RESUMO
There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.
Assuntos
Predisposição Genética para Doença/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Testes Genéticos , Humanos , Calicreínas/genética , Masculino , Proteínas de Membrana/genética , Proteínas Secretadas pela Próstata/genética , Proteínas Serina-Treonina Quinases/genética , Fatores de RiscoRESUMO
OBJECTIVE: Radical prostatectomy (RP) as a first line treatment of prostate cancer was rare prior to the advent of prostate specific antigen (PSA) testing, yet little is known of its use and outcomes in a population setting. We described baseline characteristics of cases in the Victorian Radical Prostatectomy Register (VRPR), investigated possible associations between demographic characteristics and characteristics at diagnosis and at surgery and trends over time. METHODS: The VRPR is a population-based series of all RPs performed in Victoria from July 1995 to December 2000 (n=2,154). RESULTS: On average, socio-economic status for cases was higher than for the general Victorian population (34% vs 20% in the highest quintile respectively, p<0.0001). The proportion of PSA-detected cases increased from 53% in 1995 to 79% in 2000 (p for linear trend=0.0004). Age at surgery and PSA levels at diagnosis decreased over time (p=0.006 and p=0.04 respectively). The proportion of cases with Gleason score < or =5 from RP decreased from 35% in 1995 to 14% in 2000, while cases with Gleason score 6-7 increased from 60% to 79%. Similar trends were observed for Gleason score from biopsy. We found little evidence of significant trends over time in other pathological characteristics relevant to prognosis. CONCLUSION AND IMPLICATIONS: The VRPR provides a unique whole of population based description of radical prostatectomy in Victoria, confirms findings previously reported in single institution clinical series overseas such as migration to younger age at surgery and to Gleason scores 6 to 7, and provides a resource for evaluating RP outcomes in the future.
Assuntos
Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Antígeno Prostático Específico/isolamento & purificação , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Sistema de Registros , Classe Social , Vitória/epidemiologiaRESUMO
Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at