title: TNFα gene/protein in tumorigenesis of sporadic colon adenocarcinoma.
abstract: OBJECTIVE
  Inherited polymorphisms in immunomodulatory genes such as cytokines may contribute to variation in immunological response and genetic susceptibility for complex diseases, including cancer. TNFα can mediate tumor progression by inducing proliferation, invasion and metastasis of tumor cells. The aim of our study was to examine the allelic frequencies of TNFα promoter SNPs, -1031 T/C, -857 C/T, -308 G/A and -238 G/A, in patients with sporadic colon adenocarcinoma in order to investigate the possible role of these SNPs in susceptibility to sporadic colon cancer. Another aim of this study was to examine the influence of TNFα SNPs on TNFα mRNA and protein expression in colon tumors and their possible role in the development and progression of this type of tumor.
  
  
  RESULTS
  The distribution of all four TNFα SNP genotypes in patients showed no significant difference compared to controls. No statistically significant difference in TNFα mRNA expression in tumors and corresponding normal mucous tissue was found (p=0.14). A statistically significant (p=0.028) difference was found in TNFα mRNA expression between histological grade 1 and histological grade 2 and 3 tumors. Additionally, a statistically significant correlation (p=0.03) was found between TNFα-857 C/T genotypes and TNFα mRNA expression in tumor tissue. TNFα mRNA expression was significantly higher in the tumor tissue of patients with -857 CT and -857 TT genotypes. Most of the tumors (78.26%) were positive for TNFα protein. No correlation was found between the TNFα protein expression and clinicopathological characteristics as well as TNFα genotypes. However, patients with TNFα protein negative tumors had longer survival but the result was not statistically significant (p=0.365).
  
  
  CONCLUSIONS
  Our results suggest the role of TNFα as one of the immunomodulatory genes in the progression of sporadic colon cancer.
authors.affiliation: Laboratory for Personalized Medicine, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia. Electronic address: kapitan@irb.hr.
authors.forename: Sanja
authors.initials: S
authors.lastname: Kapitanović
authors.affiliation: Laboratory for Personalized Medicine, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Čačev
authors.affiliation: Laboratory for Personalized Medicine, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia.
authors.forename: Tina
authors.initials: T
authors.lastname: Catela Ivković
authors.affiliation: Department of Surgery, Clinical Hospital Dubrava, Avenija Gojka Šuška 6, 10000 Zagreb, Croatia.
authors.forename: Božo
authors.initials: B
authors.lastname: Lončar
authors.affiliation: Department of Clinical Pathology, Clinical Hospital Dubrava, Avenija Gojka Šuška 6, 10000 Zagreb, Croatia; School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia.
authors.forename: Gorana
authors.initials: G
authors.lastname: Aralica
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D063646:Carcinogenesis / Q000235:genetics; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
keywords: Colon cancer; Immunohistochemistry; SNPs; TNFα; mRNA