CTLA-4, CD28 , and ICOS gene polymorphism associations with non-small-cell lung cancer

• Published in: Human immunology Vol. 72; no. 10; pp. 947 - 954
• Main Authors: Karabon, Lidia, Pawlak, Edyta, Tomkiewicz, Anna, Jedynak, Anna, Passowicz-Muszynska, Ewa, Zajda, Katarzyna, Jonkisz, Anna, Jankowska, Renata, Krzakowski, Maciej, Frydecka, Irena
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2011
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Allergy and Immunology; Carcinoma, Non-Small-Cell Lung - epidemiology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - mortality; Case-Control Studies; CD28; CD28 antigen; CD28 Antigens - genetics; CTLA-4; CTLA-4 Antigen - genetics; CTLA-4 protein; Disease Progression; Female; Gene Frequency; Gene polymorphism; Genetic Predisposition to Disease; Genotype; Humans; ICOS; ICOS protein; Inducible T-Cell Co-Stimulator Protein - genetics; Lung cancer; Lung Neoplasms; Male; Malignancy; Middle Aged; Neoplasm Staging; Non-small-cell lung cancer; Poland; Polymorphism, Single Nucleotide; Polymorphisms; Risk Factors; Smoking; Survival; Survival Rate; CD28; Non-small-cell lung cancer; CTLA-4; ICOS; Polymorphisms
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2011.05.010

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 .49 A > G (rs231775), CTLA-4g .319C> T (rs5742909), CTLA-4g. *642 AT(8_33), CTLA - 4 g.*6230G>A (CT60) (rs3087243), CTLA - 4 g.*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 - 4 c.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 - 4 c.49A>G[A] allele and CTLA - 4 c.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 C TLA - 4 c.49A>G[A]/CT60[G]/ CD28 c.17+3T>C[T]/ ICOS c.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 ICOS c.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.