title: Is the Genetic Background of Co-Stimulatory CD28/CTLA-4 Pathway the Risk Factor for Prostate Cancer?
abstract: The impairment of immunological surveillance caused by aberrant T cell activation can lead to an inadequate anti-tumor response. Therefore, deregulation in co-stimulatory pathway might be associated with cancer susceptibility. Here we undertook a prospective study to investigate whether genetic variations in gene encoding molecule CD28 and CTLA-4 playing pivotal role in regulating adoptive immune response can influence susceptibility to prostate cancer. Single nucleotide polymorphisms (SNPs) in CTLA-4 and CD28 genes were genotyped in 301 prostate cancer (PCa) patients and 301 controls. The distributions of the genotypes and haplotypes in the CTLA-4/CD28 SNPs were similar in both studied groups. However, the overrepresentation of carriers of CTLA-4c.49A>G[A] allele and carriers of CTLA-4g.319C>T[T] allele in PCa as compared to controls was observed (p = 0.082 and p = 0.13, respectively). The risk of disease was higher (OR 1.78) for carriers of both susceptibility alleles as compared to carriers of protective genotypes (p = 0.03). The CTLA-4c.49A>G and CTLA-4g.319C>T SNPs might be considered as low risk susceptibility locus for PCa.
authors.affiliation: Department of Urology and Oncological Urology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland. lkarabon@iitd.pan.wroc.pl.|Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Weigla 12, 53-114, Wroclaw, Poland. lkarabon@iitd.pan.wroc.pl.
authors.forename: Lidia
authors.identifier: http://orcid.org/0000-0001-8172-0971
authors.initials: L
authors.lastname: Karabon
authors.affiliation: Department of Urology and Oncological Urology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland.|Department of Oncologic Urology, Lower Silesian Oncology Center, pl. Hirszfelda 12, Wroclaw, 53-413, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Tupikowski
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Tomkiewicz
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Partyka
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Pawlak-Adamska
authors.affiliation: Department of Urology and Oncological Urology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Wojciechowski
authors.affiliation: Department of Urology and Oncological Urology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Kolodziej
authors.affiliation: Department of Urology and Oncological Urology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Dembowski
authors.affiliation: Department of Urology and Oncological Urology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Zdrojowy
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: I
authors.initials: I
authors.lastname: Frydecka
mesh_terms: D018106:CD28 Antigens / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology*; D012307:Risk Factors
chemical_list: D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human
keywords: CD28; CTLA-4; Gene polymorphisms; Prostate cancer