Investigation of some gene polymorphisms thought to be associated with prostate cancer in Turkish patients

Prostate cancer is the second most common cancer type in men throughout the world. It is the second cause of death because of cancer among men in Turkey. Prostate cancer is often asymptomatic at early stages of the disease and occurrence of symptoms indicates the progression of disease or metastasis formation. A direct cause of prostate cancer has not been identified, but a number of risk factors such as age, hereditary predisposition, smoking and alcohol consumption, diet, race and genetical factors have been identified. Single nucleotide polymorphism (SNP) is a variation of one nucleotide sequence at any region of genome that may cause disease susceptibility. Therefore, SNPs have been proposed as ideal markers in disease association studies. As a result of these studies that were performed in case and control groups from various populations, multiple SNPs associated with prostate cancer have been identified. It is known that different populations may have different sets of risk alleles, thus SNP profiles of each population must be defined, separately. The main purpose of this thesis study was to associate 67 SNPs with prostate cancer which were previously reported to be associated with prostate cancer in different societies, by investigating SNPs in prostate cancer and healthy control subjects. In this study, genotyping of 67 SNPs was performed in 175 samples (85 patients, 90 controls) by iPLEX method. Hardy Weinberg Equilibrium was tested for each of 67 SNPs and it is obtained that rs11135910, rs11902236, rs445114, rs721048, rs6497287 and rs6983267 genotype frequencies significantly differed from HWE (p≤0,05). The association of SNP alleles and prostate cancer was investigated and rs1016343 (OR=1,91; 95% CI=1,12-3,26; p=0,017), rs1456315 (OR=2,40; 95% CI=1,22-4,72; p=0,011), rs10896449 (OR=1,54; 95% CI=1,00-2,37; p=0,047), rs3771570 (OR=2,07; 95% CI=1,04-4,14; p=0,039), rs7141529 (OR=1,61; 95% CI=1,05-2,46; p=0,029) and rs684232 (OR=1,61; 95% CI=1,03-2,51; p=0,038) variants were determined to be statistically associated with prostate cancer with the highest odds ratio (OR) values. The genotypes of rs1016343 (OR=1,90; 95% CI=1,01-3,57; p=0,046), rs7141529 (OR=2,31; 95% CI=1,01-5,27; p=0,046) and rs684232 (OR=1,83; 95% CI=0,10-3,36; p=0,05) were found to have the highest OR values and determined to be statistically associated with prostate cancer. Associations between genotypes of SNPs and clinico-pathological variables were also investigated and SNPs that found to be statistically associated with age were rs1218582 and rs3850699; with family history of cancer was rs5945572; with family history of prostate cancer were rs5945572 and rs7931342; with Gleason score were rs1571801 and rs7611694; with smoking were rs9623117, rs10896449, rs1270884; with alcohol was rs1270884 (p≤0,05). In this study, the large number of SNPs have been associated with prostate cancer for the first time in Turkish population and these results may pave the way for further biomarker studies that can be used in detecting possible genetic risk of disease in our population.