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.
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.
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.
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).
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.
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).
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.
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 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.
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.