25 breast cancer hits from Asian an European Genome Wide Association studies in the Breast Cancer Association Consortium (BCAC). Plos One. 2012;7(8), e42380.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Palmer JR, Ruiz-Narvaez EA, Rotimi CN, et al. Genetic susceptibility loci for subtypes of breast cancer in an African American population. Cancer Epidemiol Biomarkers Prev. 2013;22:127–34.CrossRefPubMedGoogle Scholar
  14. 14.
    Chen W, Zheng R, Zhang S, et al. The incidences and mortalities of major cancers in China, 2009. Chin J Cancer. 2013;32(3):106–12.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Pharoah PD, Antoniou AC, Easton DF, et al. Polygenes, risk prediction, and targeted prevention of breast cancer. N Engl J Med. 2008;358:2796–803.CrossRefPubMedGoogle Scholar
  16. 16.
    Gail MH. Personalized estimates of breast cancer risk in clinical practice and public health. Stat Med. 2011;30:1090–104.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Yu KD, Fang Q, Shao ZM. Combining accurate genetic and clinical information in breast cancer risk model. Breast Cancer Res Treat. 2011;128:283–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Hartman M, Suo C, Lim WY, et al. Ability to predict breast cancer in Asian women using a polygenic susceptibility model. Breast Cancer Res Treat. 2011;127:805–12.CrossRefPubMedGoogle Scholar
  19. 19.
    Wacholder S, Hartge P, Prentice R, et al. Performance of common genetic variants in breast-cancer risk models. N Engl J Med. 2010;362:986–93.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gail MH, Mai PL. Comparing breast cancer risk assessment models. J Natl Cancer Inst. 2010;102:665–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Zheng W, Wen W, Gao YT, et al. Genetic and clinical predictors for breast cancer risk assessment and stratification among Chinese women. J Natl Cancer Inst. 2010;102:972–81.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Stevens KN, Vachon CM, Lee AM, et al. Common breast cancer susceptibility loci are associated with triple negative breast cancer. Cancer Res. 2011;71(19):6240–9. doi: 10.1158/0008-5472.CAN-11-1266.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Gudmundsdottir ET, Barkardottir RB, Adalgeir A, et al. The risk allele of SNP rs3803662 and the mRNA level of its closest genes TOX3 and LOC643714 predict adverse outcome for breast cancer patients. BMC Cancer. 2012;12:621.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Xi W, Qing-Qing X, Liang G, et al. Quantitative Assessment of the Association between rs2046210 at 6q25. 1 and breast cancer risk. PLoS ONE. 2013;8(6), e65206.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Yaning He
    • 1
  • Hui Liu
    • 1
  • Qi Chen
    • 1
  • Xianfu Sun
    • 1
  • Chaojun Liu
    • 1
  • Yingbo Shao
    • 1
  1. 1.Department of Breast SurgeryAffiliated Tumor Hospital of Zhengzhou University (Henan Tumor Hospital)ZhengzhouChina

Personalised recommendations