Abstract
The aim of this study was to search for associations of genotypes and alleles of polymorphic loci of the PTEN/PI3K/AKT pathway genes rs2494750 of AKT1, rs2735343, rs2299941, rs10490920 of PTEN, rs17878362 of TP53, and rs2699887 of PIK3CA with the risk of prostate cancer development. As a result of comparison allele and genotype frequencies between the general sample of prostate cancer patients and the control group of healthy individuals, it was found that the CG genotype of the polymorphic locus rs2735343 of PTEN is associated with an increased risk of developing the disease (OR = 1.38, 95%CI = 1.02–1.87, p = 0.04), whereas the GG genotype showed a decrease in the frequency of occurrence in the group of patients compared with the control (OR = 0.74, 95%CI = 0.55–0.99, p = 0.05). When stratifying the group of patients with prostate cancer, depending on histopathological characteristics, it was revealed that the rs2735343*C allele is associated with an increased risk of bilateral lesions of both prostate lobes and invasion of seminal vesicles. With allowance for further validating studies, the results of this work can be used to create a panel of molecular markers for disease prognosis and assessment of tumor characteristics.
Similar content being viewed by others
REFERENCES
Bray, F., Ferlay, J., Soerjomataram, I., et al., Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, Ca-Cancer J. Clin., 2018, vol. 68, no. 6, pp. 394—424. https://doi.org/10.3322/CAAC.21492
Al Bashir, S., Alzoubi, A., Alfaqih, M.A., et al., PTEN loss in a prostate cancer cohort from Jordan, Appl. Immunohistochem. Mol. Morphol., 2020, vol. 28, no. 5, pp. 389—394. https://doi.org/10.1097/PAI.0000000000000732
Cucchiara, V., Cooperberg, M.R., Dall’Era, M., et al., Genomic markers in prostate cancer decision making, Eur. Urol., 2018, vol. 73, no. 4, pp. 572—582. https://doi.org/10.1016/J.EURURO.2017.10.036
Fitzgerald, L.M., Zhao, S., Leonardson, A., et al., Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: an analysis of 12 082 prostate cancer cases, Prostate Cancer Prostatic Dis., 2018, vol. 21, no. 2, p. 228. https://doi.org/10.1038/S41391-017-0029-2
Chun, S.H., Jung, C.K., Won, H.S., et al., Divergence of P53, PTEN, PI3K, Akt and mTOR expression in tonsillar cancer, Head Neck, 2015, vol. 37, no. 5, pp. 636—643. https://doi.org/10.1002/HED.23643
Shastry, B.S., SNPs: impact on gene function and phenotype, Methods Mol. Biol., 2009, vol. 578, pp. 3—22. https://doi.org/10.1007/978-1-60327-411-1_1
Pérez-Tenorio, G., Alkhori, L., Olsson, B., et al., PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer, Clin. Cancer Res., 2007, vol. 13, no. 12, pp. 3577—3584. https://doi.org/10.1158/1078-0432.CCR-06-1609
Lacey, J.V., Yang, H., Gaudet, M.M., et al., Endometrial cancer and genetic variation in PTEN, PIK3CA, AKT1, MLH1, and MSH2 within a population-based case-control study, Gynecol. Oncol., 2011, vol. 120, no. 2, pp. 167—173. https://doi.org/10.1016/J.YGYNO.2010.10.016
Slattery, M.L., Herrick, J.S., Lundgreen, A., et al., Genetic variation in a metabolic signaling pathway and colon and rectal cancer risk: mTOR, PTEN, STK11, RPKAA1, PRKAG2, TSC1, TSC2, PI3K and Akt1, Carcinogenesis, 2010, vol. 31, no. 9, pp. 1604—1611. https://doi.org/10.1093/CARCIN/BGQ142
Zhang, Z., Chen, Q., Zhang, J., et al., Associations of genetic polymorphisms in pTEN/AKT/mTOR signaling pathway genes with cancer risk: a meta-analysis in Asian population, Sci. Rep., 2017, vol. 7, no. 1, p. 17844. https://doi.org/10.1038/s41598-017-17250-z
Li, Q., Functional genetic variants in the mTORC1 related genes contribute to prostate cancer susceptibility and clinical outcomes (Doctoral thesis), Fudan Univ., Shanghai, China, 2014, p. 261.
Chen, J., Shao, P., Cao, Q., et al., Genetic variations in a PTEN/AKT/mTOR axis and prostate cancer risk in a Chinese population, PLoS One, 2012, vol. 7, no. 7. e40817. https://doi.org/10.1371/journal.pone.0040817
Cao, Q., Ju, X., Li, P., et al., A functional variant in the MTOR promoter modulates its expression and is associated with renal cell cancer risk, PLoS One, 2012, vol. 7, no. 11. e50302. https://doi.org/10.1371/journal.pone.0050302
Karyadi, D.M., Zhao, S., He, Q., et al., Confirmation of genetic variants associated with lethal prostate cancer in a cohort of men from hereditary prostate cancer families, Int. J. Cancer, 2015, vol. 136, no. 9, p. 2166. https://doi.org/10.1002/IJC.29241
Pu, X., Hildebrandt, M.A.T., Lu, C., et al., PI3K/PTEN/AKT/mTOR pathway genetic variation predicts toxicity and distant progression in lung cancer patients receiving platinum-based chemotherapy, Lung Cancer, 2011, vol. 71, no. 1, p. 82. https://doi.org/10.1016/J.LUNGCAN.2010.04.008
Mathew, C.G.P., The isolation of high molecular weight eukaryotic DNA, Nucleic Acids Res., 1984, vol. 2, pp. 31—34. https://doi.org/10.1385/0-89603-064-4:31
de Nóbrega, M., Cilião, H.L., de Souza, M.F., et al., Association of polymorphisms of PTEN, AKT1, PI3K, AR, and AMACR genes in patients with prostate cancer, Genet. Mol. Biol., 2020, vol. 43, no. 3, pp. 1—11. https://doi.org/10.1590/1678-4685-GMB-2018-0329
Chen, F.Y., Wang, H., Li, H., et al., Association of single-nucleotide polymorphisms in monoubiquitinated FANCD2-DNA damage repair pathway genes with breast cancer in the Chinese population, Technol. Cancer Res. Treat., 2018, vol. 17. https://doi.org/10.1177/1533033818819841
Ma, J., Zhang, J., Ning, T., et al., Association of genetic polymorphisms in MDM2, PTEN and P53 with risk of esophageal squamous cell carcinoma, J. Hum. Genet., 2012, vol. 57, no. 4, pp. 261—264. https://doi.org/10.1038/jhg.2012.15
Song, D.D., Zhang, Q., Li, J.H., et al., Single nucleotide polymorphisms rs701848 and rs2735343 in PTEN increases cancer risks in an Asian population, Oncotarget, 2017, vol. 8, no. 56, p. 96290. https://doi.org/10.18632/ONCOTARGET.22019
Petrov, S.B., Rakul, S.A., and Novikov, R.V., Extracapsular extension as a poor prognostic factor for prostate cancer, Vestn. Khir. im. I.I. Grekova, 2007, vol. 166, no. 3, pp. 93—98.
ACKNOWLEDGMENTS
This work was carried out on the equipment of the Center for Collective Use Biomics and the unique scientific installation KODINK, using DNA samples from the Center for Collective Use Collection of Human Biological Materials of the Institute of Biochemistry and Genetics of the Ural Federal Research Center of the Russian Academy of Sciences.
Funding
This study was performed with the partial financial support of the mega-grant of the Government of the Russian Federation no. 075-15-2021-595.
Author information
Authors and Affiliations
Contributions
I.R. Gilyazova and E.A. Ivanova contributed equally to this work.
Corresponding authors
Ethics declarations
Conflict of interest. The authors declare that they have no conflicts of interest.
Statement of compliance with standards of research involving humans as subjects. All procedures performed in a study involving people comply with the ethical standards of the institutional and/or national committee for research ethics and the 1964 Helsinki Declaration and its subsequent changes or comparable ethical standards. Informed voluntary consent was obtained from each of the participants.
Rights and permissions
About this article
Cite this article
Gilyazova, I.R., Ivanova, E.A., Bermisheva, M.A. et al. The Role of Polymorphic Variants of Gene Components of the PTEN/PI3K/AKT Signaling Pathway in the Development of Prostate Cancer. Russ J Genet 58, 844–849 (2022). https://doi.org/10.1134/S1022795422070055
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1022795422070055