A Burguete-García

A García-Carrancá

D Cantú

E Ortíz-Flores

K Delgado-Romero

K Torres-Poveda

M Bahena-Román

V Madrid-Marina

BMC Proceedings

PubMed

Torres-Poveda, K.

Burguete-García, A.

Bahena-Román, M.

Ortíz-Flores, E.

Delgado-Romero, K.

Cantú, D.

García-Carrancá, A.

Madrid-Marina, V.

Sexual Reproductive Health and Rights Repository (Aga Khan University)

POSTER PRESENTATION Open AccessA functional role of the SNP -592 of human IL10gene regulatory region is associated with anincreased IL-10 expression and risk for humanpapillomavirus cervical lesion and cervical cancerdevelopmentK Torres-Poveda1, A Burguete-García1, M Bahena-Román1, E Ortíz-Flores1, K Delgado-Romero2, D Cantú3,A García-Carrancá3, V Madrid-Marina1*From Beyond the Genome 2012Boston, MA, USA. 27-29 September 2012BackgroundAn immunosuppressive state had been identified inwomen with persistent infection by the human papilloma-virus (HPV), characterized by high levels of interleukin(IL)10 at cervix level [1]. The present study analyzed theassociation of SNPs in the regulatory region of the IL10gene with the risk of developing squamous intraepitheliallesions of the cervix (SIL) and cervical cancer (CC), andevaluated the level of mRNA expression of IL10 (mRNA-IL10) systemically and in the cervix and the IL10 proteinlevel in serum.Materials and methodsUsing a cross-sectional design, samples of peripheral bloodof patients with SIL (n = 204), patients with CC (n = 80)and patients without SIL (n = 166) were used to evaluateSNPs at loci -592A/C (rs1800872), -819C/T (rs1800871),-1082A/G (rs1800896) and -1352A/G (rs1800893) by alle-lic discrimination with Taqman probes and evaluating themRNA-IL10. Cervical swabs in women without SIL andcervical biopsies in women with SIL and CC were used forHPV typing and evaluation of mRNA-IL10. Gene expres-sion levels were evaluated by real-time PCR. The genotypeand allele frequencies of polymorphisms were analyzedusing logistic regression, adjusting for age and genotype ofHPV, to determine the association with SIL and CC.ResultsNo significant differences were found between the fre-quencies of genotypes at loci -819, -1082 and -1352. Indi-viduals who carried at least one copy of the risk allele A ofSNP -592, showed an odds ratio (OR) of 2.02 (95% CI 1.26to 3.25, P<0.003) for SIL, an OR of 1.70 (95% CI 1.06 to2.71, P<0.02) for CC, and higher levels of IL10 systemicallyand in the cervix. Thus, a copy of the risk allele A is suffi-cient to increase the risk of SIL and CC. We found a sig-nificant difference in mRNA-IL10 in both systemic andthe cervical levels in women with SIL and CC comparedwith women without SIL, and in the serum IL10 protein(P < 0.0001), being higher in patients carrying the riskallele A of SNP -592. The levels of both mRNA-IL10 andIL10 protein were progressively higher with increasingdegree of malignancy of the lesion, so that the presence ofIL10 can be regarded as a relevant factor for viral persis-tence and progression of disease.ConclusionsThe SNP -592 C/A in the IL10 promoter is associatedwith increased risk of SIL and CC and can serve as a bio-marker predictive of risk for the development of SIL inthe cervix and CC in Mexican women, and is associatedwith the regulation of this cytokine expression in bothcervical and systemic level. HPV 16 E6/E7 proteins bind1Chronic Infection Diseases and Cancer Division, Centro de Investigaciónsobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública,Cuernavaca, Morelos, MexicoFull list of author information is available at the end of the articleTorres-Poveda et al. BMC Proceedings 2012, 6(Suppl 6):P27http://www.biomedcentral.com/1753-6561/6/S6/P27© 2012 Torres-Poveda et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.to Sp1 transcription factor and upregulate IL10 geneexpression though a GGGGCGG consensus sequencelocated at -596 to -603 of the human IL10 gene, and theC/A exchange in the SNP -592 results in increased IL10gene promoter activity in HPV-transformed cells.Author details1Chronic Infection Diseases and Cancer Division, Centro de Investigaciónsobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública,Cuernavaca, Morelos, Mexico. 2Center for health of woman (CAPASAM),Health Services of State of Morelos, Cuernavaca, Mexico. 3Unit of BiomedicalResearch in Cancer, Instituto Nacional de Cancerología/Biomedical ResearchInstitute, National Autonomous University of Mexico, Mexico City, Mexico.Published: 1 October 2012Reference1. Guzmán-Olea E, Bermúdez-Morales VH, Peralta-Zaragoza O, Torres-Poveda K,Madrid-Marina V: Molecular mechanisms and potential targets toblocking HPV-induced lesion development. J Oncol 2012, 2012:278312.doi:10.1186/1753-6561-6-S6-P27Cite this article as: Torres-Poveda et al.: A functional role of the SNP-592 of human IL10 gene regulatory region is associated with anincreased IL-10 expression and risk for human papillomavirus cervicallesion and cervical cancer development. BMC Proceedings 20126(Suppl 6):P27.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitTorres-Poveda et al. BMC Proceedings 2012, 6(Suppl 6):P27http://www.biomedcentral.com/1753-6561/6/S6/P27Page 2 of 2

A functional role of the SNP -592 of human IL10 gene regulatory region is associated with an increased IL-10 expression and risk for human papillomavirus cervical lesion and cervical cancer development

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Springer - Publisher Connector

POSTER PRESENTATION Open Access
A functional role of the SNP -592 of human IL10
gene regulatory region is associated with an
increased IL-10 expression and risk for human
papillomavirus cervical lesion and cervical cancer
development
K Torres-Poveda1, A Burguete-García1, M Bahena-Román1, E Ortíz-Flores1, K Delgado-Romero2, D Cantú3,
A García-Carrancá3, V Madrid-Marina1*
From Beyond the Genome 2012
Boston, MA, USA. 27-29 September 2012
Background
An immunosuppressive state had been identified in
women with persistent infection by the human papilloma-
virus (HPV), characterized by high levels of interleukin
(IL)10 at cervix level [1]. The present study analyzed the
association of SNPs in the regulatory region of the IL10
gene with the risk of developing squamous intraepithelial
lesions of the cervix (SIL) and cervical cancer (CC), and
evaluated the level of mRNA expression of IL10 (mRNA-
IL10) systemically and in the cervix and the IL10 protein
level in serum.
Materials and methods
Using a cross-sectional design, samples of peripheral blood
of patients with SIL (n = 204), patients with CC (n = 80)
and patients without SIL (n = 166) were used to evaluate
SNPs at loci -592A/C (rs1800872), -819C/T (rs1800871),
-1082A/G (rs1800896) and -1352A/G (rs1800893) by alle-
lic discrimination with Taqman probes and evaluating the
mRNA-IL10. Cervical swabs in women without SIL and
cervical biopsies in women with SIL and CC were used for
HPV typing and evaluation of mRNA-IL10. Gene expres-
sion levels were evaluated by real-time PCR. The genotype
and allele frequencies of polymorphisms were analyzed
using logistic regression, adjusting for age and genotype of
HPV, to determine the association with SIL and CC.
Results
No significant differences were found between the fre-
quencies of genotypes at loci -819, -1082 and -1352. Indi-
viduals who carried at least one copy of the risk allele A of
SNP -592, showed an odds ratio (OR) of 2.02 (95% CI 1.26
to 3.25, P<0.003) for SIL, an OR of 1.70 (95% CI 1.06 to
2.71, P<0.02) for CC, and higher levels of IL10 systemically
and in the cervix. Thus, a copy of the risk allele A is suffi-
cient to increase the risk of SIL and CC. We found a sig-
nificant difference in mRNA-IL10 in both systemic and
the cervical levels in women with SIL and CC compared
with women without SIL, and in the serum IL10 protein
(P < 0.0001), being higher in patients carrying the risk
allele A of SNP -592. The levels of both mRNA-IL10 and
IL10 protein were progressively higher with increasing
degree of malignancy of the lesion, so that the presence of
IL10 can be regarded as a relevant factor for viral persis-
tence and progression of disease.
Conclusions
The SNP -592 C/A in the IL10 promoter is associated
with increased risk of SIL and CC and can serve as a bio-
marker predictive of risk for the development of SIL in
the cervix and CC in Mexican women, and is associated
with the regulation of this cytokine expression in both
cervical and systemic level. HPV 16 E6/E7 proteins bind
1Chronic Infection Diseases and Cancer Division, Centro de Investigación
sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública,
Cuernavaca, Morelos, Mexico
Full list of author information is available at the end of the article
Torres-Poveda et al. BMC Proceedings 2012, 6(Suppl 6):P27
http://www.biomedcentral.com/1753-6561/6/S6/P27
© 2012 Torres-Poveda et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
to Sp1 transcription factor and upregulate IL10 gene
expression though a GGGGCGG consensus sequence
located at -596 to -603 of the human IL10 gene, and the
C/A exchange in the SNP -592 results in increased IL10
gene promoter activity in HPV-transformed cells.
Author details
1Chronic Infection Diseases and Cancer Division, Centro de Investigación
sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública,
Cuernavaca, Morelos, Mexico. 2Center for health of woman (CAPASAM),
Health Services of State of Morelos, Cuernavaca, Mexico. 3Unit of Biomedical
Research in Cancer, Instituto Nacional de Cancerología/Biomedical Research
Institute, National Autonomous University of Mexico, Mexico City, Mexico.
Published: 1 October 2012
Reference
1. Guzmán-Olea E, Bermúdez-Morales VH, Peralta-Zaragoza O, Torres-Poveda K,
Madrid-Marina V: Molecular mechanisms and potential targets to
blocking HPV-induced lesion development. J Oncol 2012, 2012:278312.
doi:10.1186/1753-6561-6-S6-P27
Cite this article as: Torres-Poveda et al.: A functional role of the SNP
-592 of human IL10 gene regulatory region is associated with an
increased IL-10 expression and risk for human papillomavirus cervical
lesion and cervical cancer development. BMC Proceedings 2012
6(Suppl 6):P27.
Submit your next manuscript to BioMed Central
and take full advantage of: 
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at 
www.biomedcentral.com/submit
Torres-Poveda et al. BMC Proceedings 2012, 6(Suppl 6):P27
http://www.biomedcentral.com/1753-6561/6/S6/P27
Page 2 of 2


Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color ﬁgure charges • Immediate publication on acceptance

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A functional role of the SNP -592 of human IL10 gene regulatory region is associated with an increased IL-10 expression and risk for human papillomavirus cervical lesion and cervical cancer development

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