Polymorphisms in the TGFB1 signal peptide influence human papillomavirus infection and development of cervical lesions

Abstract

The main purpose was to assess the effect of c.29C>T and c.74G>C polymorphisms in the TGFB1 signal peptide on HPV infection and development of cervical lesions. Cervical swabs and blood samples were obtained from 349 outpatient women, along with socio-demographic and sexual behavioral data. The study population was stratified by absence or presence of HPV DNA, as tested by PCR, as well as by lesion grade. TGFB1 signal peptide polymorphisms were genotyped using PCR-restriction fragment length polymorphism. HPV DNA was detected in 172 (49.3%) patients. c.74GC and the combined c.29CC+CT/c.74GC genotype were more frequent in infected patients (35.1 and 15.7%) than in uninfected women (6.2 and 14.7%). Accordingly, these genotypes were associated with a higher risk of HPV infection, with odds ratio and 95% confidence interval of 2.81 and 1.35-5.86 (P = 0.004) for c.74GC and 3.14 and 1.42-6.94 (P = 0.004) for the combined genotype, respectively. High-grade lesions were also 2.48 times more likely to occur in c.29CC patients than in c.29TT patients, with a 95% confidence interval of 1.01-6.08 (P = 0.047). The data demonstrate that c.74G>C and c.29C>T polymorphisms are significantly associated with risk of HPV infection and high-grade squamous intraepithelial lesions, respectively. Thus, TGFB1 signal peptide polymorphisms are potential susceptibility markers.

APOBEC3A/B Polymorphism Is Not Associated with Human Papillomavirus Infection and Cervical Carcinogenesis

“…We have shown here that smoking is related to cancer development and HPV infection, confirming previous studies by our group [ 27 , 29 , 34 ]. This association may be due to the fact that the DNA damage, immunosuppression, and epithelial dysplasia caused by cigarette components directly affect tumor development [ 35 ].…”

GSTT1 and GSTM1 Polymorphisms with Human Papillomavirus Infection in Women from Southern Brazil: A Case-control Study

“…The nal volume of each PCR (Polymerase Chain Reaction) reaction was 25 µl, containing, 10 mM Tris-HCl, 2 mM MgCl 2 , 0.1 mM dNTPs, 0.5 µM each primer, 1,25U of Taq DNA polymerase (Ludwig Biotechnology Taq DNA polymerase, Brazil), adding 3.5µl of total DNA at the end (50ng/µl). To control the extraction and synthesis process, PCR of a 268bp segment of the human β-globin gene was performed in all samples, using primers GH20 (5′-GAAGAGCCAAGGACAGGTAC-3′) and PCO4 (5′-CAACTTCATCCACGTTCACC-3′) [25]. The ampli cations of both genomes were processed in thermocycler Applied Biosystems Veriti Thermal Cycler (ThermoFisher Scienti c, Germany), following the steps: 10min at 94ºC, followed by 37 cycles of 1 min at 94ºC; 1min at 55ºC and 1 min at 72ºC; nishing with extension for 10 min at 72ºC [25].…”

“…To control the extraction and synthesis process, PCR of a 268bp segment of the human β-globin gene was performed in all samples, using primers GH20 (5′-GAAGAGCCAAGGACAGGTAC-3′) and PCO4 (5′-CAACTTCATCCACGTTCACC-3′) [25]. The ampli cations of both genomes were processed in thermocycler Applied Biosystems Veriti Thermal Cycler (ThermoFisher Scienti c, Germany), following the steps: 10min at 94ºC, followed by 37 cycles of 1 min at 94ºC; 1min at 55ºC and 1 min at 72ºC; nishing with extension for 10 min at 72ºC [25]. As a positive control for viral detection, a DNA sample from HeLLa cells (HPV 16) was included).…”

Personalized Human Papillomavirus Vaccination for Persistence of Immunity for Cervical Cancer Prevention: A Critical Review With Experts' Opinions

“…ii) Women with rapid-onset cervical disease can be examined to assess individual HPV exposures and the influence of molecular genetic factors (24,36). iii) Women with a high number of sexual partners (repeated exposure to oncogenic HPV infection), who do not develop cervical neoplasia can help to assess individual genetic factors for natural immunity to HPV persistent infection (37). iv) Older women with a persistent oncogenic HPV infection who do not develop cervical neoplasia can be examined to assess individual genetic factors for natural immunity to HPV persistent infection (37).…”