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Subject: Squamous intraepithelial lesions (SIL), cervical cancer (CCa), Human Papillomavirus (HPV), single nucleotide polymorphism (SNP), cancer and SIL susceptibility


Year: 2016


Type: Journal Article



Title: Association of p53Pro72Arg (rs1042522) and MDM2309 (rs2279744) polymorphisms with risk for cervical intraepthelial lesions and cervical cancer development in Macedonian women


Author: Sotirija Duvlis
Author: Marija Hiljadnikova-Bajro
Author: Dijana Plaseska Karanfilska



Abstract: High risk Human Papillomavirus (HPV) is an important etiological factor in initiation of squamous intraepithelial lesions (SIL), but not enough for malignant progression to cervical cancer (CCa). Single nucleotide polymorphisms (SNPs): rs1042522 within the codon 72 of p53 and rs2279744 within MDM2 promoter gene are plausible factors for development of SIL or CCa conferring increased attenuation of p53 pathway. We investigated the association of these SNPs with the HPV positive SIL and CCa among women from the Republic of Macedonia. Using a multiplex PCR SNaPShot analysis we genotyped rs1042522 and rs2279744 in 131 HPV positive women with SIL or CCa and 110 HPV and cytologicaly negative controls subject. No significant difference in either genotype or allelic frequencies for rs1042522 and rs2279744 between cases and control was found. The stratification of patients on the basis of the lesion grade revealed lower frequency of CC genotype and C allele of rs1042522 in HSIL and CCa compared to LSIL [GG vs CC; p=0.001, OR=0.4; CG vs CC; p=0.04, OR=0.03 and CG+ GG vs CC; p=0.004, OR=0.2]. Additionally TT genotype and T allele of MDM2 309 showed significantly lower frequency in HSIL and CCa group then in LSIL [G vs T p=0.02, OR=0.52; GG vs TT; p=0.04, OR=0.29; ТТ vs ТG+GG; p=0.007, OR=0.34].The Arg variant of rs1042522 and T allele/TT genotype of rs2279744 are associated with progression to LSIL to HSIL or CCa and may be used as prediction markers in CCa management, but the clinical relevant warrants further validation in large and well-designed studies.


Publisher:


Relation: Macedonian Pharmaceutial Bulletin



Identifier: oai:repository.ukim.mk:20.500.12188/25119
Identifier: Duvlis S., Hiljadnikova-Bajro M, Plaseska Karanfilska D. Association of p53Pro72Arg (rs1042522) and MDM2309 (rs2279744) polymorphisms with risk for cervical intraepthelial lesions and cervical cancer development in Macedonian women. Macedonian pharmaceutical bulletin. 2016. 62 (2) 49 - 58
Identifier: http://hdl.handle.net/20.500.12188/25119



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Association of p53Pro72Arg (rs1042522) and MDM2309 (rs2279744) polymorphisms with risk for cervical intraepthelial lesions and cervical cancer development in Macedonian women201623