Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study
Por:
Torres-Poveda, K., Burguete-Garcia, A. I., Bahena-Roman, M., Mendez-Martinez, R., Zurita-Diaz, M. A., Lopez-Estrada, G., Delgado-Romero, K., Peralta-Zaragoza, O., Bermudez-Morales, V. H., Cantu, D., Garcia-Carranca, A., Madrid-Marina, V.
Publicada:
24 may 2016
Resumen:
Background: Alterations in the host cellular immune response allow
persistent infections with High-Risk Human Papillomavirus (HR-HPV) and
development of premalignant cervical lesions and cervical cancer (CC).
Variations of immunosuppressive cytokine levels in cervix are associated
with the natural history of CC. To assess the potential role of genetic
host immunity and cytokines serum levels in the risk of developing CC,
we conducted a case-control study paired by age.
Methods: Peripheral blood samples from patients with CC (n = 200) and
hospital controls (n = 200), were used to evaluate nine biallelic SNPs
of six cytokine genes of the adaptive immune system by allelic
discrimination and cytokines serum levels by ELISA.
Results: After analyzing the SNP association by multivariate logistic
regression adjusted by age, CC history and smoking history, three Th2
cytokines (IL-4, IL-6 and IL-10) and one Th3 (TGFB1) cytokine were
significantly associated with CC. 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 burden of carrying
two or more of these risk alleles was found to have an additive effect
on the risk of CC (p trend = 0.0001). Finally, the serum levels of Th2
and Th3 cytokines were higher in CC cases than the controls; whereas
IFNG levels, a Th1 cytokine, were higher in controls than CC cases.
Conclusion: The significant associations of five SNPs with CC indicate
that these polymorphisms are potential candidates for predicting the
risk of development of CC, representing a risk allelic load for CC and
can be used as a biomarker of susceptibility to this disease.
Filiaciones:
Torres-Poveda, K.:
Natl Inst Publ Hlth Mexico, Direcc Infecc Cron & Canc, Ctr Invest Enfermedades Infecciosas, INSP,Chron Infect Dis & Canc Div,Ctr Res Infect D, Av Univ 655, Cuernavaca 62100, Morelos, Mexico
INSP, CONACyT, Cuernavaca, Morelos, Mexico
Burguete-Garcia, A. I.:
Natl Inst Publ Hlth Mexico, Direcc Infecc Cron & Canc, Ctr Invest Enfermedades Infecciosas, INSP,Chron Infect Dis & Canc Div,Ctr Res Infect D, Av Univ 655, Cuernavaca 62100, Morelos, Mexico
Bahena-Roman, M.:
Natl Inst Publ Hlth Mexico, Direcc Infecc Cron & Canc, Ctr Invest Enfermedades Infecciosas, INSP,Chron Infect Dis & Canc Div,Ctr Res Infect D, Av Univ 655, Cuernavaca 62100, Morelos, Mexico
Mendez-Martinez, R.:
Inst Nacl Cancerol INCan, Div Basic Res, Ss Mexico City, Mexico
Zurita-Diaz, M. A.:
Natl Inst Publ Hlth Mexico, Direcc Infecc Cron & Canc, Ctr Invest Enfermedades Infecciosas, INSP,Chron Infect Dis & Canc Div,Ctr Res Infect D, Av Univ 655, Cuernavaca 62100, Morelos, Mexico
Lopez-Estrada, G.:
Private Hlth Ctr Gynecol, Cuernavaca, Morelos, Mexico
Delgado-Romero, K.:
Ctr Womens Hlth, Ctr Atenc Salud Mujer CAPASAM, Hlth Serv State Morelos, Cuernavaca, Morelos, Mexico
Peralta-Zaragoza, O.:
Natl Inst Publ Hlth Mexico, Direcc Infecc Cron & Canc, Ctr Invest Enfermedades Infecciosas, INSP,Chron Infect Dis & Canc Div,Ctr Res Infect D, Av Univ 655, Cuernavaca 62100, Morelos, Mexico
Bermudez-Morales, V. H.:
Natl Inst Publ Hlth Mexico, Direcc Infecc Cron & Canc, Ctr Invest Enfermedades Infecciosas, INSP,Chron Infect Dis & Canc Div,Ctr Res Infect D, Av Univ 655, Cuernavaca 62100, Morelos, Mexico
Cantu, D.:
Inst Nacl Cancerol INCan, Div Clin Res, Ss Mexico City, Mexico
Garcia-Carranca, A.:
Inst Nacl Cancerol INCan, Div Basic Res, Ss Mexico City, Mexico
Univ Nacl Autonoma Mexico, SS & Biomed Res Inst, Inst Nacl Cancerol INCan, Unit Biomed Res Canc, Mexico City 04510, DF, Mexico
Madrid-Marina, V.:
Natl Inst Publ Hlth Mexico, Direcc Infecc Cron & Canc, Ctr Invest Enfermedades Infecciosas, INSP,Chron Infect Dis & Canc Div,Ctr Res Infect D, Av Univ 655, Cuernavaca 62100, Morelos, Mexico
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