Polimorfismos de nucleotídeos único no gene IGFBP3 e o processo de carcinogênese: uma revisão sistemática





SNPs; Insulin-like growth Factor-binding protein 3; Cancer.


Introduction: Insulin-like growth factor binding protein -3 (IGFBP3) is the main mediator of IGF-1/IGF-1R binding, and may inhibit the binding between IGF-1 and IGF-1R and trigger cell growth suppression. Method: This study is a systematic review in which searches were conducted in Pubmed, Web of science, Science direct and Scopus databases for studies published in the period 2010-2020, including case-control studies that evaluated the association of polymorphisms in the IGFBP3 gene with cancer. Results: Of the 6 studies included, 5 were conducted in China and 1 in Iran, published in 2015 (n=2), 2014 (n=2), 2013 (n=1) and 2011 (n=1). In all, there were 5 types of cancer studied: esophagus (n=2), prostate (n=1), colorectal (n=1), breast (n=1) and gastric (n=1). In the studies chosen, 8 SNPs located in the IGFBP3 gene were evaluated: rs2854744, rs2854746, rs2132572, rs9282734, rs3110697, rs2960436, rs2270628 and rs10282088. Only the Zhao et al studies. (2015) and Liu et al. (2015) found a relationship between SNPs in the IGFBP3 gene with cancer. Two studies (Qian et al., 2014 and Qian et al., 2011) did not describe allelic frequencies in their results. Conclusion: Based on the studies we can demonstrate that the findings on the association of polymorphisms in the IGFBP3 gene with cancers are confusing, divergent and the role of the IGF pathway in carcinogenesis has not been clearly defined. However, the studies bring strong evidence that suggests possible relationships of this pathway and genetic variants with the carcinogenesis process in several types of cancer.


GLOBOCAN, International Agency for Research on Cancer. Estimated number of deaths in 2018, all cancers, females, all ages. Acesso em: 25/07/2020. Disponível em: <https://gco.iarc.fr/today/online-analysis table?v=2018&mode=cancer&mode_population=continents&population=900&populations=900&key=asr&sex=0&cancer=39&type=1&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&group_cancer=1&include_nmsc=1&include_nmsc_other=1>

ORGANIZAÇÃO PAN-AMERICANA DE SAÚDE. ORGANIZAÇÃO MUNDIAL DA SAÚDE. Folha informativa - Câncer. Acesso em: 25/07/2020. Disponível


Meijers, W. C., & de Boer, R. A. (2019). Common risk factors for heart failure and cancer. Cardiovascular research, 115(5), 844-853.

Tang, W., Chen, S., Liu, J., Liu, C., Wang, Y., & Kang, M. (2019). Investigation of IGF1, IGF2BP2, and IGFBP3 variants with lymph node status and esophagogastric junction adenocarcinoma risk. Journal of cellular biochemistry, 120(4), 5510-5518.

Wang, W., Wu, B. Q., Chen, G. B., Zhou, Y., Li, Z. H., Zhang, J. L., ... & Wang, J. Q. (2018). Meta-analysis of the association of IGFBP3 and IGF1 polymorphisms with susceptibility to colorectal cancer.

Chen, S., Qiu, H., Liu, C., Wang, Y., Tang, W., & Kang, M. (2018). Relationship between IGF2BP2 and IGFBP3 polymorphisms and susceptibility to non-small-cell lung cancer: a case–control study in Eastern Chinese Han population. Cancer Management and Research, 10, 2965.

Zhang, G., Zhu, Y., Liu, F., Gu, C., Chen, H., Xu, J., & Ye, D. (2016). Genetic variants in insulin-like growth factor binding protein-3 are associated with prostate cancer susceptibility in Eastern Chinese Han men. OncoTargets and therapy, 9, 61.

Bonilla, C., Lewis, S. J., Rowlands, M. A., Gaunt, T. R., Davey Smith, G., Gunnell, D., ... & Holly, J. M. (2016). Assessing the role of insulin‐like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels. International journal of cancer, 139(7), 1520-1533.

Qin, Z., Li, X., Tang, J., Jiang, X., Yu, Y., Wang, C., ... & Zhang, W. (2016). Association between insulin-like growth factor-binding protein-3 polymorphism-202 A/C and the risk of prostate cancer: a meta-analysis. OncoTargets and therapy, 9, 5451.

Terry, K. L., Tworoger, S. S., Gates, M. A., Cramer, D. W., & Hankinson, S. E. (2009). Common genetic variation in IGF1, IGFBP1 and IGFBP3 and ovarian cancer risk. Carcinogenesis, 30(12), 2042-2046.

Zhao, L., Chi, F., Xi, M., Shen, J. X., Li, Q. Q., He, L. R., ... & Liu, M. Z. (2015). Polymorphisms of insulin-like growth factor binding protein-3 as a predictor for risk and patient survival in esophageal squamous cell carcinoma. Biomedicine & Pharmacotherapy, 74, 148-152.

Qian, J., Zhou, H., Chen, J., Ding, Q., Cao, Q., Qin, C., ... & Yin, C. (2014). Genetic polymorphisms in IGF-I and IGFBP-3 are associated with prostate cancer in the Chinese population. PloS one, 9(2), e85609.

Karimi, K., Mahmoudi, T., Karimi, N., Dolatmoradi, H., Arkani, M., Farahani, H., ... & Zali, M. R. (2013). Is there an association between variants in candidate insulin pathway genes IGF-I, IGFBP-3, INSR, and IRS2 and risk of colorectal cancer in the Iranian population?. Asian Pacific Journal of Cancer Prevention, 14(9), 5011-5016.

Qian, B., Zheng, H., Yu, H., & Chen, K. (2011). Genotypes and phenotypes of IGF-I and IGFBP-3 in breast tumors among Chinese women. Breast cancer research and treatment, 130(1), 217.

Liu, C., Tang, W., Chen, S., Wang, Y., Qiu, H., Yin, J., & Gu, H. (2015). IGFBP3 polymorphisms and risk of esophageal cancer in a Chinese population. International journal of clinical and experimental medicine, 8(9), 17006.

Jun, G., Maolan, L., Ping, D., Jianhua, L., Zhujun, T., Xiangsong, W., ... & Yingbin, L. (2014). Role of polymorphisms of the IGF2 and IGFBP3 genes and risk of gastric carcinoma in China. Chinese Medical Journal, 127(3), 412-416.

Murphy, N., Carreras-Torres, R., Song, M., Chan, A. T., Martin, R. M., Papadimitriou, N., ... & Gunter, M. J. (2020). Circulating levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 associate with risk of colorectal cancer based on serologic and Mendelian randomization analyses. Gastroenterology, 158(5), 1300-1312.




How to Cite

FREITAS, P. P. de .; SANTOS, I. F. dos .; SILVA, D. M. da .; NASCIMENTO , C. A.; SANTOS, A. C. M. dos .; SILVA, A. C. P. e .; MOURA, E. L. de .; FIGUEIREDO, E. V. M. de S. .; FARIAS, K. F. de . Polimorfismos de nucleotídeos único no gene IGFBP3 e o processo de carcinogênese: uma revisão sistemática. Research, Society and Development, [S. l.], v. 10, n. 1, p. e48810111978, 2021. DOI: 10.33448/rsd-v10i1.11978. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/11978. Acesso em: 29 jan. 2023.



Review Article