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Risk of genome-wide association study newly identified genetic variants for breast cancer in Chinese women of Heilongjiang Province

  • Epidemiology
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Abstract

Recent genome-wide association studies have identified seven single nucleotide polymorphisms (SNPs) associated with breast cancer, but mainly in Europeans. In this study, the authors evaluated the effect of these loci on breast cancer and its disease characteristics in women from northeast of China, Heilongjiang Province. Seven SNPs were successfully genotyped in 492 breast cancer patients and 510 healthy controls using the SNaPshot method. The associations between SNPs and breast cancer were examined by logistic regression. The associations between SNPs and disease characteristics were examined by the chi-square test or one-way ANOVA as needed. The authors confirmed the effects of the allele A for rs2046210 at 6q25 on increased breast cancer risk in the population, with odds ratio 1.417 (P = 2×10−4). However, no significant association was detected between SNPs from TNCR9, LSP1, MAP3K1, 2q35, and 8q24 and breast cancer. Analyses of the disease characteristics showed that SNP rs2046210 was associated with age at menopause (P = 0.001). MAP3K1 SNP rs889312 and LSP1 SNP rs3817198 were associated with HER2 status in the patient cohort (P = 0.036 and P = 0.005, respectively). And SNP rs3817198 was also associated with the combined status of estrogen receptor, progesterone receptor, and HER2 (P = 0.012). SNP rs13281615 was associated with age at menarche (P = 0.023), and SNP rs3803662 was associated with average duration of breastfeeding (P = 0.036). All other disease characteristics, including tumor grade, clinical stage, and the status of estrogen receptor or P53, were not significantly associated with any of these variants. These results suggested that the rs2046210 was associated with breast cancer in a Northern Chinese population, and some SNPs were also associated with breast cancer characteristics.

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References

  1. Yang L, Parkin DM, Ferlay J, Li L, Chen Y (2005) Estimates of cancer incidence in China for 2000 and projections for 2005. Cancer Epidemiol Biomarkers Prev 14(1):243–250

    PubMed  Google Scholar 

  2. Kelsey JL, Gammon MD (1991) The epidemiology of breast cancer. CA Cancer J Clin 41(3):146–165

    Article  PubMed  CAS  Google Scholar 

  3. McPherson K, Steel CM, Dixon JM (2000) ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ 321(7261):624–628

    Article  PubMed  CAS  Google Scholar 

  4. Bray F, McCarron P, Parkin DM (2004) The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res 6(6):229–239

    Article  PubMed  Google Scholar 

  5. Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, Easton DF, Evans C, Deacon J, Stratton MR (1999) Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 91(11):943–949

    Article  PubMed  CAS  Google Scholar 

  6. Pharoah PD, Dunning AM, Ponder BA, Easton DF (2004) Association studies for finding cancer-susceptibility genetic variants. Nat Rev Cancer 4(11):850–860

    Article  PubMed  CAS  Google Scholar 

  7. Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R, Wareham N, Ahmed S et al (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447(7148):1087–1093

    Article  PubMed  CAS  Google Scholar 

  8. Stacey SN, Manolescu A, Sulem P, Rafnar T, Gudmundsson J, Gudjonsson SA, Masson G, Jakobsdottir M, Thorlacius S, Helgason A, Aben KK, Strobbe LJ et al (2007) Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 39(7):865–869

    Article  PubMed  CAS  Google Scholar 

  9. Zheng W, Long J, Gao YT, Li C, Zheng Y, Xiang YB, Wen W, Levy S, Deming SL, Haines JL, Gu K, Fair AM et al (2009) Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nat Genet 41(3):324–328

    Article  PubMed  CAS  Google Scholar 

  10. Yeager M, Orr N, Hayes RB, Jacobs KB, Kraft P, Wacholder S, Minichiello MJ, Fearnhead P, Yu K, Chatterjee N, Wang Z, Welch R et al (2007) Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet 39(5):645–649

    Article  PubMed  CAS  Google Scholar 

  11. Haiman CA, Patterson N, Freedman ML, Myers SR, Pike MC, Waliszewska A, Neubauer J, Tandon A, Schirmer C, McDonald GJ, Greenway SC, Stram DO et al (2007) Multiple regions within 8q24 independently affect risk for prostate cancer. Nat Genet 39(5):638–644

    Article  PubMed  CAS  Google Scholar 

  12. Zanke BW, Greenwood CM, Rangrej J, Kustra R, Tenesa A, Farrington SM, Prendergast J, Olschwang S, Chiang T, Crowdy E, Ferretti V, Laflamme P et al (2007) Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat Genet 39(8):989–994

    Article  PubMed  CAS  Google Scholar 

  13. Haiman CA, Le Marchand L, Yamamato J, Stram DO, Sheng X, Kolonel LN, Wu AH, Reich D, Henderson BE (2007) A common genetic risk factor for colorectal and prostate cancer. Nat Genet 39(8):954–956

    Article  PubMed  CAS  Google Scholar 

  14. Tomlinson I, Webb E, Carvajal-Carmona L, Broderick P, Kemp Z, Spain S, Penegar S, Chandler I, Gorman M, Wood W, Barclay E, Lubbe S et al (2007) A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet 39(8):984–988

    Article  PubMed  CAS  Google Scholar 

  15. Gruber SB, Moreno V, Rozek LS, Rennerts HS, Lejbkowicz F, Bonner JD, Greenson JK, Giordano TJ, Fearson ER, Rennert G (2007) Genetic variation in 8q24 associated with risk of colorectal cancer. Cancer Biol Ther 6(7):1143–1147

    Article  PubMed  CAS  Google Scholar 

  16. Smid M, Wang Y, Klijn JG, Sieuwerts AM, Zhang Y, Atkins D, Martens JW, Foekens JA (2006) Genes associated with breast cancer metastatic to bone. J Clin Oncol 24(15):2261–2267

    Article  PubMed  CAS  Google Scholar 

  17. Huijts PE, Vreeswijk MP, Kroeze-Jansema KH, Jacobi CE, Seynaeve C, Krol-Warmerdam EM, Wijers-Koster PM, Blom JC, Pooley KA, Klijn JG, Tollenaar RA, Devilee P, van Asperen CJ (2007) Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases. Breast Cancer Res 9(6):R78

    Article  PubMed  Google Scholar 

  18. Jakobsson M, Scholz SW, Scheet P, Gibbs JR, Van Liere JM, Fung HC, Szpiech ZA, Degnan JH, Wang K, Guerreiro R, Bras JM, Schymick JC et al (2008) Genotype, haplotype and copy-number variation in worldwide human populations. Nature 451(7181):998–1003

    Article  PubMed  CAS  Google Scholar 

  19. Xu S, Yin X, Li S, Jin W, Lou H, Yang L, Gong X, Wang H, Shen Y, Pan X, He Y, Yang Y et al (2009) Genomic dissection of population substructure of Han Chinese and its implication in association studies. Am J Hum Genet 85(6):762–774

    Article  PubMed  CAS  Google Scholar 

  20. Turnbull C, Ahmed S, Morrison J, Pernet D, Renwick A, Maranian M, Seal S, Ghoussaini M, Hines S, Healey CS, Hughes D, Warren-Perry M et al (2010) Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet 42(6):504–507

    Article  PubMed  CAS  Google Scholar 

  21. Garcia-Closas M, Hall P, Nevanlinna H, Pooley K, Morrison J, Richesson DA, Bojesen SE, Nordestgaard BG, Axelsson CK, Arias JI, Milne RL, Ribas G et al (2008) Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. PLoS Genet 4(4):e1000054

    Article  PubMed  Google Scholar 

  22. Zheng W, Wen W, Gao YT, Shyr Y, Zheng Y, Long J, Li G, Li C, Gu K, Cai Q, Shu XO, Lu W (2010) Genetic and clinical predictors for breast cancer risk assessment and stratification among Chinese women. J Natl Cancer Inst 102(13):972–981

    Article  PubMed  CAS  Google Scholar 

  23. Woolcott CG, Maskarinec G, Haiman CA, Verheus M, Pagano IS, Le Marchand L, Henderson BE, Kolonel LN (2009) Association between breast cancer susceptibility loci and mammographic density: the Multiethnic Cohort. Breast Cancer Res 11(1):R10

    Article  PubMed  Google Scholar 

  24. Rebbeck TR, DeMichele A, Tran TV, Panossian S, Bunin GR, Troxel AB, Strom BL (2009) Hormone-dependent effects of FGFR2 and MAP3K1 in breast cancer susceptibility in a population-based sample of post-menopausal African-American and European-American women. Carcinogenesis 30(2):269–274

    Article  PubMed  CAS  Google Scholar 

  25. Stendahl M, Ryden L, Nordenskjold B, Jonsson PE, Landberg G, Jirstrom K (2006) High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients. Clin Cancer Res 12(15):4614–4618

    Article  PubMed  CAS  Google Scholar 

  26. Ladjemi MZ, Jacot W, Chardes T, Pelegrin A, Navarro-Teulon I (2010) Anti-HER2 vaccines: new prospects for breast cancer therapy. Cancer Immunol Immunother 59(9):1295–1312

    Article  PubMed  CAS  Google Scholar 

  27. Beenken SW, Grizzle WE, Crowe DR, Conner MG, Weiss HL, Sellers MT, Krontiras H, Urist MM, Bland KI (2001) Molecular biomarkers for breast cancer prognosis: coexpression of c-erbB-2 and p53. Ann Surg 233(5):630–638

    Article  PubMed  CAS  Google Scholar 

  28. Shimizu C, Fukutomi T, Tsuda H, Akashi-Tanaka S, Watanabe T, Nanasawa T, Sugihara K (2000) c-erbB-2 protein overexpression and p53 immunoreaction in primary and recurrent breast cancer tissues. J Surg Oncol 73(1):17–20

    Article  PubMed  CAS  Google Scholar 

  29. Logullo AF, Lopes AB, Nonogaki S, Soares FA, Netto MM, Nishimoto IN, Brentani MM (2007) C-erbB-2 expression is a better predictor for survival than galectin-3 or p53 in early-stage breast cancer. Oncol Rep 18(1):121–126

    PubMed  Google Scholar 

  30. de Azambuja E, Cardoso F, de Castro G, Jr ColozzaM, Mano MS, Durbecq V, Sotiriou C, Larsimont D, Piccart-Gebhart MJ, Paesmans M (2007) Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer 96(10):1504–1513

    Article  PubMed  Google Scholar 

  31. Viale G, Regan MM, Mastropasqua MG, Maffini F, Maiorano E, Colleoni M, Price KN, Golouh R, Perin T, Brown RW, Kovacs A, Pillay K et al (2008) Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst 100(3):207–212

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Yongdong Jiang performed the primer design and wrote the drafts. Jiguang Han, Jing Liu, Guoqiang Zhang, Lihong Wang, and Feng Liu collected the patient and control blood samples and performed the SNaPshot SNP assay. Xianyu Zhang contributed statistical analysis. Yashuang Zhao and Da Pang conceived of the study, and participated in its design and coordination, and helped to draft the article. All authors read and approved the final manuscript. This study was supported by the Key Science and Technology Program of Heilongjiang Province, China (Da Pang, Grant no. GC08C501), Fund of Heilongjiang Provincial Finance Department (Da Pang, Grant no. 2009-06). The authors thank all patients and healthy volunteers for providing blood samples and all the research staff for their contributions to this project.

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The authors declare that they have no conflicts of interest.

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Correspondence to Yashuang Zhao or Da Pang.

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Yongdong Jiang and Jiguang Han equally contributed to this study.

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Jiang, Y., Han, J., Liu, J. et al. Risk of genome-wide association study newly identified genetic variants for breast cancer in Chinese women of Heilongjiang Province. Breast Cancer Res Treat 128, 251–257 (2011). https://doi.org/10.1007/s10549-010-1327-8

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  • DOI: https://doi.org/10.1007/s10549-010-1327-8

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