Abstract
The purpose of the study was to investigate the potential associations between single-nucleotide polymorphisms (SNPs) in microRNA (miRNA)-binding sites in the integrin beta-1 (ITGB1) gene and integrin beta-3 (ITGB3) gene 3′-untranslated regions, and colorectal cancer (CRC) susceptibility in a Chinese population. A hospital-based case–control study was performed in 200 patients with CRC and 200 matched healthy donors. Two SNPs in miRNA binding of ITGB1 and ITGB3 genes (rs17468 and rs2317676) were genotyped by polymerase chain reaction-restrict fragment length polymorphism assay. The association between genotypes and CRC risk was evaluated by computing the odds ratio (OR) and 95 % confidence interval (CI) from multivariate unconditional logistic regression analyses. The frequency of the T genotype in ITGB1 rs17468 and G genotype in ITGB3 rs2317676 occurred more frequently in CRC patients than in controls (P < 0.05). We found that CT and TT genotypes of rs17468 were associated with a significantly increased risk of CRC (OR = 1.67, 95 % CI = 1.090–2.559 for CT + TT vs. CC), also the AG and GG genotype in ITGB3 rs2317676 (OR = 1.65, 95 % CI = 1.114–2.458 for AG + GG vs. AA). In conclusion, our results showed that both the ITGB1 rs17468 SNP and ITGB3 rs2317676 SNP were associated with an increased risk of CRC, which suggests that these 2 SNPs might contribute to CRC risk in a Chinese population.
Similar content being viewed by others
References
Peto, J. (2001). Cancer epidemiology in the last century and the next decade. Nature, 411(6835), 390–395. doi:10.1038/35077256.
Tsukuma, H., & Ajiki, W. (2003). Descriptive epidemiology of colorectal cancer-international comparison. Nippon Rinsho, 61(Suppl 7), 25–30.
Mou, X., Chen, L., Liu, F., Lin, J., Diao, P., Wang, H., et al. (2012). Prevalence of JC virus in Chinese patients with colorectal cancer. PLoS One, 7(5), e35900. doi:10.1371/journal.pone.0035900.
Zheng, X., Wang, L., Zhu, Y., Guan, Q., Li, H., Xiong, Z., et al. (2012). The SNP rs961253 in 20p12.3 is associated with colorectal cancer risk: A case–control study and a meta-analysis of the published literature. PLoS One, 7(4), e34625. doi:10.1371/journal.pone.0034625.
Takatsuno, Y., Mimori, K., Yamamoto, K., Sato, T., Niida, A., Inoue, H., et al. (2013). The rs6983267 SNP is associated with MYC transcription efficiency, which promotes progression and worsens prognosis of colorectal cancer. Annals of Surgical Oncology, 20(4), 1395–1402. doi:10.1245/s10434-012-2657-z.
Ivaska, J., & Heino, J. (2000). Adhesion receptors and cell invasion: Mechanisms of integrin-guided degradation of extracellular matrix. Cellular and Molecular Life Sciences, 57(1), 16–24. doi:10.1007/s000180050496.
Hynes, R. O. (1992). Integrins: Versatility, modulation, and signaling in cell adhesion. Cell, 69(1), 11–25. doi:10.1016/0092-8674(92)90115-S.
Ruoslahti, E., & Pierschbacher, M. D. (1987). New perspectives in cell adhesion: RGD and integrins. Science, 238(4836), 491–497. doi:10.1126/science.2821619.
Seales, E. C., Jurado, G. A., Brunson, B. A., Wakefield, J. K., Frost, A. R., & Bellis, S. L. (2005). Hypersialylation of beta1 integrins, observed in colon adenocarcinoma, may contribute to cancer progression by up-regulating cell motility. Cancer Research, 65(11), 4645–4652. doi:10.1158/0008-5472.CAN-04-3117.
Friedlander, M., Theesfeld, C. L., Sugita, M., Fruttiger, M., Thomas, M. A., Chang, S., et al. (1996). Involvement of integrins α v β3 and αv β 5 in ocular neovascular diseases. Proceedings of the National Academy of Sciences of the United States of America, 93(18), 9764–9769.
Brooks, P. C., Clark, R. A., & Cheresh, D. A. (1994). Requirement of vascular integrin α v β 3 for angiogenesis. Science, 264(5158), 569–571. doi:10.1126/science.7512751.
Gasparini, G., Brooks, P. C., Biganzoli, E., Vermeulen, P. B., Bonoldi, E., Dirix, L. Y., et al. (1998). Vascular integrin α (v) β3: A new prognostic indicator in breast cancer. Clinical Cancer Research, 4(11), 2625–2634.
Esquela-Kerscher, A., & Slack, F. J. (2006). Oncomirs—MicroRNAs with a role in cancer. Nature Reviews Cancer, 6(4), 259–269. doi:10.1038/nrc1840.
Yu, Z., Li, Z., Jolicoeur, N., Zhang, L., Fortin, Y., Wang, E., et al. (2007). Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers. Nucleic Acids Research, 35(13), 4535–4541. doi:10.1093/nar/gkm480.
Landi, D., Gemignani, F., Barale, R., & Landi, S. (2008). A catalog of polymorphisms falling in microRNA binding regions of cancer genes. DNA and Cell Biology, 27(1), 35–43. doi:10.1089/dna.2007.0650.
Iorio, M. V., Ferracin, M., Liu, C. G., Veronese, A., Spizzo, R., Sabbioni, S., et al. (2005). MicroRNA gene expression deregulation in human breast cancer. Cancer Research, 65(16), 7065–7070. doi:10.1158/0008-5472.CAN-05-1783.
Scott, G. K., Goga, A., Bhaumik, D., Berger, C. E., Sullivan, C. S., & Benz, C. C. (2006). Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. Journal of Biological Chemistry, 282(2), 1479–1486. doi:10.1074/jbc.M609383200.
Duan, R., Pak, C., & Jin, P. (2007). Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Human Molecular Genetics, 16(9), 1124–1131. doi:10.1093/hmg/ddm062.
Kim, S., Bell, K., Mousa, S. A., & Varner, J. A. (2000). Regulation of angiogenesis in vivo by ligation of integrin alpha5beta1 with the central cell-binding domain of fibronectin. American Journal of Pathology, 156(4), 1345–1362. doi:10.1016/S0002-9440(10)65005-5.
Klein, S., de Fougerolles, A. R., Blaikie, P., Khan, L., Pepe, A., Green, C. D., et al. (2002). α5β1 integrin activates an NF-kappa B-dependent program of gene expression important for angiogenesis and inflammation. Molecular and Cellular Biology, 22(16), 5912–5922. doi:10.1128/MCB.22.16.5912-5922.2002.
Silletti, S., Kessler, T., Goldberg, J., Boger, D. L., & Cheresh, D. A. (2001). Disruption of matrix metal proteinase binding to integrin alphav beta3 by an organic molecule inhibits angiogenesis and tumor growth in vivo. Proceedings of the National Academy of Sciences of the United States of America, 98(1), 119–124. doi:10.1073/pnas.98.1.119.
Chen, J. M., Ferec, C., & Cooper, D. N. (2006). A systematic analysis of disease-associated variants in the 3′ regulatory regions of human protein-coding genes I: General principles and overview. Human Genetics, 120(1), 1–21. doi:10.1007/s00439-006-0180-7.
Song, F., Zheng, H., Liu, B., Wei, S., Dai, H., Zhang, L., et al. (2009). An miR-502-binding site single-nucleotide polymorphism in the 3′-untranslated region of the SET8 gene is associated with early age of breast cancer onset. Clinical Cancer Research, 15(19), 6292–6300. doi:10.1158/1078-0432.CCR-09-0826.
Ratner, E., Lu, L., Boeke, M., Barnett, R., Nallur, S., Chin, L. J., et al. (2010). A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk. Cancer Research, 70(16), 6509–6515. doi:10.1158/0008-5472.CAN-10-0689.
Chin, L. J., Ratner, E., Leng, S., Zhai, R., Nallur, S., Babar, I., et al. (2008). A SNP in a let-7 micro RNA complementary site in the KARS 3′ untranslated region increases non-small cell lung cancer risk. Cancer Research, 68(20), 8535–8540. doi:10.1158/0008-5472.CAN-08-2129.
Dalmay, T., & Edwards, D. R. (2006). MicroRNAs and the hallmarks of cancer. Oncogene, 25(46), 6170–6175. doi:10.1038/sj.onc.1209911.
Zhang, J., Zhan, Z., Wu, J., Zhang, C., Yang, Y., Tong, S., et al. (2013). Association among polymorphisms in EGFR gene exons, lifestyle and risk of gastric cancer with gender differences in Chinese Han subjects. PLoS One, 8(3), e59254. doi:10.1371/journal.pone.0059254.
Magalhães, B., Peleteiro, B., & Lunet, N. (2012). Dietary patterns and colorectal cancer: Systematic review and meta-analysis. European Journal of Cancer Prevention, 21, 15–23.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ye, P., Li, Z., Jiang, H. et al. SNPs in MicroRNA-Binding Sites in the ITGB1 and ITGB3 3′-UTR Increase Colorectal Cancer Risk. Cell Biochem Biophys 70, 601–607 (2014). https://doi.org/10.1007/s12013-014-9962-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12013-014-9962-z