title: CTLA-4, CD28, and ICOS gene polymorphism associations with non-small-cell lung cancer.
abstract: Polymorphisms in genes encoding CD28, ICOS, and CTLA-4 were demonstrated to be associated with susceptibility to malignancies. To the best of our knowledge, no study on this association has been performed in a Caucasian population for non-small-cell lung cancer (NSCLC). In the present work, we investigated the polymorphisms CTLA-4c.49A>G (rs231775), CTLA-4g.319C>T (rs5742909), CTLA-4g.*642AT(8_33), CTLA-4g.*6230G>A (CT60) (rs3087243), CTLA-4g.*10223G>T (Jo31) (rs11571302), CD28c.17+3T>C (rs3116496), and ICOSc.1554+4GT(8_15) in 208 NSCLC patients and 326 controls. The distributions of the allele and genotype were similar in both groups for CTLA-4, CD28, and ICOS gene polymorphisms. However, we noted a tendency toward overrepresentation of individuals possessing the CTLA-4c.49A>G[A] allele in NSCLC patients compared with controls (0.84 vs 0.79, p = 0.09). The association became significant compared with controls in women for the CTLA-4c.49A>G[A] allele and CTLA-4c.49A>G[AA] genotype (0.67 vs 0.54, p = 0.01, and 0.47 vs 0.30, p = 0.02; respectively). Moreover, the constellation of alleles CTLA-4c.49A>G[A]/CT60[G]/CD28c.17+3T>C[T]/ICOSc.1554+4GT(8_15)[>10] increased the risk of NSCLC about 2-fold (p = 0.002). The same constellation of alleles combined with smoking, CTLA-4g.319C>T[T], and ICOSc.1554+4GT(8_15)[>10] was associated with a decreased overall survival rate. In conclusion, the constellation of specific alleles in CTLA-4, CD28, and ICOS genes contributes to the susceptibility and clinical course of NSCLC.
authors.affiliation: Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wroclaw, Poland. lkarabon@iitd.pan.wroc.pl
authors.forename: Lidia
authors.initials: L
authors.lastname: Karabon
authors.forename: Edyta
authors.initials: E
authors.lastname: Pawlak
authors.forename: Anna
authors.initials: A
authors.lastname: Tomkiewicz
authors.forename: Anna
authors.initials: A
authors.lastname: Jedynak
authors.forename: Ewa
authors.initials: E
authors.lastname: Passowicz-Muszynska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Zajda
authors.forename: Anna
authors.initials: A
authors.lastname: Jonkisz
authors.forename: Renata
authors.initials: R
authors.lastname: Jankowska
authors.forename: Maciej
authors.initials: M
authors.lastname: Krzakowski
authors.forename: Irena
authors.initials: I
authors.lastname: Frydecka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D018106:CD28 Antigens / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics*; D008175:Lung Neoplasms; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking; D015996:Survival Rate
chemical_list: D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein