Is the Genetic Background of Co-Stimulatory CD28/CTLA-4 Pathway the Risk Factor for Prostate Cancer?

• Published in: Pathology oncology research Vol. 23; no. 4; pp. 837 - 843
• Main Authors: Karabon, Lidia, Tupikowski, K., Tomkiewicz, A., Partyka, A., Pawlak-Adamska, E., Wojciechowski, A., Kolodziej, A., Dembowski, J., Zdrojowy, R., Frydecka, I.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-10-2017; Springer Nature B.V
• Subjects: Alleles; Biomedical and Life Sciences; Biomedicine; Cancer Research; CD28 antigen; CD28 Antigens - genetics; Cell activation; CTLA-4 Antigen - genetics; CTLA-4 protein; Deregulation; Genetic diversity; Genetic Predisposition to Disease - genetics; Genotype; Genotypes; Haplotypes; Health risks; Humans; Immune response; Immunology; Lymphocytes T; Male; Middle Aged; Oncology; Original Article; Pathology; Polymorphism; Polymorphism, Single Nucleotide; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - immunology; Risk assessment; Risk Factors; Single-nucleotide polymorphism; Susceptibility; CD28; Gene polymorphisms; CTLA-4; Prostate cancer
• ISSN: 1219-4956; 1532-2807
• DOI: 10.1007/s12253-016-0180-4

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-4
c.49A>G[A] allele and carriers of
CTLA-4
g.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-4
c.49A>G and
CTLA-4
g.319C>T SNPs might be considered as low risk susceptibility
locus
for PCa.