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Bone morphogenetic protein-4 polymorphism and colorectal cancer risk: a meta analysis

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Abstract

BMP4 rs4444235 is a candidate susceptibility allele that has been associated with an increased risk of colorectal cancer. This study was conducted to examine the association between BMP4 rs4444235 polymorphism and colorectal cancer risk. Odds ratio (ORs) with 95% CIs was pooled as effect indicator. A comprehensive search of related publications was conducted and those which met the inclusion criteria were included. Test of heterogeneity, meta-regression, subgroup analysis, cumulative meta-analysis, assessment of publication bias, and sensitivity test were performed using Stata 11.0. 8 articles on rs4444235 including 19,893 cases and 22,106 controls were included. There was slight heterogeneity which may come from ethnicity and source of control. Pooled results for all five genetic models were statistically significant. ORs were 1.063 (95% CI = (1.034, 1.092)), 1.081 (95% CI = (1.028, 1.136)), and 1.166(95% CI = (1.081, 1.258)) for C versus T, TC versus TT, and CC versus TT comparisons respectively. In Caucasian population, carriers of C allele, CC genotype and TC genotype were at an increased risk of developing CRC, with an OR of 1.079 (95% CI = (1.044, 1.114)), 1.095 (95% CI = (1.034, 1.159)), and 1.199 (95% CI = (1.117,1.287)) respectively. Cumulative meta-analysis indicated that pooled ORs were approximating 1.1 with publication year passing. No significant publication bias was suggested. Sensitivity test indicated stable results. In conclusion, BMP4-rs4444235 polymorphism is probably associated with CRC risk, and C allele is a possible risk factor in overall population. The same conclusion was drawn in Caucasians, but no significant results were obtained in other ethnic populations probably due to limited sample sizes.

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Abbreviations

BMP4:

Bone morphogenic protein 4

CRC:

Colorectal cancer

ORs:

Odds ratios

CIs:

Confidential intervals

References

  1. Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  2. Ferlay J, Bray F, Pisani P, Parkin DM (2004) GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. IARC Cancer Base No. 5. version 2.0. IARC Press, Lyon

    Google Scholar 

  3. Lichtenstein P, Holm NV, Verkasalo PK et al (2000) Environmental and heritable factors in the causation of cancer-analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85

    Article  PubMed  CAS  Google Scholar 

  4. Tenesa A, Dunlop MG (2009) New insights into the aetiology of colorectal cancer from genome-wide association studies. Nat Rev Genet 10(6):353–358

    Article  PubMed  CAS  Google Scholar 

  5. Wan DS (2009) Epidemiologic trend of and strategies for colorectal cancer. Chin J Cancer 28(9):897–902

    Google Scholar 

  6. Kim JS, Crooks H, Dracheva T et al (2002) Oncogenic ß -catenin is required for bone morphogenetic protein-4 expression in human cancer cells. Cancer Res 62(10):2744–2748

    PubMed  CAS  Google Scholar 

  7. Singh A, Morris RJ et al (2010) The Yin and Yang of bone morphogenetic proteins in cancer. Cytokine Growth Factor Rev 21:299–313

    Article  PubMed  CAS  Google Scholar 

  8. Lubbe SJ, Pittman AM, Matijssen C et al (2011) Evaluation of germline BMP4 mutation as a cause of colorectal cancer. Hum Mutat 32(1):1928–1938

    Article  Google Scholar 

  9. Deng H, Ravikumar TS, Yang WL (2009) Overexpression of bone morphogenetic protein 4 enhances the invasiveness of Smad4-deficient human colorectal cancer cells. Cancer Lett 281(2):220–231

    Article  PubMed  CAS  Google Scholar 

  10. Deng H, Makizumi R, Ravikumar TS, Dong H, Yang W et al (2007) Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells. Exp Cell Res 313:1033–1044

    Article  PubMed  CAS  Google Scholar 

  11. Deng H, Ravikumar TS, Yang WL (2007) Bone morphogenetic protein-4 inhibits heat-induced apoptosis by modulating MAPK pathways in human colon cancer HCT116 cells. Cancer Lett 256(2):207–217

    Article  PubMed  CAS  Google Scholar 

  12. Lombardo Y, Scopelliti A, Cammareri P et al (2011) Bone morphogenetic protein 4 induces differentiation of colorectal cancer stem cells and increases their response to chemotherapy in mice. Gastroenterology 140(1):297–309

    Article  PubMed  CAS  Google Scholar 

  13. Mancino M, Strizzi L, Wechselberger C et al (2008) Regulation of human Cripto-1 gene expression by TGF-beta1 and BMP-4 in embryonal and colon cancer cells. J Cell Physiol 215(1):192–203

    Article  PubMed  CAS  Google Scholar 

  14. Houlston RS, Webb E, Broderick P et al (2008) Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer. Nat Genet 40(12):1426–1435

    Article  PubMed  CAS  Google Scholar 

  15. Higgins JPT, Thompson SG, Deeks JJ et al (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560

    Article  PubMed  Google Scholar 

  16. Higgins JPT, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  17. Fernández-Rozadilla C, de Castro L, Clofent J et al (2010) Single nucleotide polymorphisms in the Wnt and BMP pathways and colorectal cancer risk in a Spanish cohort. PLoS ONE 5(9):e12673

    Article  PubMed  Google Scholar 

  18. Holst S, Picelli S, Edler D et al (2010) Association studies on 11 published colorectal cancer risk loci. Br J Cancer 103(4):575–580

    Article  Google Scholar 

  19. Xiong F, Wu C, Bi X et al (2010) Risk of genome-wide association study—identified genetic variants for colorectal cancer in a Chinese population. Cancer Epidemiol Biomarkers Prev 19(7):1855–1861

    Article  PubMed  CAS  Google Scholar 

  20. Ho JW, Choi S-C, Lee Y-F et al (2011) Replication study of SNP associations for colorectal cancer in Hong Kong Chinese. Br J Cancer 104:369–375

    Article  PubMed  CAS  Google Scholar 

  21. Mates IN, Csiki I, Mates D et al (2010) Association of common genetic variants with colorectal cancer risk in a Romanian sample. Chirurgia 105:749–757

    PubMed  CAS  Google Scholar 

  22. Kupfer SS, Anderson JR, Hooker S et al (2010) Genetic heterogeneity in colorectal cancer associations between African and European Americans. Gastroenterology 139:1677–1685

    Article  PubMed  CAS  Google Scholar 

  23. He J, Wilkens LR, Stram DO et al (2011) Generalizability and epidemiologic characterization of eleven colorectal cancer GWAS hits in multiple populations. Cancer Epidemiol Biomarkers Prev 20(1):70–81

    Article  PubMed  CAS  Google Scholar 

  24. Center MM, Jemal A, Smith RA, Ward E (2009) Worldwide variations in colorectal cancer. CA Cancer J Clin 59:366–378

    Article  PubMed  Google Scholar 

  25. Jakobsson M, Scholz SW, Scheet P et al (2008) Genotype, haplotype and copy-number variation in worldwide human populations. Nature 451:998–1003

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to express our gratitude to all the authors of included studies, especially Sonia Kupfer, Jing He and Ioan Nicolar Mates. This work was supported by Special funds for Basic Research and Operating Expenses in Central University (2011QN200) to Jing Wu.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, 430030, Wuhan, Hubei, China

    Jin Li, Chuang Sun, Yuerong Yuan, Li Liu, Guanglian Xiong & Jing Wu

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  1. Jin Li
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  2. Chuang Sun
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  3. Yuerong Yuan
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  4. Li Liu
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  5. Guanglian Xiong
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  6. Jing Wu
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Corresponding author

Correspondence to Jing Wu.

Additional information

Jin Li and Chuang Sun contributed equally to this article.

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Li, J., Sun, C., Yuan, Y. et al. Bone morphogenetic protein-4 polymorphism and colorectal cancer risk: a meta analysis. Mol Biol Rep 39, 5239–5251 (2012). https://doi.org/10.1007/s11033-011-1322-0

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  • DOI: https://doi.org/10.1007/s11033-011-1322-0

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