Background: Cytokines genes polymorphisms have been suggested to favor cancer onset in response to triggering factors and drive tumor progression. Our aims were: (1) to evaluate IL-1b-31, IL-1RN (VNTR intron 2), CTGF-447, IFNg874, TNFa-1031, TNFa-863, TNFa-857, TNFa-308, IL-10-1082, IL-10-819, IL-10-592 genes polymorphisms in patients with pancreatic cancer (PC) or chronic pancreatitis (CP) in comparison with controls (CS); (2) to ascertain whether any of the above genes polymorphisms were associated with any clinical aspect of PC. Patients and Methods: 60 with PC (28 metastatic and 32 locally advanced; 16 had normal glucose tolerance, 7 glucose intollerance and 37 frank diabetes mellitus); 30 with CP and 78 CS. Genomic DNA was extracted from whole blood; all cytokines genes polymorphisms were PCR amplified and, excepted for IL-1RN, were RFLP analysed. Results: Only IL-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 IL-10-1082 A/A genotype was found (2 11.43, p 0.05). None of the studied polymorphisms was correlated with tumor stage or grade. Considering PC and CP all together (2 15.7, p 0.01), or PC alone (2 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 (2 14.48, p 0.01), but not to any cytokine studied polymorphism. Conclusions: IL-1b-31 and IL-10-1082 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 TNFalfa-863 polymorphisms favor the onset of chronic pancreatitis diseases and of associated diabetes, but not pancreatic cancer outcome
ZAMBON, CARLO-FEDERICO;FOGAR, PAOLA;BASSO, DANIELA;GRECO, ELIANA;PASQUALI, CLAUDIO;SPERTI, COSIMO;PEDRAZZOLI, SERGIO;PLEBANI, MARIO
2004
Abstract
Background: Cytokines genes polymorphisms have been suggested to favor cancer onset in response to triggering factors and drive tumor progression. Our aims were: (1) to evaluate IL-1b-31, IL-1RN (VNTR intron 2), CTGF-447, IFNg874, TNFa-1031, TNFa-863, TNFa-857, TNFa-308, IL-10-1082, IL-10-819, IL-10-592 genes polymorphisms in patients with pancreatic cancer (PC) or chronic pancreatitis (CP) in comparison with controls (CS); (2) to ascertain whether any of the above genes polymorphisms were associated with any clinical aspect of PC. Patients and Methods: 60 with PC (28 metastatic and 32 locally advanced; 16 had normal glucose tolerance, 7 glucose intollerance and 37 frank diabetes mellitus); 30 with CP and 78 CS. Genomic DNA was extracted from whole blood; all cytokines genes polymorphisms were PCR amplified and, excepted for IL-1RN, were RFLP analysed. Results: Only IL-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 IL-10-1082 A/A genotype was found (2 11.43, p 0.05). None of the studied polymorphisms was correlated with tumor stage or grade. Considering PC and CP all together (2 15.7, p 0.01), or PC alone (2 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 (2 14.48, p 0.01), but not to any cytokine studied polymorphism. Conclusions: IL-1b-31 and IL-10-1082 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.
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