IFN-gamma and IL-12B polymorphisms in women with cervical intraepithellial neoplasia caused by human papillomavirus

Abstract

The Human Papillomavirus (HPV) is a sexually transmitted organism associated with Cervical Intraepithelial Neoplasia (CIN) and cervical cancer, the second main cause of malignancy in women worldwide. The virus itself, however, is not enough to cause lesions on the cervix. Several studies suggest that some polymorphic sites changes the cytokines levels and influence the cancer development in HPV infected patients. In this study, we evaluated the presence of functional polymorphisms at +874 (T/A) IFNG and +1188 (A/C) IL-12B genes in cervical smears samples from 76 healthy women and 162 women, HPV positive, with CIN lesion--CIN I (45), CIN II (55), CIN III (53) and cervical cancer (9)--in Brazilian population. There was no significant differences in genotype (p = 0.4192) and allele (p = 0.370; OR = 1.20) distributions between CIN patients and control groups on IFNG allelic polymorphism. Moreover, for IL-12B gene, there was a significant difference in genotype (p = 0.015) and allele distribution (p = 0.014; OR = 0.5754) between the groups. When samples were stratified according to grade of cervical lesion, the AA genotype and A allele were less frequent in the group with low-grade cervical lesions than in group with high-grade cervical lesions (p = 0.0036 and p = 0.0010; OR = 0.3819, respectively), suggesting that the C allele (mutant) may protect against the emergence of CIN lesions and its progression.

Interferon gamma +874 T/A polymorphism increases the risk of cervical cancer: evidence from a meta-analysis

“…We also excluded two articles on cervical intraepithelial neoplasia [9,16], and the significance of pooled ORs did not change. Five articles with scores of quality score assessment ≥10, which was considered Bhigh-quality^studies, were performed in a pooled analysis, and the results indicated no significant difference from the overall meta-analysis.…”

“…Based on the search terms, 20 articles were identified; one article was hand-searched, 13 articles were excluded according to the inclusion and exclusion criteria, and finally, eight articles including nine studies with 1,116 cases and 1,290 controls were identified as suitable for a meta-analysis [9][10][11][12][14][15][16][17] (Fig. 2).…”

“…2). Two studies focused on cervical intraepithelial neoplasia [9,16]. The study of Govan et al [12] involved different ethnicities, so it is treated as two separate studies in our meta-analysis.…”

“…Further sensitivity analysis was performed by excluding the studies by Linsingen et al [16] and Carvalho et al [9], in which the case population had developed cervical intraepithelial neoplasia. In particular, the specimens of cases determining genotypes were obtained from cervical smears in the study by Carvalho et al [9], and the significance of all ORs did not change.…”

“…According to the above mechanism, many studies have focused on the IFN-γ (+874 T/A) polymorphism and cancer risk, especially cancer caused by a virus, such as cervical cancer, which is caused by persistent high-risk HPV infection [9][10][11][12][13][14][15][16][17][18]. However, previous literature on the association between IFN-γ (+874 T/A) polymorphism and cervical cancer risk have provided contradictory results.…”