TY - JOUR
TI - Association of p16 (CDKN2A) polymorphisms with the development of HPV16-related precancerous lesions and cervical cancer in the Greek population
AU - Tsakogiannis, D.
AU - Moschonas, G.D.
AU - Bella, E.
AU - Kyriakopoulou, Z.
AU - Amoutzias, G.D.
AU - Dimitriou, T.G.
AU - Kottaridi, C.
AU - Markoulatos, P.
JO - Journal of Medical Virology
PY - 2018
VL - 90
TODO - 5
SP - 965-971
PB - John Wiley and Sons Inc
SN - 0146-6615, 1096-9071
TODO - 10.1002/jmv.24996
TODO - adult;  Article;  cancer growth;  cancer risk;  cancer susceptibility;  controlled study;  disease association;  disease severity;  DNA polymorphism;  female;  gene frequency;  genetic association;  genetic risk;  genetic susceptibility;  Greek (people);  haplotype;  human;  Human papillomavirus type 16;  human tissue;  major clinical study;  p16 gene;  polymerase chain reaction;  restriction fragment length polymorphism;  tumor suppressor gene;  uterine cervix carcinoma in situ;  uterine cervix dysplasia;  complication;  genetic predisposition;  genetics;  genotype;  Greece;  Human papillomavirus type 16;  isolation and purification;  middle aged;  papillomavirus infection;  prospective study;  squamous intraepithelial lesion of the cervix;  uterine cervix tumor;  virology, CDKN2A protein, human;  cyclin dependent kinase inhibitor 2A, Adult;  Cyclin-Dependent Kinase Inhibitor p16;  Female;  Genetic Predisposition to Disease;  Genotype;  Greece;  Human papillomavirus 16;  Humans;  Middle Aged;  Papillomavirus Infections;  Prospective Studies;  Squamous Intraepithelial Lesions of the Cervix;  Uterine Cervical Neoplasms
TODO - The tumor suppressor protein p16 plays a fundamental role in cell cycle regulation and exerts a protective effect against tumor growth. Two different polymorphisms at positions 540 and 580 at the 3′UTR of exon 3 of p16 gene are implicated in several types of cancer, while their role in cervical cancer development remains rather vague. In the present study, we investigated for the impact of p16 genotypes/haplotypes on patients' vulnerability to cervical disease and examined whether these factors can be used as progression markers in the Greek population. A total of 96 HPV16 positive samples and histologically confirmed as LSIL (42 samples), HSIL (44 samples), and cervical cancer cases (10 samples) along with 50 control cases were tested. The identification of p16 polymorphisms was performed by PCR-RFLP methodology. The present analysis revealed that women with p16 540 CG/GG genotype are at a 2.7-fold higher risk of developing HPV16-associated HSIL (OR = 2.7, 95%CI: 1.01-6.6, P = 0.028). The G allele can be regarded as a risk factor of developing HSIL in the Greek population (OR = 2.7, 95%CI: 1.2-5.9, P = 0.012). Moreover, p16 polymorphism C580T is not associated with the growth of cervical lesion in Greek patients, while 540G/580C haplotype can be regarded as a risk haplotype of developing HSIL (OR = 3.67, 95%CI: 1.56-8.6, P = 0.0019). Our results demonstrated that p16 C540G polymorphism influence patients' susceptibility to more severe dysplasia and consequently this polymorphism could potentially emerge as a valuable biomarker for HSIL development in the Greek population. © 2017 Wiley Periodicals, Inc.
ER -