Two polymorphisms of the tumour necrosis factor gene do not influence survival in pancreatic cancer

Abstract

Polymorphisms of the tumour necrosis factor (TNF) gene have been related to TNF production and outcome in a variety of inflammatory and malignant diseases. Proinflammatory cytokines and the inflammatory state appear to affect outcome in pancreatic cancer. Thus, the present study examined the TNFB and TNF-308 polymorphisms for their relationship to the inflammatory state and survival in pancreatic cancer. Sixty-four patients with advanced pancreatic cancer and 101 healthy subjects were genotyped for each polymorphism. Serum concentrations of the two TNF receptors and C-reactive protein (CRP) were measured in 45 of the cancer patients with no evidence of infection or jaundice, 1 month after surgical intervention. There was no difference in distribution of genotypes between the patient and control groups. There was no association between any genotype and concentrations of any of the measured inflammatory mediators. While those with an elevated CRP concentration had significantly poorer survival, there was no association between either TNF genotype and survival. This study found no association between TNF genotype and the inflammatory state or survival in advanced pancreatic cancer. Other cytokines may be more important than TNF in determining the inflammatory state and disease progress in pancreatic cancer.

Fig. 1

TNFB Nco1 polymorphism. The polymerase chain reaction (PCR) was used to amplify a 368-bp fragment of the of the TNFβ genomic sequence and the PCR product was digested directly with 1 U of NcoI restriction enzyme. Lane 1 shows a homozygous for the cleaved product produced bands at 133 and 235 bp (with incomplete digestion of the 368-bp band) representing the allele TNFB1, while the uncleaved 368-bp product in lane 3 represents the allele TNFB2. Lane 2 shows a heterozygote pattern.

Fig. 2

TNF-308 G to A substitution. Polymerase chain reaction (PCR) was used to amplify a 107-bp fragment of the of the TNFβ genomic sequence which was digested with 1 U of NcoI. The cleaved product produced bands at 87 and 20 bp representing the TNF-308 A allele, while the uncleaved 107-bp product represented the TNF-308 G allele. Lanes 1–4, homozygote 87/20 TNF-308 A allele; lane 5, heterozygote 107, 87/20; lanes 6 and 7, homozygote 87/20; lane 8, homozygote 107 band TNF-308 G allele; lanes 9–11, homozygote 87/20 TNF-308 A allele.

Fig. 3

Serum concentrations of soluble tumour necrosis factor receptor (sTNF-R) I and II and C-reactive protein (CRP) from 45 patients with advanced pancreatic cancer with no evidence of infection or jaundice 4 weeks after surgery or bile duct stenting presented by TNFB and TNF-308 genotype. Statistical analysis by Kruskal–Wallis test.

Fig. 4

Kaplan–Meier survival curve of 45 patients with advanced pancreatic cancer with no evidence of infection or jaundice 4 weeks after surgery or bile duct stenting stratified for C-reactive protein (CRP). —-, CRP < 10 mg/l;–––––, CRP elevated. Comparison by log rank test, P = 0.0073.

Fig. 5

Kaplan–Meier survival curve of 64 patients with advanced pancreatic cancer for TNFB genotype. —-, 1/1; –––––, 1/2; ^·····, 2/2. Comparison by log rank test, P = 0.78.

Fig. 6

Kaplan–Meier survival curve of 64 patients with advanced pancreatic cancer for TNF-308 genotype. —-, G/G; –––––, G/A; ^·····, A/A. Comparison by log rank test, P = 0.13.