Evaluation of homeobox protein B13 (hoxb13) gene g84e mutation in patients with prostate cancer.

Prostate cancer (PCa) is a disease that is increasingly common today, and with innovations in diagnosis and treatment, it can be completely cured when localized. For early diagnosis and screening purposes, it is strongly recommended in guidelines to perform a prostate-specific antigen (PSA) test for men over 45 years of age who are at high risk and over 50 years of age for others. The incidence, diagnosis, and treatment of PCa are associated with the increase in the availability of PSA testing. In recent years, many clinical studies have focused on potential mutations that may be associated with the genetic background of PCa. In the literature, the Homeobox Protein B13 (HOXB13) gene has been identified as one of the genes that may be a risk factor for PCa development due to certain mutations. One of the rare but thought to play a role in the pathophysiology of PCa is the HOXB13 gene G84E (rs138213197) mutation. Although many different mechanisms explaining the role of HOXB13 protein in PCa formation have been proposed, a consensus on a specific mechanism has not yet been reached. According to current molecular data, it is believed that the G84E variant changes the interaction between the HOXB13 protein and MEIS proteins, thereby contributing to PCa development. Our study aims to prospectively evaluate the relationship between PCa and the HOXB13 gene G84E mutation in the Turkish population. The study included 150 patients diagnosed with PCa and 150 control subjects diagnosed with benign prostatic hyperplasia (BPH) who applied to the Department of Urology at Mersin University Medical Faculty. Demographic and clinical data were prospectively examined and recorded from the patients. DNA isolation from blood samples, collected in EDTA tubes from patients who consented to participate in the study and stored at +4°C, was performed using a DNA isolation kit (Roche Diagnostics, GmbH, Mannheim, Germany). The analysis of the HOXB13 gene G84E mutation (rs138213197) in the obtained DNA samples was carried out using an RT-PCR instrument (Roche Diagnostics LightCycler 480, GmbH, Mannheim, Germany). Data encoding and statistical analyses were conducted using the SPSS 22 software package (IBM SPSS Statistics, IBM Corporation, Chicago, IL). The pathological allele of the HOXB13 gene G84E mutation was T. According to the findings obtained, while no mutation was detected in any of the control group, 17 patients in the patient group were found to have the G84E mutation, all in the TC genotype. According to the analysis, having the CC genotype was found to reduce the risk of prostate cancer by 0.47 times (OR=0.47, CI=0.415-0.532). While according to literature data, it is known that early diagnosis age and a family history of PCa increase the risk of carrying the G84E variant, in our analyses, no significant difference was found in terms of diagnosis age and family history of PCa between the group carrying the mutation and the group not carrying it. However, the carrier status of the G84E mutation was observed to be relatively higher in individuals with a positive family history. On the other hand, all patients diagnosed with oligometastatic disease were in the group not carrying the HOXB13 gene G84E mutation (% 22.6 vs. % 0, p<0.001). There was no relationship between clinical features such as ISUP grade, NCCN risk classification, diagnosis PSA, TNM stage, and the G84E mutation. In recent years, the HOXB13 protein, which is an important molecular and genetic marker investigated for its relationship with PCa, has not been detected in any study conducted on Turkish men with PCa. This enhances the original value of our study. The findings we obtained support the role of the G84E mutation of the HOXB13 gene, which is a known genetic marker associated with PCa in different ethnic backgrounds, in the etiology of PCa in the Turkish population and contribute to the literature data.