Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with B-cell chronic lymphocytic leukemia in the Polish population

Abnormal expression of the costimulatory molecules cytotoxic T-Lymphocyte antigen 4 (CTLA-4), CD28, and inducible co-stimulator (ICOS) leads to disturbances of immune response and an increased risk of cancer. An extended study was undertaken to evaluate the association among the polymorphisms CTLA-4c.49A > G, CTLA-4g.319C > T, CTLA-4g. *642AT(8_33), CD28c. 17+3T > C, and ICOSc. 1554+4GT(8_15) and susceptibility to B-cell chronic Lymphocytic leukemia (B-CLL) in the Polish population. The study revealed increased frequency of the CTLA-4g.319C > T[T] allele and the CTLA-4g.319C > T [T] phenotype in B-CLL patients compared with healthy controls (p = 0.003, odds ratio [OR] = 1.73; and p = 0.009, OR = 1.74, respectively). The presence of the CD28c. 17+3T > C [C] allele and the CD28c. 17+3T > C [C] phenotype increased the OR of B-CLL to 1.59 (p = 0.007) and 1.74 (p = 0.007), respectively. Either CTLA-4g.319C > T or CD28c. 17+3T > C was associated with time to Rai stage progression. The distributions of the alleles and genotypes of the ICOS gene significantly differed between patients and controls (p = 0.0009 and p = 0.006, respectively). Individuals possessing short alleles were 2.02 times more prone to B-CLL than others (p = 0.001), whereas carriers of tong alleles were protected from B-CLL (p = 0.02, OR = 0.62). The haplotype association study and multivariate analysis confirmed the association of CTLA-4g.319C > T and ICOSc. 1554+4GT(815) gene polymorphisms with B-CLL. The polymorphic sites CTLA-4c.49A > G and CTLA-43.*642AT(8_33) did not correlate with B-CLL. Our results are the first in the literature to report that gene polymorphism of the costimulatory molecules CTLA-4, CD28, and]COS contributes to susceptibility to B-CLL. (c) 2008 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.