Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) that mildly predict prostate cancer risk. These SNPs are local tagging markers for causal gene alterations. Consideration of candidate genes in the tagged regions would be facilitated by additional information on the particular pathomechanisms which contribute to the observed risk increase. In this study we test for an association of prostate cancer tagging SNPs with alterations in DNA repair capacity, a phenotype that is frequently involved in cancer predisposition. DNA repair capacity was assessed on blood lymphocytes from 128 healthy probands after ionizing irradiation. We used the micronucleus (MN) assay to determine the cellular DNA double-strand break repair capacity and flow cytometry to measure damage induced mitotic delay (MD). Probands were genotyped for a panel of 14 SNPs, each representing an independent prostate cancer risk locus previously identified by GWAS. Associations between germline variants and DNA repair capacity were found for the SNPs rs1512268 (8p21), rs6983267 (8q24) and rs10993994 (10q11). The most significant finding was an association of homozygous rs10993994 T-allele carriers with a lower MN frequency (p=0.0003) and also a decreased MD index (p=0.0353). Cells with prostate cancer risk alleles at rs10993994 seem to cope more efficiently with DNA double strand breaks (less MN) in a shorter time (decreased MD index). This intriguing finding imposes concern about the accuracy of repair, with respect to the cancer risk that is mediated by T genotypes. To date, MSMB (microseminoprotein β) is favored as the causal gene at the 10q11 risk locus, since it was the first candidate gene known to be expressionally altered by rs10993994. Based on the present observation, candidate genes from the contexts of DNA repair and apoptosis may be more promising targets for expression studies with respect to the rs10993994 genotype.
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http://dx.doi.org/10.1016/j.dnarep.2012.05.003 | DOI Listing |
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, , 11829, Cairo, Egypt.
Globally, the incidence and death rates associated with cancer persist in rising, despite considerable advancements in cancer therapy. Although some malignancies are manageable by a mix of chemotherapy, surgery, radiation, and targeted therapy, most malignant tumors either exhibit poor responsiveness to early identification or endure post-treatment survival. The prognosis for prostate cancer (PCa) is unfavorable since it is a perilous and lethal malignancy.
View Article and Find Full Text PDFAsia Pac J Clin Oncol
January 2025
LifeStrands Genomics Australia, Mount Waverley, Victoria, Australia.
Some patients with metastatic castration-resistant prostate cancer (mCRPC) possess germline or acquired defects in the DNA damage repair (DDR) genes BRCA1 and BRCA2. Tumors with BRCA mutations exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi) such as olaparib and rucaparib. As a result, molecular diagnostic testing to identify patients with BRCA mutations eligible for the PARPi therapy has become an integral component of managing patients with mCRPC.
View Article and Find Full Text PDFCancer Med
January 2025
Department of Urology, Queen Elizabeth University Hospital, Glasgow, UK.
Background: To assess how centralisation of cancer services via robotic surgery influenced positive surgical margin (PSM) occurrence and its associated risk of biochemical recurrence (BCR) in cases of pT2 prostate cancer (PC).
Methods: Retrospective analysis of all radical prostatectomy (RP) cases performed in the West of Scotland during the period from January 2013 to June 2022. Primary outcomes were PSM and BCR.
Genome Med
January 2025
Department of Systems Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.
Background: Despite extensive analysis, the dynamic changes in prostate epithelial cell states during tissue homeostasis as well as tumor initiation and progression have been poorly characterized. However, recent advances in single-cell RNA-sequencing (scRNA-seq) technology have greatly facilitated studies of cell states and plasticity in tissue maintenance and cancer, including in the prostate.
Methods: We have performed meta-analyses of new and previously published scRNA-seq datasets for mouse and human prostate tissues to identify and compare cell populations across datasets in a uniform manner.
BMC Public Health
January 2025
Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Gran Via de Les Corts Catalanes, 587 Àtic, 08007, Barcelona, Spain.
This study examines remaining life expectancy (RLE) after a cancer diagnosis, focusing on age, sex, cancer type, and metabolic syndrome (MS) components, using data from the SIDIAP database in Catalonia (2006-2017). RLE was analyzed for 13 cancer types, stratified by sex and MS components. The cohort study includes 183,364 individuals followed from diagnosis until death, transfer, or study end (December 2017).
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