Dataset Information

Nucleotide variation in IL-10 and IL-12 and their receptors and cervical and vulvar cancer risk: a hybrid case-parent triad and case-control study.

ABSTRACT: Given the important role of cell mediated immunity in viral clearance and control of premalignant lesions, we hypothesize that variation in the IL-12/IL-10 cytokine and cytokine receptor genes may influence cervical and vulvar cancer risk. We evaluated 76 tagSNPs from seven candidate genes (IL-10, IL-12A, IL-12B, IL-10RA, IL-10RB, IL-12RB1, and IL12RB2) in case-parent sets (n=43 cervical squamous cell carcinoma (SCC), n=96 cervical adenocarcinoma, n=53 vulvar SCC), additional cases (n=356 cervical SCC, n=406 cervical adenocarcinoma, and n=473 vulvar SCC) and population based controls (1,111). We calculated log-additive odds ratios (ORs) and 95% confidence intervals (CIs) for the association between tagSNP and cancer risk using a pseudo-likelihood based method which combined genotype information on cases, parents, and population controls. After correction for multiple comparisons, we identified several statistically significant SNP associations. Cervical SCC risk was associated with the minor alleles of the IL10RA rs9610 3' UTR SNP (OR=1.76, 95% CI=1.15-2.68) and two synonymous IL12RB2 SNPs (rs4297265, OR=0.46, 95% CI=0.26-0.82; rs2229546, OR=0.43, 95% CI=0.21-0.87). Cervical adenocarcinoma risk was associated with the minor alleles of the IL10RA rs4252314 intronic SNP (OR=2.23, 95% CI=1.26-3.96) and IL12RB1 rs11575934 non-synonymous SNP (OR=1.51, 95% CI=1.12-2.05). Finally, the minor allele of the IL12B rs3181224 3' UTR SNP was associated with a reduced risk of vulvar SCC (OR=0.30, 95% CI=0.12-0.74). These results raise the possibility that a shift in the balance of the immune response due to genetic variants in key cytokine genes could influence the development of cervical and vulvar cancer.

SUBMITTER: Hussain SK

PROVIDER: S-EPMC3833442 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nucleotide variation in IL-10 and IL-12 and their receptors and cervical and vulvar cancer risk: a hybrid case-parent triad and case-control study.

Hussain Shehnaz K SK Madeleine Margaret M MM Johnson Lisa G LG Du Qin Q Galloway Denise A DA Daling Janet R JR Malkki Mari M Petersdorf Effie W EW Schwartz Stephen M SM

International journal of cancer 20130212 1

Given the important role of cell mediated immunity in viral clearance and control of premalignant lesions, we hypothesize that variation in the IL-12/IL-10 cytokine and cytokine receptor genes may influence cervical and vulvar cancer risk. We evaluated 76 tagSNPs from seven candidate genes (IL-10, IL-12A, IL-12B, IL-10RA, IL-10RB, IL-12RB1, and IL12RB2) in case-parent sets (n=43 cervical squamous cell carcinoma (SCC), n=96 cervical adenocarcinoma, n=53 vulvar SCC), additional cases (n=356 cervic ...[more]

PMID: 23280621

Similar Datasets

Project description:BackgroundDiagnostic screenings for vulvar squamous intraepithelial lesions (VSIL) are limited and without information on disease trends. A panel of six methylation markers (ASTN1, DLX1, ITGA4, RXFP3, SOX17, ZNF671; GynTect® assay) has shown promise in diagnosing cervical intraepithelial neoplasia (CIN). Given the similarities between the carcinogenesis of cervix and vulva, this study aimed to investigate the suitability of these markers for diagnosing vulvar lesions.MethodsOne hundred twenty-one vulvar FFPE samples and 237 vulvar cell smears with different VSIL grades, HPV status, and with or without lichen sclerosus and planus were tested. Additionally, dysplasia-free vulvar cell smears from patients with cervical dysplasia were analyzed. The expression of DNA methyltransferases (DNMTs) in the FFPE samples was measured.ResultsThe markers demonstrated high specificity in vulvar smears, with sole 5.45% of dysplasia-free smears testing positive. Yet, 75.00% of vulvar carcinoma smears appear positive in the methylation kit, similar to VHSIL (VIN III) smears with 77.78%. In FFPE samples, dysplasia-free samples from the tumor microenvironment of high-grade vulvar neoplasia showed 43.75% positivity. The positivity rates for VSIL and carcinoma samples were 76.92%, 64.71%, 64.71%, and 80.49%, respectively. DNMT3a expression was the highest in VLSIL (VIN I) samples, while DNMT1 was only expressed in VHSIL (VIN III) and carcinoma samples. Lichen sclerosis and planus showed a high false positive rate of 45.45% for dysplasia-free and 54.54% for smears with dVIN. Cervical HSIL was associated with a significantly higher number of positive results in the kit than in patients without cervical dysplasia.ConclusionsThe findings suggest that the methylation markers comprising GynTect® may be suitable for detecting vulvar neoplasia, as they exhibit high sensitivity. Nonetheless, adjustments are needed for comparable specificity. Lichen should be considered in result interpretation, and the kit should be used with caution for patients with lichen. Moreover, we observed methylation changes as an early event with the highest positivity of VLSIL. Surprisingly, changes in methylation pattern are not as local as presumed. Cervical SIL led to changed methylation in the vulva. Patients with positive kit results should be monitored regularly for all genital dysplasia. This sheds new light on the epigenetics in cancer.

Dataset Information

Nucleotide variation in IL-10 and IL-12 and their receptors and cervical and vulvar cancer risk: a hybrid case-parent triad and case-control study.

Publications

Nucleotide variation in IL-10 and IL-12 and their receptors and cervical and vulvar cancer risk: a hybrid case-parent triad and case-control study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets