Document Detail


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.
MedLine Citation:
PMID:  23280621     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Shehnaz K Hussain; Margaret M Madeleine; Lisa G Johnson; Qin Du; Denise A Galloway; Janet R Daling; Mari Malkki; Effie W Petersdorf; Stephen M Schwartz
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-02-12
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  133     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-04-22     Completed Date:  2013-06-11     Revised Date:  2013-11-21    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  201-13     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 UICC.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics*
Adult
Aged
Carcinoma, Squamous Cell / genetics*
Case-Control Studies
Female
Genetic Predisposition to Disease
Genotype
Humans
Interleukin-10 / genetics*
Interleukin-10 Receptor beta Subunit / genetics
Interleukin-12 / genetics*
Interleukin-12 Subunit p35 / genetics
Interleukin-12 Subunit p40 / genetics
Middle Aged
Nucleotides / genetics*
Odds Ratio
Parents
Polymorphism, Single Nucleotide*
Receptors, Interleukin-10 / genetics*
Receptors, Interleukin-12 / genetics*
Research Design
Risk Assessment
Risk Factors
Uterine Cervical Neoplasms / genetics*
Vulvar Neoplasms / genetics*
Grant Support
ID/Acronym/Agency:
K07 CA140360/CA/NCI NIH HHS; K07CA140360/CA/NCI NIH HHS; P01CA042792/CA/NCI NIH HHS; P30ES07033/ES/NIEHS NIH HHS; R01 CA112512/CA/NCI NIH HHS; R01CA112512/CA/NCI NIH HHS; R03CA108363/CA/NCI NIH HHS; R25CA087949/CA/NCI NIH HHS; R25CA094880/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/IL10 protein, human; 0/IL10RB protein, human; 0/IL12A protein, human; 0/IL12B protein, human; 0/IL12RB1 protein, human; 0/IL12RB2 protein, human; 0/Interleukin-10 Receptor beta Subunit; 0/Interleukin-12 Subunit p35; 0/Interleukin-12 Subunit p40; 0/Nucleotides; 0/Receptors, Interleukin-10; 0/Receptors, Interleukin-12; 130068-27-8/Interleukin-10; 187348-17-0/Interleukin-12

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