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/virologyABSTRACT
We investigated the importance of two adjacent functional polymorphisms in the Murine Double Minute 2 (MDM2) gene, SNP285 G > C and SNP309 T > G, for the development of cervical lesions in a Southeastern Brazilian population (293 cases and 184 controls). MDM2 genotyping was performed by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) and/or DNA sequencing. MDM2 SNP309 has potential as a biomarker of cervical neoplasia in non-smokers, patients with family history of cancer, or those who had late sexual debut (>16 years). Besides, this polymorphism may help identify women at risk of developing severe cervical lesion at a young age (<30 years).
Subject(s)
Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Proto-Oncogene Proteins c-mdm2/genetics , Uterine Cervical Neoplasms/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Brazil/epidemiology , Ethnicity , Female , Humans , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Risk Factors , Uterine Cervical Neoplasms/epidemiology , Young AdultABSTRACT
Variants of p16(INK4a) and p14(ARF), encoded by the CDKN2A locus, may respond differently to the presence of human papillomavirus (HPV). We investigated the potential association of two CDKN2A polymorphisms, 500C > G (rs11515) and 540C > T (rs3088440), with cervical neoplasia in patients with cervical lesions and healthy controls (n = 492). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single-strand conformation polymorphism (SSCP) and/or DNA sequencing techniques were employed for genotyping. The 500G allele was found higher, whereas the 540T/T genotype was less frequent in patients with more severe lesions. The CDKN2A variants may have the potential to be markers for the management of patients with cervical neoplasia.
