Tumor Biology

, Volume 36, Issue 4, pp 2703–2707 | Cite as

Genome-wide haplotype association study identifies BLM as a risk gene for prostate cancer in Chinese population

  • Qun Wang
  • Hongchao Lv
  • Wenhua Lv
  • Miao Shi
  • Mingming Zhang
  • Meiwei Luan
  • Hongjie Zhu
  • Ruijie Zhang
  • Yongshuai Jiang
Research Article


Prostate cancer (PC) is a common malignant tumor that occurs in the prostate epithelial cells. It is generally considered to be caused by both genetic and environmental factors. To identify the genetic risk factors of PC in Chinese population, we carried out a genome-wide haplotype-based association study. The 33 Chinese PC cases were from the public GEO database (GSE18333), and the 139 Chinese controls (CHB) were from the HapMap project. Our analysis included three stages: (1) identifying the linkage disequilibrium (LD) blocks and performing genome-wide haplotype association scan, (2) mapping PC-risk haplotypes to PC candidate genes, and (3) prioritizing PC candidate genes based on their similarity to known PC susceptibility genes. The results showed that (1) 749 haplotypes were significantly associated with PC (P < 1E−5). (2) Then, we mapped these significant haplotypes to genes and got 454 PC candidate genes. (3) After prioritizing the candidate genes based on their similarity to known PC susceptibility genes, we found that seven novel PC susceptibility genes including BLM, RPS6KA2, FRK, ERBB4, RBL1, PAK7, and ERBB2IP. Among the seven genes, BLM gene ranked first (P = 1.89E−04). A haplotype GGTTACCCCTC (rs2270131, rs2073919, rs11073953, rs12592875, rs16944863, rs2238337, rs414634, rs401549, rs17183344, rs16944884, and rs16944888) on chromosome 15q26.1 had significant association with PC (P = 2.37E−11). To our knowledge, this is the first genetic association study to show the significant association between BLM gene and PC susceptibility in Chinese population.


Genome-wide association study Prostate cancer Haplotype 



This work was supported in part by the National Natural Science Foundation of China (Grant Nos. 31200934) and the Natural Science Foundation of Heilongjiang Province, China (Grant Nos. C201206 and QC2013C063).

Conflicts of interest



  1. 1.
    Kovac JR, Pan MM, Lipshultz LI, Lamb DJ. Current state of practice regarding testosterone supplementation therapy in men with prostate cancer. Steroids. 2014;89:27–32.CrossRefPubMedGoogle Scholar
  2. 2.
    Gallagher RP, Fleshner N. Prostate cancer: 3. Individual risk factors. CMAJ. 1998;159:807–13.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Ganju A, Yallapu MM, Khan S, Behrman SW, Chauhan SC, Jaggi M. Nanoways to overcome docetaxel resistance in prostate cancer. Drug Resist Updat. 2014;17:13–23.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Dinkel A, Kornmayer M, Gschwend JE, Marten-Mittag B, Herschbach P, Herkommer K. Influence of family history on psychosocial distress and perceived need for treatment in prostate cancer survivors. Familial Cancer. 2014;13:481–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Lee MM, Gomez SL, Chang JS, Wey M, Wang RT, Hsing AW. Soy and isoflavone consumption in relation to prostate cancer risk in China. Cancer Epidemiol Biomark Prev : Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2003;12:665–8.Google Scholar
  6. 6.
    Mao X, Yu Y, Boyd LK, Ren G, Lin D, Chaplin T, et al. Distinct genomic alterations in prostate cancers in Chinese and Western populations suggest alternative pathways of prostate carcinogenesis. Cancer Res. 2010;70:5207–12.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    International HapMap C. The international hapmap project. Nature. 2003;426:789–96.CrossRefGoogle Scholar
  8. 8.
    Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, Gibbs RA, et al. A second generation human haplotype map of over 3.1 million snps. Nature. 2007;449:851–61.CrossRefPubMedGoogle Scholar
  9. 9.
    Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F, et al. Integrating common and rare genetic variation in diverse human populations. Nature. 2010;467:52–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Wang N, Akey JM, Zhang K, Chakraborty R, Jin L. Distribution of recombination crossovers and the origin of haplotype blocks: the interplay of population history, recombination, and mutation. Am J Hum Genet. 2002;71:1227–34.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Barrett JC: Haploview: visualization and analysis of SNP genotype data. Cold Spring Harb Protoc 2009;2009:pdb ip71.Google Scholar
  12. 12.
    Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Aerts S, Lambrechts D, Maity S, Van Loo P, Coessens B, De Smet F, et al. Gene prioritization through genomic data fusion. Nat Biotechnol. 2006;24:537–44.CrossRefPubMedGoogle Scholar
  14. 14.
    Tranchevent LC, Barriot R, Yu S, Van Vooren S, Van Loo P, Coessens B, et al. Endeavour update: a web resource for gene prioritization in multiple species. Nucleic Acids Res. 2008;36:W377–384.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Goodridge DM, Sloan JA, LeDoyen YM, McKenzie JA, Knight WE, Gayari M. Risk-assessment scores, prevention strategies, and the incidence of pressure ulcers among the elderly in four canadian health-care facilities. Can J Nurs Res = Revue Canadienne De Recherche En Sciences Infirmieres. 1998;30:23–44.PubMedGoogle Scholar
  16. 16.
    Sassi A, Popielarski M, Synowiec E, Morawiec Z, Wozniak K. Blm and rad51 genes polymorphism and susceptibility to breast cancer. Pathol Oncol Res. 2013;19:451–9.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Sokolenko AP, Iyevleva AG, Preobrazhenskaya EV, Mitiushkina NV, Abysheva SN, Suspitsin EN, et al. High prevalence and breast cancer predisposing role of the blm c.1642 c > t (q548x) mutation in russia. Int J Cancer. 2012;130:2867–73.CrossRefPubMedGoogle Scholar
  18. 18.
    Bignone PA, Lee KY, Liu Y, Emilion G, Finch J, Soosay AE, et al. Rps6ka2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer. Oncogene. 2007;26:683–700.CrossRefPubMedGoogle Scholar
  19. 19.
    Slattery ML, John EM, Torres-Mejia G, Lundgreen A, Herrick JS, Baumgartner KB, et al. Genetic variation in genes involved in hormones, inflammation and energetic factors and breast cancer risk in an admixed population. Carcinogenesis. 2012;33:1512–21.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Shi Q, Song X, Wang J, Gu J, Zhang W, Hu J, et al.: Frk inhibits migration and invasion of human glioma cells by promoting n-cadherin/beta-catenin complex formation. J Mol Neurosci 2014.Google Scholar
  21. 21.
    Kurppa KJ, Rokavec M, Sundvall M, Kellokumpu-Lehtinen PL, Joensuu H, Brauch H, et al. Erbb4 promoter polymorphism is associated with poor distant disease-free survival in high-risk early breast cancer. PLoS One. 2014;9:e102388.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Barh D, Jain N, Tiwari S, Field JK, Padin-Iruegas E, Ruibal A, et al. A novel in silico reverse-transcriptomics-based identification and blood-based validation of a panel of sub-type specific biomarkers in lung cancer. BMC Genomics. 2013;14 Suppl 6:S5.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Gu J, Li K, Li M, Wu X, Zhang L, Ding Q, et al. A role for p21-activated kinase 7 in the development of gastric cancer. FEBS J. 2013;280:46–55.CrossRefPubMedGoogle Scholar
  24. 24.
    Dai P, Xiong WC, Mei L. Erbin inhibits RAF activation by disrupting the Sur-8-Ras-Raf complex. J Biol Chem. 2006;281:927–33.CrossRefPubMedGoogle Scholar
  25. 25.
    Krstic M, Stajkovic N. [Risk for infection by lyme disease cause in green surfaces maintenance workers in Belgrade]. Vojnosanit Pregl Mil-Med Pharm Rev. 2007;64:313–8.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Qun Wang
    • 1
  • Hongchao Lv
    • 1
  • Wenhua Lv
    • 1
  • Miao Shi
    • 1
  • Mingming Zhang
    • 1
  • Meiwei Luan
    • 1
  • Hongjie Zhu
    • 1
  • Ruijie Zhang
    • 1
  • Yongshuai Jiang
    • 1
  1. 1.College of Bioinformatics Science and TechnologyHarbin Medical UniversityHarbinChina

Personalised recommendations