Cytokines genes polymorphisms have been suggested to favor cancer onset in response to triggering factors and drive tumor progression. The aims of this study were to: 1. evaluate IL-lb-31, IL-1RN (VNTR intron 2), CTGF-447, IFNg + 874, TNFa-1031, TNFa-863, TNFa- 857, TNFa-308, 1L-10-1082, IL-10-819, IL-10-592 genes polymorphisms in patients with PC or chronic pancreatitis (CP) in comparison with controls (CS); 2. ascertain whether any of the above genes polymorphisms were associated with any clinical aspect of PC Patients: 60 with PC (28 metastatic and 32 locally advanced; 16 had normal glucose tolerance, 7 glucose intollerance and 37 frank diabetes melfitus); 30 with CP and 78 CS. Genomic DNA was extracted from whole blood; all cytokines genes polyraorphisms were PCR amplified and, excepted for 1L-1RN, were RFLP analysed. Only [L-10-819 and IL-10-592 were in complete linkage. A higher frequency of IL-1b-31 T/T genotype was found in CP (57%) as compared to CS (35%) or PC (42%). In PC (43%) and CP (41%) with respect to CS (31%) a higher frequency of 1L-10-1082 A/A genotype was found (Chi-square= 11.43, p<0.05). None of the studied polymorphisms was correlated with tumor stage or grade. Considering PC and CP all together (Chi-square = 15.7, p<0.01), or PC alone (Chi-square = 21.4, p<0.001), an association was found between TNFa-863 A allele and diabetes mellitus. Considering PC patients, TNFa-1031 T/T was associated with a slightly higher frequency of metastases (79%) after surgery, in comparison with C/T genotype (55%). Survival was correlated only to tumor stage (Chi-square = 14.48, p<0.O1), but not to any cytokine studied polymorphism Conclusions: lL-lb-31 and IL10-1082 gene polymorphisms might drive the onset of pancreatic cancer or chronic pancreatitis in response to triggering events, as already described for gastric or prostate cancer; TNFa-863 gene polymorphism seems that mainly involved in favoring diabetes development in patients with PC. Cytokines gene polymorphisms do not seem involved in affecting PC patients survival: only tumor stage was confirmed to predict the outcome of these patients.
Il10-1082 and TNFa-863 gene polymorphisms may favor the onset of chronic pancreatic diseases and of the associated diabetes, but not pancreatic cancer outcome
FOGAR, PAOLA;ZAMBON, CARLO-FEDERICO;BASSO, DANIELA;GRECO, ELIANA;PASQUALI, CLAUDIO;SPERTI, COSIMO;PEDRAZZOLI, SERGIO;PLEBANI, MARIO
2003
Abstract
Cytokines genes polymorphisms have been suggested to favor cancer onset in response to triggering factors and drive tumor progression. The aims of this study were to: 1. evaluate IL-lb-31, IL-1RN (VNTR intron 2), CTGF-447, IFNg + 874, TNFa-1031, TNFa-863, TNFa- 857, TNFa-308, 1L-10-1082, IL-10-819, IL-10-592 genes polymorphisms in patients with PC or chronic pancreatitis (CP) in comparison with controls (CS); 2. ascertain whether any of the above genes polymorphisms were associated with any clinical aspect of PC Patients: 60 with PC (28 metastatic and 32 locally advanced; 16 had normal glucose tolerance, 7 glucose intollerance and 37 frank diabetes melfitus); 30 with CP and 78 CS. Genomic DNA was extracted from whole blood; all cytokines genes polyraorphisms were PCR amplified and, excepted for 1L-1RN, were RFLP analysed. Only [L-10-819 and IL-10-592 were in complete linkage. A higher frequency of IL-1b-31 T/T genotype was found in CP (57%) as compared to CS (35%) or PC (42%). In PC (43%) and CP (41%) with respect to CS (31%) a higher frequency of 1L-10-1082 A/A genotype was found (Chi-square= 11.43, p<0.05). None of the studied polymorphisms was correlated with tumor stage or grade. Considering PC and CP all together (Chi-square = 15.7, p<0.01), or PC alone (Chi-square = 21.4, p<0.001), an association was found between TNFa-863 A allele and diabetes mellitus. Considering PC patients, TNFa-1031 T/T was associated with a slightly higher frequency of metastases (79%) after surgery, in comparison with C/T genotype (55%). Survival was correlated only to tumor stage (Chi-square = 14.48, p<0.O1), but not to any cytokine studied polymorphism Conclusions: lL-lb-31 and IL10-1082 gene polymorphisms might drive the onset of pancreatic cancer or chronic pancreatitis in response to triggering events, as already described for gastric or prostate cancer; TNFa-863 gene polymorphism seems that mainly involved in favoring diabetes development in patients with PC. Cytokines gene polymorphisms do not seem involved in affecting PC patients survival: only tumor stage was confirmed to predict the outcome of these patients.Pubblicazioni consigliate
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