The possible role of the tumour necrosis factor polymorphisms and human leucocyte antigens in the development of prostate cancer.
The cause of prostate cancer (PC), one of the most common cancers found among ageing men, remains unclear, but genetic predisposition is believed to play a major role in its aetiology. The aim of the study was to examine HLA genes polymorphism and TNF polymorphisms in PC development. Patients diagnosed with PC (N = 113) and 150 healthy individuals were tested for HLA-A, HLA-B and HLA-DRB1 genes and for TNFa, TNFb and TNFd microsatellites. The comparison of patients and controls revealed a positive association of HLA-DRB1*12, TNFa2 and TNFb5, and a negative association of HLA-DRB1*13 and TNFb4 with PC. A division of patients into groups according to age, pre-operative PSA level, Gleason score (GS) and involvement of prostatic capsule, seminal vesicles or bladder neck and perineural invasion of PC demonstrated the following: a positive correlation of HLA-DRB1*12 and a negative correlation of HLA-DRB1*13 with younger patients (<65 years), GS > 7 and the positive association of prostatic capsule, seminal vesicles, bladder neck and perineural invasion of PC; TNFb4 allele's negative association with older patients displaying higher PSA levels, higher GS and positive surrounding tissue involvement; positive association of TNFb5 allele for both older and younger patients. Investigation of HLA genes and TNF microsatellites demonstrated a possible role of HLA-DRB1 and TNF regions in PC aetiology.
Clinical Unit for Tissue Typing, Clinical Department for Transfusion Medicine and Transplantation Biology, University Hospital Centre Zagreb, Zagreb, Croatia.
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Stingl Jankovic
Clinical Department of Urology, University Hospital Centre Zagreb, Zagreb, Croatia.
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Hudolin
Clinical Department of Urology, University Hospital Centre Zagreb, Zagreb, Croatia.
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Kastelan
Clinical Unit for Tissue Typing, Clinical Department for Transfusion Medicine and Transplantation Biology, University Hospital Centre Zagreb, Zagreb, Croatia.
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R
Zunec
Clinical Unit for Tissue Typing, Clinical Department for Transfusion Medicine and Transplantation Biology, University Hospital Centre Zagreb, Zagreb, Croatia.
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Grubic
D000368:Aged; D000369:Aged, 80 and over; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D059811:HLA-DRB1 Chains; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D017430:Prostate-Specific Antigen