Τίτλος:
Gene expression polymorphisms of interleukins-1 beta, -4, -6, -8, -10,
and tumor necrosis factors-alpha, -beta: regression analysis of their
effect upon oral squamous cell carcinoma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose Functional DNA polymorphisms affecting gene expression and serum
or saliva levels of interleukins IL-1 beta,-4,-6,-8,-10 and tumor
necrosis factors TNF-alpha,-beta have been associated with increased
risk for the development of oral squamous cell carcinoma (OSCC). The
present retrospective case-control study examines possible interactions
between seven cytokine genotype polymorphisms and their combinatory
effect in predicting the occurrence of OSCC in Caucasians.
Methods Three hundred and thirty Greeks and Germans were studied,
consisting of 162 OSCC cases and 168 healthy controls of comparable age,
gender, and ethnicity. A series of multivariate logistic regression
models, adjusted for age and gender, was constructed in order to assess
the contribution of homozygous or heterozygous variant genotypes of
polymorphisms IL-1 beta (+3953C/T), IL-4 (-590C/T), IL-6 (-174G/C), IL-8
(-251A/T), IL-10 (-1082A/G), TNF-alpha (-308G/A) and TNF-beta (+252G/A)
upon overall, early and advanced stages of OSCC development.
Results The contribution of TNF-alpha and IL-6 was consistent and robust
in almost all models constructed. Furthermore, when the mode of
inheritance of each variant allele was taken into account in a
“biological” multivariate logistic regression model, four
polymorphisms emerged as primary predictors for overall stages of OSCC:
TNF-alpha (OR = 15.27; 95% CI = 7.30-31.96), IL-6 (OR = 8.33; 95% CI =
3.95-17.58), IL-8 (OR = 3.54; 95% CI = 1.69-7.43) and IL-10 (OR = 2.65;
95% CI = 1.28-5.46). Finally, IL-1 beta, IL-4 and TNF-beta
polymorphisms were not primary predictors of OSCC development in all
constructed models.
Conclusions This study revealed the highly significant contributions of
two out of seven studied cytokines (IL-6 and TNF-alpha) in the
occurrence of OSCC. Based on these findings and previous reports,
possible stoichiometrical interactions of cytokines leading to OSCC
development are discussed.
Συγγραφείς:
Vairaktaris, Eleftherios
Yapijakis, Christos
Serefoglou, Zoe and
Avgoustidis, Dimitrios
Critselis, Elena
Spyridonidou, Sofia and
Vylliotis, Antonis
Derka, Spyridoula
Vassiliou, Stavros and
Nkenke, Emeka
Patsouris, Efstratios
Περιοδικό:
Journal of Cancer Research and Clinical Oncology
Λέξεις-κλειδιά:
oral cancer; single nucleotide polymorphisms; cytokines; interleukins;
tumor necrosis factors
DOI:
10.1007/s00432-008-0360-z
