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

Duvlis, Sotirija and Hiljadnikova-Bajro, Marija and Plaseska-Karanfilska, Dijana (2016) Association of p53Pro72Arg (rs1042522) and MDM2309 (rs2279744) polymorphisms with risk for cervical intraepithelial lesions and cervical cancer development in Macedonian women. Macedonian pharmaceutical bulletin. ISSN 1409 - 8695

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

Item Type:	Article
Subjects:	Medical and Health Sciences > Health sciences
Divisions:	Faculty of Medical Science
Depositing User:	Sotirija Duvlis
Date Deposited:	17 Feb 2023 09:47
Last Modified:	17 Feb 2023 09:47
URI:	https://eprints.ugd.edu.mk/id/eprint/31443

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