Taken together, these results suggest that TNF-308 AA and IL10-592 CA/AA genotypes may increase susceptibility to cervical cancer by altering the immune response of an individual.
Our studies found that IL-10 expression increased with pathological change levels and significantly correlated with cervical cancer differentiation (P < 0.05).
Therefore, this interplay between HPV and IL-10 creates a vicious cycle that could favor an immunosuppressive microenvironment in the cervix, facilitating the progression of a simple HPV infection to SIL or cervical cancer.
In summary, our findings demonstrate that elevated levels of PD-1/PD-L1, TGF-<i>β</i>, and IL-10 in peripheral blood of cervical cancer patients may negatively regulate immune response against cervical cancer cells and contribute to the progression of cervical cancer.
Individuals with at least one copy of the following risk alleles: T of SNP (-590C > T IL-4), C of SNP (-573G > C IL-6), A of SNP (-592C > A IL-10), T of SNP (-819C > T IL-10) and T of SNP (-509C > T TGFB1), had an adjusted odds ratio (OR) of 2.08 (95 % CI 1.475-2.934, p = 0.0001), an OR of 1.70 (95 % CI 1.208-2.404, p = 0.002), an OR of 1.87 (95 % CI 1.332-2.630, p = 0.0001), an OR of 1.67 (95 % CI 1.192-2.353, p = 0.003) and an OR of 1.91 (95 % CI 1.354-2.701, p = 0.0001), respectively, for CC.
The frequency of IL-10 -592 variant genotype (AA) was found significantly reduced in cases as compare to controls while -1082 variant genotype (GG) was found ~4-fold higher risk of cervical cancer (p = <0.0001, OR = 3.667, 95% CI = 2.329-5.773).
In the subgroup analysis by ethnicity, IL-10 -1082A allele was associated with decreased cervical cancer susceptibility among whites (A vs G: OR, 0.39; 95% confidence interval [CI], 0.32-0.47).
However, individuals carrying heterozygous genotype for TNF-α -238 polymorphism seem to be at lower risk for cervical cancer development, with borderline significance (OR = 0.42, P = 0.069), as well as those carrying heterozygous genotypes for IL-10 and TNF-α -238 (OR = 0.40, P = 0.08).
This study suggests that passive smokers among North Indian women having IL-4 Rp1/Rp2 and IL-10 (AC) genotypes had an increased risk for developing cervical cancer.
In particular, IL-10 is highly expressed in tumor cells and its expression is directly proportional to the development of HPV-positive cervical cancer, suggesting an important role of HPV proteins in the expression of IL-10.
In conclusion, our data suggest that interleukin-10 -1082 gene polymorphism may serve as a marker of genetic susceptibility to cervical cancer among Japanese women.
These results suggest a clear relationship between IL-10, HPV and the stage of cervical cancer disease; this event could contribute to the immunosuppressive micro-environment in the tumor site.
We did not find any association for IL-10 -592, or FasL -844, previously reported to be associated with cervical cancer in the Dutch and Chinese populations, respectively.
These results support the hypothesis that IL10 polymorphisms influence the clearance of infection with high-risk HPV types and warrant further studies of host genetic control of HPV pathogenesis and cervical cancer in the context of immunosuppression.
We examined in a large study population whether three polymorphisms in the IL-10 gene and a polymorphism at position -670 of the Fas promotor affect susceptibility for cervical cancer or its precursor.
These data suggest that the genetically acquired ability to produce higher levels of IL-10 may be a significant factor in the development of cervical cancer.