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Tumour Biol ; 37(8): 10469-78, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26846214

ABSTRACT

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.


Subject(s)
Adenocarcinoma/genetics , Carcinoma, Squamous Cell/genetics , Cyclin-Dependent Kinase Inhibitor p21/genetics , Neoplasm Proteins/genetics , Polymorphism, Single Nucleotide , Squamous Intraepithelial Lesions of the Cervix/genetics , Uterine Cervical Dysplasia/genetics , Uterine Cervical Neoplasms/genetics , Adenocarcinoma/epidemiology , Adenocarcinoma/pathology , Adenocarcinoma/virology , Adolescent , Adult , Aged , Aged, 80 and over , Brazil/epidemiology , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Case-Control Studies , Cyclin-Dependent Kinase Inhibitor p21/physiology , Ethnicity/genetics , Female , Gene Frequency , Genotype , Humans , Middle Aged , Neoplasm Proteins/physiology , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Prevalence , Squamous Intraepithelial Lesions of the Cervix/epidemiology , Squamous Intraepithelial Lesions of the Cervix/pathology , Squamous Intraepithelial Lesions of the Cervix/virology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Young Adult , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/virology
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