Roles of CDKN1A gene polymorphisms (rs1801270 and rs1059234) in the development of cervical neoplasia
- 139 Downloads
The CDKN1A gene product is a p53 downstream effector, which participates in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. The objective of our study was investigated the importance of two polymorphisms in the CDKN1A gene, rs1801270 (31C>A) and rs1059234 (70C>T), for the development of cervical lesions in a Southeastern Brazilian population (283 cases, stratified by lesion severity, and 189 controls). CDKN1A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or DNA sequencing. CDKN1A 31A allele presents a genetic pattern of protection for the development of high-grade cervical lesions (CC vs CA genotype: OR = 0.60; 95 % CI = 0.38–0.95; p = 0.029; CA+AA vs CC genotype: OR = 0.60; 95 % CI = 0.39–0.93; p = 0.021). Allele distributions of the CDKN1A 70C>T polymorphism were also different between the two study groups, with the CDKN1A 70T allele being less prevalent among cases. Moreover, the double heterozygote genotype combination 31CA-70CT decreases the chance of developing high-grade squamous intraepithelial lesion (HSIL) and cancer (OR = 0.55; 95 % CI = 0.32–0.93; p = 0.034) by 50 %, representing a protective factor against the development of more severe cervical lesions.
KeywordsCDKN1A Cervical neoplasia rs1801270 rs1059234 p21 Polymorphism
Compliance with ethical standards
Conflicts of interest
- 1.Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr. Accessed 05 July 2015.
- 5.Weinberg RA. How cancer arises. Sci Am. 1996;62–70.Google Scholar
- 9.Overton W, Spencerb SL, Noderera WL, Meyer T, Wang CL. Basal p21 controls population heterogeneity in cycling and quiescent cell cycle states. PNAS. 2014;e4386–93.Google Scholar
- 10.Souza H, Santos AM, Pinto D, Medeiros R. Is there a biological plausability for p53 codon 72 polymorphism influence on cervical cancer development? Acta Med Port. 2011;24:127–34.Google Scholar
- 12.Niehs Environmental Genome Project. [Internet] University of Washington. Available from: http://egp.gs.washington.edu/data/cdkn1a/. Accessed 25 Nov 14.
- 28.Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats your web tool for SNP analysis. [Internet] Bioinformatics. 2006;22:1928–9. Available from: http://bioinfo.iconcologia.net/snpstats/start.htm. Accessed 10 Aug 15.
- 32.Sun Y, Hildesheim A, Li H, Li Y, Chen JY, Cheng YJ, et al. No point mutation but a codon 31ser>arg polymorphism of the WAF-1/CIP-1/p21 tumor suppressor gene in nasopharyngeal carcinoma (NPC): the polymorphism distinguishes Caucasians from Chinese. Cancer Epidemiol Biomarkers Prev. 1995;4:261–7.PubMedGoogle Scholar
- 45.National Center for Biotechnology Information, U.S. National Library of Medicine. Available from: http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1059234. Accessed 08 Sept 2015
- 49.Solovyev V, Sagitov V. Softberry, Inc., 2015. Available from: http://www.softberry.com. Accessed on 08 Sept 2015.
- 50.Chang TH, Huang HY, Hsu JB, Weng SL, Horng JT, Huang HD. An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs. BMC Bioinf. 2013;14 Suppl2:S4. Available from: http://regrna2.mbc.nctu.edu.tw/. Accessed 08 Sept 2015.