RESUMO
In this study, we have evaluated whether 57 genome-wide association studies (GWAS)-identified common variants for type 2 diabetes (T2D) influence the risk of developing prostate cancer (PCa) in a population of 304 Caucasian PCa patients and 686 controls. The association of selected single nucleotide polymorphisms (SNPs) with the risk of PCa was validated through meta-analysis of our data with those from the UKBiobank and FinnGen cohorts, but also previously published genetic studies. We also evaluated whether T2D SNPs associated with PCa risk could influence host immune responses by analysing their correlation with absolute numbers of 91 blood-derived cell populations and circulating levels of 103 immunological proteins and 7 steroid hormones. We also investigated the correlation of the most interesting SNPs with cytokine levels after in vitro stimulation of whole blood, peripheral mononuclear cells (PBMCs), and monocyte-derived macrophages with LPS, PHA, Pam3Cys, and Staphylococcus Aureus. The meta-analysis of our data with those from six large cohorts confirmed that each copy of the FTOrs9939609A, HNF1Brs7501939T, HNF1Brs757210T, HNF1Brs4430796G, and JAZF1rs10486567A alleles significantly decreased risk of developing PCa (p = 3.70 × 10-5, p = 9.39 × 10-54, p = 5.04 × 10-54, p = 1.19 × 10-71, and p = 1.66 × 10-18, respectively). Although it was not statistically significant after correction for multiple testing, we also found that the NOTCH2rs10923931T and RBMS1rs7593730 SNPs associated with the risk of developing PCa (p = 8.49 × 10-4 and 0.004). Interestingly, we found that the protective effect attributed to the HFN1B locus could be mediated by the SULT1A1 protein (p = 0.00030), an arylsulfotransferase that catalyzes the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. In addition to these results, eQTL analysis revealed that the HNF1Brs7501939, HNF1Brs757210, HNF1Brs4430796, NOTCH2rs10923931, and RBMS1rs7593730 SNPs influence the risk of PCa through the modulation of mRNA levels of their respective genes in whole blood and/or liver. These results confirm that functional TD2-related variants influence the risk of developing PCa, but also highlight the need of additional experiments to validate our functional results in a tumoral tissue context.
RESUMO
OBJECTIVES: The advances of minimally invasive surgery in urology over the last years have enabled a progressive and constant implementation of endourology and laparoscopy in pediatric patients. We perform a review of our experience, as a general hospital, with minimally invasive surgery performed in pediatric patients over the last ten years. METHODS: We retrospectively analyzed the endourological and laparoscopic operations performed between 1997 and 2007 in children up to the age of 16 years, collecting data about patient's age and gender, type of disease, techniques, anesthesia, and perioperative events. RESULTS: seventy-two surgical operations were performed in patients with an age range between 28 days and 16 years, with a mean age of 6.8 years. 56% of the patients were boys and 44% girls. Indications for surgery was vesicoureteral reflux (VUR) in 28 cases (38.8%); lithiasis 17 cases (23.6%) which were distributed in 4 cystolithotripsies, 9 ureterorenoscopy with lithotripsy, one pure percutaneous nephrolithotomy and three mixed; ureterocele 9 cases (12.5%); urethral obstruction 7 cases (9.7%); 3 diagnostic laparoscopies for cryptorchidism (4. 1%), 2 laparoscopic procedures for cystic pathology (2.7%), another 2 laparoscopic renal biopsies (2.7%), and one laparoscopic repair of a ureteropyelic junction syndrome; 1 case of emergency percutaneous nephrostomy in the supine position after open pyeloplasty with subsequent reoperation with percutaneous resection of a granuloma; and 1 case of botulin toxin injection into the detrusor muscle. CONCLUSIONS: The consolidation of pediatric endourology in our department, and more recently laparoscopy, has contributed to improve the quality of care in pediatric patients; it has been achieved thanks to our previous know-how in general endourological techniques and the existence of adequate technical and human resources.
