| Abstract | Cilj istraživanja Angiogeneza ima važnu ulogu u razvoju, rastu i širenju solidnih tumora pa tako i karcinoma prostate. Brojna istraživanja povezuju potencijalno funkcionalne polimorfizme jedne baze u genima važnim za agiogenezu u prostati s povećanim rizikom i agresivnijim oblikom karcinoma prostate. Cilj ovog istraživanja bio je ispitati utjecaj polimorfizama IL-1fi, IL-8 i VEGF gena proangiogenih citokina na nastanak i razvoj agresivnijeg oblika karcinoma prostate. Ispitanici i metode Prospektivno istraživanje parova obuhvatilo je 275 ispitanika s područja istočne Hrvatske: 120 s karcinomom prostate, 120 s benignom hiperplazijom prostate i 35 zdravih kontrola. Svakom ispitaniku je nakon uzimanja anamneze učinjen digitorektalni pregled (DRP) i izuzeta krv za analizu prostata specifičnog antigena (PSA) i analizu polimorfizama gena. Ispitanici s pozitivnim DRP-om i/ili povišenim PSA-om podvrgnuti su biopsiji. Svaki ispitanik dao je pismeni pristanak za sudjelovanje u ispitivanju nakon upoznavanja s načinom provođenja i svrhom ispitivanja. Koncentracija PSA određena je elektrokemiluminiscentnim testom, a genotipizacija je rađena metodom lančane reakcije polimerazom u stvarnom vremenu. Rezultati Polimorfizam IL-1fi gena bio je značajno učestaliji kod bolesnika s BHP-om i karcinomom prostate u odnosu na zdravu populaciju (P = 0,001). Bolesnici s karcinomom prostate imali su učestaliji polimorfni TT genotip i T alel od BHP skupine uz graničnu statističku značajnost (x = 1,77; p = 0,061) s većim rizikom za nastanak karcinoma (OR 2,02; CI 95 % 0,84 - 4,86) uz TT genotip. Analizom međudjelovanja polimorfizama s etiološkim čimbenicima nađena je povezanost nasljednog oblika karcinoma (OR 8,83; CI 95 % 1,09 - 71,58 za T alel) i pretilosti (OR 3,68; CI 95 % 1,29 - 10,5 za CT genotip) s rizikom za nastanak karcinoma prostate uslijed polimorfizma IL-1fi gena. Zapaža se povećana učestalost IL-8 -251 AA genotipa kod bolesnika s karcinomom prostate i BMI > 30, iako nije dostignuta statistička značajnost (P = 0,093). Ispitanici s BHP-om, pušači imaju učestaliji polimorfni IL- 8 alel/genotip (P = 0,057 za AA genotip; P = 0,057 za A alel). Nije nađena povezanost 87 polimorfnih alela/genotipova ispitivanih gena citokina s agresivnijim oblikom karcinoma prostate niti sa serumskim vrijednostima PSA. Zaključak Na temelju rezultata ovog istraživanja može se zaključiti da specifični polimorfizmi IL- 1P i IL-8 gena potencijalno mijenjaju sklonost obolijevanju od karcinoma prostate u našoj populaciji, odnosno potvrđuju značaj angiogeneze u etiopatogenezi karcinoma prostate. |
| Abstract (english) | Angiogenesis plays an important role in the development, growth and spread of solid tumors, including prostate cancer. Numerous studies link potentially functional single nucleotide polymorphisms (SNP) in genes important in prostate agiogenesis with increased risk and aggressive form of prostate cancer. The aim of this study was to investigate the influence of polymorphisms in the IL-1fi, IL-8 and VEGF pro angiogenic cytokine genes on the development, growth and progression to more aggressive form of prostate cancer. Participants and methods A prospective case control study included 275 participants from the eastern Croatia: 120 with prostate cancer, 120 with benign prostatic hyperplasia and 35 healthy controls. All participants underwent digital rectal examination (DRE) and blood sampling for prostate specific antigen (PSA) determination and the analysis of polymorphisms of interest. Patients with positive DRE and/or elevated PSA underwent prostate biopsy. Each subject gave written informed consent form to participate in the study after having been acquainted with the manner and purpose of conducting tests. PSA concentration was determined by electrochemiluminescent assay and genotyping was performed by polymerase chain reaction in real time. Results Polymorphism of IL-1fi gene was significantly more frequent in patients with BHP and prostate cancer compared to healthy controls (P=0.001). Patients with prostate cancer had more common polymorphic TT genotype and T allele than the BHP group with borderline statistical significance (%2=1.77; P=0.061) and with a higher risk of cancer development (OR 2.02; 95% CI 0,84- 4.86) with the TT genotype. By analyzing the interactions between polymorphisms with etiologic factors we found correlation of hereditary forms of cancer (OR 8.83; CI 95% 1.09 to 71.58 for the T allele) and obesity (OR 3,68; CI 95% 1,29-10,5 for the CT genotype) with a risk of prostate cancer due to polymorphism of the IL-1fi gene. It is noted an increased frequency of IL-8 -251 AA genotype in patients with prostate cancer and BMI>30, although with no statistical significance (P=0.093). BHP subjects, smokers have 89 more frequent polymorphic IL-8 allele/genotype (P=0.057 for the AA genotype; P=0.057 for the A allele). There was no correlation of polymorphic alleles/genotypes examined cytokine genes with a more aggressive form of prostate cancer, nor with serum PSA values. Conclusion In conclusion, this study suggests that the specific polymorphisms of IL-1fi and IL-8 gene potentially increase susceptibility to prostate cancer development in our population and confirms the importance of angiogenesis in pathogenesis of prostate cancer. |
