title: CTLA-4 and CD28 genes' polymorphisms and renal cell carcinoma susceptibility in the Polish population--a prospective study.
abstract: Polymorphisms in co-stimulatory genes are associated with susceptibility to several malignances such as breast cancer, cervical cancer and chronic lymphocytic leukemia, but have been scarcely investigated in renal cell cancer (RCC). A total of 310 RCC patients and 518 controls were genotyped for single-nucleotide polymorphisms (SNPs) in the CTLA-4 and CD28 genes: CTLA-4c.49A>G (rs231775), CTLA-4g.319C>T (rs5742909), CTLA-4g.*6230G>A (CT60; rs3087243), CTLA-4g.*10223G>T (Jo31; rs11571302), CD28c.17+3T>C (rs3116496) and CD28c.-1042G>A (rs3181098). The distribution of the alleles, genotypes and haplotypes in the CTLA-4 and CD28 genes were similar in the RCC patients and in the controls. However, among the patients with a clear cell RCC (CCRCC), the G allele carriers of CT60 and Jo31 SNPs were overrepresented, and the overrepresentation became significant for the carriers of CT60[G] allele in CCRCC patients with necrosis in the primary tumor (P = 0.046). The CTLA-4c.49A>G[A]/CTLA-4g.319C>T[C]/CT60[A]/Jo31[T]/CD28c.17+3T>C[T]/ CD28c.1042G>A[G] haplotype was associated with an approximately threefold increased risk of primary tumor necrosis in CCRCC patients (P corrected = 0.0000007) and with the advanced stage of disease (IV) (P corrected = 0.001). When stratified by gender, CD28c.-1042G>A[GG] genotype was more frequent in the female CCRCC patients compared with healthy women (P = 0.042). Polymorphisms in the CTLA-4 and CD28 genes, in particular considered together as haplotypes, were associated with increased risk of CCRCC, especially with necrosis and with the advanced stage of disease. The CD28c.-1042G>A SNP modulates the risk of CCRCC in women. These findings indicate that the associations of the CTLA-4 and CD28 polymorphisms with the risk of renal cancer are worth further study in a larger group of patients.
authors.affiliation: Department of Urology and Oncological Urology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Tupikowski
authors.affiliation: Department of Experimental Therapy, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Partyka
authors.affiliation: Department of Urology and Oncological Urology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Kolodziej
authors.affiliation: Department of Urology and Oncological Urology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Dembowski
authors.affiliation: Department of Urology and Oncological Urology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Debinski
authors.affiliation: Division of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Halon
authors.affiliation: Department of Urology and Oncological Urology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Zdrojowy
authors.affiliation: Department of Experimental Therapy, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: I
authors.initials: I
authors.lastname: Frydecka
authors.affiliation: Department of Urology and Oncological Urology, Wroclaw Medical University, Wroclaw, Poland.|Department of Experimental Therapy, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: L
authors.initials: L
authors.lastname: Karabon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018106:CD28 Antigens / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012737:Sex Factors
chemical_list: D018106:CD28 Antigens; D060908:CTLA-4 Antigen
keywords: CD28; CTLA-4; polymorphisms; renal cancer