title: Association of T-cell regulatory gene polymorphisms with oral squamous cell carcinoma.
abstract: Costimulatory molecules have complementary effects on T-cell activation and their balance may control the development of oral cancer. The aim of this study was to determine the relevance of cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD28 and inducible costimulator (ICOS) polymorphisms in oral squamous cell carcinoma (OSCC). Genotyping for CTLA-4 (-1661 A/G and +49 A/G), CD28 (0 C/G and +3160 G/T) and ICOS (+637 A/C and +1599 C/T) was performed in the 83 patients with OSCC, compared to the 40 unrelated healthy volunteers as controls. The genotype CTLA-4 -1661 was significantly different between the patient group and the control group. The allele CTLA-4 -1661 G was significantly found more frequent in patients with OSCC (p=0.001). In bivariate analysis, noticeable differences between OSCC and controls were seen. The combinations CTLA-4 -1661 G/G and CTLA-4 +49 A/G, ICOS +1559 C/T and ICOS +1559 C/C each with CTLA-4 -1661 G/G, ICOS +637 C/C and ICOS +637 A/C each with CTLA-4 -1661, CTLA-4 -1661 A/G and ICOS +637 C/C, CD28 +3160 G/T and CTLA-4 -1661 A/A and CD28 +3160 G/T and CTLA-4 -1661 A/G were seen in the patient group only. Especially the polymorphisms of the CTLA-4 -1661-genotype - alone and in combination with other T cell regulator polymorphisms - seem to be possible predisposing factors for OSCC. Therefore, they might be future targets for a primary prophylaxis or an individualised therapy.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Peer W
authors.initials: PW
authors.lastname: Kämmerer
authors.forename: Takeshi
authors.initials: T
authors.lastname: Toyoshima
authors.forename: Fabian
authors.initials: F
authors.lastname: Schöder
authors.forename: Philipp
authors.initials: P
authors.lastname: Kämmerer
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kuhr
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brieger
authors.forename: Bilal
authors.initials: B
authors.lastname: Al-Nawas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D060908:CTLA-4 Antigen; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human