Genetic determined downregulation of both type 1 and type 2 cytokine pathways might be protective against pancreatic cancer.
Many cytokine polymorphisms have been studied for associations with susceptibility to breast, gastric, liver, lung, prostate, and ovarian cancer without conclusive results. The cytokine network, indeed, is characterized by complex interactions, and the final biological effect of a single genetic variation depends on the balance among different molecular signals. As is well known, Th1/Th2 cytokine unbalanced production might predispose to different pathologies, cancer included. In general, a prolonged type 1 inflammatory response might allow that cells accumulating enough "genetic hits" are promoted to neoplastic transformation. On the other hand, IL-13-producing cells through the IL-13/IL-4 receptor-alpha (R-alpha) pathway might facilitate escape from tumor immunosurveillance. Here are reported data on the evaluation of the influence of some type 2 and type 1 cytokine genetic polymorphisms as risk factors for pancreatic cancer. There was no overall association between pancreatic cancer risk and single cytokine SNPs. On the other hand, in evaluating the influence of combined cytokine genotypes we found that the combined IL-10-1082GA heterozygous and IL-4 Ralpha-1902AA homozygous genotype is underrepresented in the pancreatic cancer subject group. As is well known, the IL-10-1082GA genotype is associated with an intermediate production of this regulatory cytokine, whereas the IL-10-1902AA genotype of the IL-4Ralpha gene is associated with a reduced efficiency in signal transduction when the receptor is engaged by IL-13 or IL-4. These results strongly suggest that a genetic background associated to a mild downregulation of type 1 and type 2 inflammatory signals might be protective against pancreatic cancer.
Scola
Letizia
L
Cattedra di Patologia Clinica, General Pathology Section, Department of Pathobiology and Biomedical Methodologies, University of Palermo, Corso Tuköry, Palermo, Italy.
Giacalone
Antonio
A
Marasà
Lorenzo
L
Mirabile
Monica
M
Vaccarino
Loredana
L
Forte
Giusi Irma
GI
Giannitrapani
Lydia
L
Caruso
Calogero
C
Montalto
Giuseppe
G
Lio
Domenico
D
D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000517:prevention & control*; D011110:Polymorphism, Genetic; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D016207:Cytokines