title: ICOS gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population.
abstract: There is strong evidence that altered immunological function entails an increased risk of B-cell chronic lymphocytic leukemia (B-CLL). The main mechanism of an anti-tumor response depends on T-cell activation. Unlike the constitutively expressed CD28, inducible costimulatory molecule (ICOS) is expressed on the T-cell surface after activation. ICOS enhances all the basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, the upregulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B cells. ICOS is essential for both efficient interaction between T and B cells and normal antibody responses to T cell-dependent antigens. It does not upregulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Our previous results indicated the ICOS gene has a role as a susceptibility locus to B-CLL. Therefore an extended study was undertaken to evaluate the association between four ICOS polymorphisms (which were recently described as functional ones) and susceptibility to B-CLL in the Polish population. A case-control study of 296 individuals, including 146 B-CLL patients, was conducted on four polymorphisms in the ICOS gene. Genotyping of the polymorphisms ICOS ISV1+173T>C (rs10932029), ICOSc.1624C>T (rs10932037), ICOSc.2373G>C (rs4675379), and ICOSc.602A>C (rs10183087) was carried out using allelic discrimination methods with the TaqMan SNP Genotyping Assay. There were no statistically significant differences in the allele, genotype, or haplotype distributions between B-CLL patients and healthy controls for any of the investigated polymorphic markers in the ICOS gene. However, we noted that patients carrying genotype ICOS ISV1+173T>C [TT], ICOSc.602A>C [AA], ICOSc.1624C>T [CC], and ICOSc.2373G>C [GG] have a decreased frequency of progression to a higher Rai stage during 60-month follow-up (21.35% vs. 40.8%, p = 0.013) compared to other individuals. This indicates that the investigated polymorphisms do not modulate the risk of B-CLL in the Polish population, but are associated with disease dynamics, in particular with the time to Rai stage progression.
authors.affiliation: 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: Anna
authors.initials: A
authors.lastname: Jedynak
authors.forename: Anna
authors.initials: A
authors.lastname: Tomkiewicz
authors.forename: Dariusz
authors.initials: D
authors.lastname: Wolowiec
authors.forename: Marek
authors.initials: M
authors.lastname: Kielbinski
authors.forename: Dariusz
authors.initials: D
authors.lastname: Woszczyk
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Kuliczkowski
authors.forename: Irena
authors.initials: I
authors.lastname: Frydecka
mesh_terms: D000368:Aged; D000483:Alleles; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011044:Poland; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein