Skip to main content
Log in

Association of polymorphisms in intron 2 of FGFR2 and breast cancer risk in Chinese women

  • Published:
Cytology and Genetics Aims and scope Submit manuscript

Abstract

Recent genome-wide association studies (GWAS) demonstrated that genetic variation in intron 2 of fibroblast growth factor receptor 2 (FGFR2) was a novel risk for breast cancer. We investigated whether two SNPs rs1219648 and rs2981582 in intron 2 of FGFR2 were associated with the risk of breast cancer in Chinese women. A total of 340 female breast cancer patients and 400 normal age-matched controls were recruited. Two SNPs were genotyped using matrix-assisted laser desorption/ionization mass spectrometry. The two SNPs rs1219648 and rs2981582 showed no association with the risk of breast cancer. A subgroup analysis by menopausal status demonstrated that the distribution of rs2981582 T alleles, including CT and TT genotypes, was significantly higher in premenopausal patients compared with postmenopausal patients. The TT genotype in rs2981582 was more strongly associated with ER-positive than with ER-negative tumors by ER status analysis. Analysis by haplotypes showed that no haplotypes associated with breast cancer. The results showed no association between two SNPs, rs1219648 and rs2981582 and breast cancer risk, although in a stratified analysis rs2981582 strongly associated with premenopausal and ER-positive breast cancer patients in Chinese women.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Jemal, A., Sieger, R., Ward, E., Hao, Y., Xu, J., and Thun, M.J., Cancer statistics 2009, CA Cancer J. Clin., 2009, vol. 59, no. 4, pp. 225–249.

    Article  PubMed  Google Scholar 

  2. Pharoah, P.D., Dunning, A.M., Ponder, B.A., and Easton, D.F., Association studies for finding cancersusceptibility genetic variants, Nat. Rev. Cancer, 2004, vol. 4, no. 11, pp. 850–860.

    Article  PubMed  CAS  Google Scholar 

  3. Katoh, Y. and Katoh, M., FGFR2-related pathogenesis and FGFR2-targeted therapeutics (review), Int. J. Mol. Med., 2009, vol. 23, no. 3, pp. 307–311.

    Article  PubMed  CAS  Google Scholar 

  4. Davies, H., Hunter, C., Smith, R., et al., Somatic mutations of the protein kinase gene family in human lung cancer, Cancer Res., 2005, vol. 65, no. 17, pp. 7591–7595.

    PubMed  CAS  Google Scholar 

  5. Jang, J.H., Shin, K.H., and Park, J.G., Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers, Cancer Res., 2001, vol. 61, no. 9, pp. 3541–3543.

    PubMed  CAS  Google Scholar 

  6. Udler, M.S., Meyer, K.B., Pooley, K.A., et al., FGFR2 variants and breast cancer risk: fine-scale mapping using African American studies and analysis of chromatin conformation, Hum. Mol. Genet., 2009, vol. 18, no. 9, pp. 1692–1703.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Hunter, D.J., Kraft, P., Jacobs, K.B., et al., A genomewide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer, Nat. Genet., 2007, vol. 39, no. 7, pp. 870–874.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Raskin, L., Pinchev, M., Arad, C., et al., FGFR2 is a breast cancer susceptibility gene in Jewish and Arab Israeli populations, Cancer Epidemiol. Biomarkers Prev., 2005, vol. 17, no. 5, pp. 1060–1065.

    Article  Google Scholar 

  9. Easton, D.F., Pooley, K.A., Dunning, A.M., et al., Genome-wide association study identifies novel breast cancer susceptibility loci, Nature, 2007, vol. 447, no. 7148, pp. 1087–1093.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Jia, C., Cai, Y., Ma, Y., and Fu, D., Quantitative assessment of the effect of FGFR2 gene polymorphism on the risk of breast cancer, Breast Cancer Res. Treat., 2010, vol. 124, no. 2, pp. 521–528.

    Article  PubMed  CAS  Google Scholar 

  11. Zhang, J., Qiu, L.X., Wang, Z.H., et al., Current evidence on the relationship between three polymorphisms in the FGFR2 gene and breast cancer risk: a meta-analysis, Breast Cancer Res., pp. 419–424.

  12. Chen, X.H., Li, X.Q., Chen, Y., and Feng, Y.M., Risk of aggressive breast cancer in women of Han nationality carrying TGFB1 rs1982073 C allele and FGFR2 rs1219648 G allele in North China, Breast Cancer Res. Treat., 2011, vol. 125, no. 2, pp. 575–582.

    Article  PubMed  CAS  Google Scholar 

  13. Liu, C.L., Hu, X.P., Guo, W.D., Yang, L., Dang, J., and Jiao, H.Y., Case-control study on the fibroblast growth factor receptor 2 gene polymorphisms associated with breast cancer in Chinese Han women, J. Breast Cancer, 2013, vol. 16, no. 4, pp. 366–371.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Long, J., Shu, X.O., Cai, Q., et al., Evaluation of breast cancer susceptibility loci in Chinese women, Cancer Epidemiol. Biomarkers Prev., 2010, vol. 19, pp. 2357–2365.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Liang, J., Chen, P., Hu, Z., et al., Genetic variants in fibroblast growth factor receptor 2 (FGFR2) contribute to susceptibility of breast cancer in Chinese women, Carcinogenesis, 2008, vol. 29, no. 12, pp. 2341–2346.

    Article  PubMed  CAS  Google Scholar 

  16. Fu, F., Wang, C., Huang, M., Song, C., Lin, S., and Huang, H., Polymorphisms in second intron of the FGFR2 gene are associated with the risk of early-onset breast cancer in Chinese Han women, Tohoku J. Exp. Med., vol. 226, no. 3, pp. 221–229.

  17. 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, vol. 4, no. 4, e1000054.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Slattery, M.L., John, E.M., Stern, M.C., et al., Associations with growth factor genes (FGF1, FGF2, PDGFB, FGFR2, NRG2, EGF, ERBB2) with breast cancer risk and survival: the Breast Cancer Health Disparities Study, Breast Cancer Res. Treat., 2013, vol. 140, no. 3, pp. 587–601.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Cen, Y.L., Qi, M.L., Li, H.G., et al., Associations of polymorphisms in the genes of FGFR2, FGF1, and RBFOX2 with breast cancer risk by estrogen/progesterone receptor status, Mol. Carcinog., 2013, vol. 52, Suppl. 1, pp. E52–E59.

    Article  PubMed  CAS  Google Scholar 

  20. Chan, M., Ji, S.M., Liaw, C.S., et al., Association of common genetic variants with breast cancer risk and clinocopathological characteristics in a Chinese population, Breast Cancer Res. Treat., 2012, vol. 136, no. 1, pp. 209–220.

    Article  PubMed  CAS  Google Scholar 

  21. Tapper, W., Hammond, V., Gerty, S., et al., The influence of genetic variation in 30 selected genes on the clinical characteristics of early onset breast cancer, Breast Cancer Res., 2008, vol. 10, no. 6, p. R108.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Campa, D., Kaaks, R., Le Marchand, L., et al., Interactions between genetic variants and breast cancer risk factors in the breast and prostate cancer cohort consortium, J. Natl. Cancer Inst., 2011, vol. 103, no. 16, pp. 1252–1263.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kawase, T., Matsuo, K., Suzuki, T., Hiraki, A., Watanabe, M., Iwata, H., Tanaka, H., and Tajima, K., FGFR2 intronic polymorphisms interact with reproductive risk factors of breast cancer: results of a case control study in Japan, Int. J. Cancer, 2009, vol. 125, no. 8, pp. 1946–1952.

    Article  PubMed  CAS  Google Scholar 

  24. Jurinke, C., van den Boom, D., Cantor, C.R., and Koster, H., Automated genotyping using the DNA MassArray technology, Methods Mol. Biol., 2002, vol. 187, pp. 179–192.

    PubMed  CAS  Google Scholar 

  25. Sole, X., Guino, E., Valls, J., Iniesta, R., and Moreno, V., SNPStats: a web tool for the analysis of association studies, Bioinformatics, 2006, vol. 22, no. 15, pp. 1928–1929.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to X. Xu.

Additional information

The article is published in the original.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pan, Z., Bao, Y., Zheng, X. et al. Association of polymorphisms in intron 2 of FGFR2 and breast cancer risk in Chinese women. Cytol. Genet. 50, 312–317 (2016). https://doi.org/10.3103/S009545271605008X

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S009545271605008X

Keywords

Navigation