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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.

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).

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.

Background: Cervical cancer (CC) is still the second in prevalence and mortality among women. In spite of previously observed higher incidence of cervical dysplasia among systemic lupus erythematosus (SLE) patients, few studies have considered the influence of classic risk factors and the use of immunosuppressors (IM)., Objectives: To study cervical dysplasia prevalence among SLE patients submitted or not to immunosuppression and to evaluate its association with classic risk factors., Methods: A group of 171 SLE patients including 87 who were receiving IM continuously for at least 1 year was compared with 222 age- and sociocultural-paired women (control group) submitted to routine cervical cytopathology. Statistical methods included univariate and multivariate analysis, besides parametric and nonparametric tests., Results: The prevalence of atypical squamous cells of undetermined significance, low-grade and high-grade intraepithelial lesions were significantly increased in SLE patients (12.8%, 5.8%, and 3.5%, respectively) compared with controls (3.1%, 0.9%, and none, respectively, P = 0.0001), although they presented significantly fewer classic risk factors for CC. Multivariate analysis showed that SLE women had a 7-fold higher prevalence of cervical dysplasia (OR: 7.23, 95% IC: 3.40-15.38) and an 11-fold higher prevalence of premalignant cervical dysplasia (OR: 11.36, 95% IC: 2.57-50.10) compared with controls. SLE patients with long-term use of IM presented even higher prevalence of low-grade and high-grade intraepithelial lesions in comparison with those without long-term use of these agents (68.7% vs. 31.1%, P = 0.03)., Conclusions: This study provides evidence that even though not presenting the classic risk factors for CC, SLE patients, especially those exposed to long-term immunosuppression, have increased chances of presenting more premalignant lesions than the general population and they probably need to follow a more stringent CC prevention program.