ABSTRACT
PURPOSE: Genetic variations among prostate cancer (PCa) patients who underwent radical prostatectomy (RP) and pelvic lymph node dissection were evaluated to predict lymph node invasion (LNI). Exome arrays were used to develop a clinicogenetic model that combined clinical data related to PCa and individual genetic variations. MATERIALS AND METHODS: We genotyped 242,186 single-nucleotide polymorphisms (SNPs) by using a custom HumanExome BeadChip v1.0 (Illumina Inc.) from the blood DNA of 341 patients with PCa. The genetic data were analyzed to calculate an odds ratio as an estimate of the relative risk of LNI. We compared the accuracies of the multivariate logistic model incorporating clinical factors between the included and excluded selected SNPs. The Cox proportional hazard models with or without genetic factors for predicting biochemical recurrence (BCR) were analyzed. RESULTS: The genetic analysis indicated that five SNPs (rs75444444, rs8055236, rs2301277, rs9300039, and rs6908581) were significant for predicting LNI in patients with PCa. When a multivariate model incorporating clinical factors was devised to predict LNI, the predictive accuracy of the multivariate model was 80.7%. By adding genetic factors in the aforementioned multivariate model, the predictive accuracy increased to 93.2% (p=0.006). These genetic variations were significant factors for predicting BCR after adjustment for other variables and after adding the predictive gain to BCR. CONCLUSIONS: Based on the results of the exome array, the selected SNPs were predictors for LNI. The addition of individualized genetic information effectively enhanced the predictive accuracy of LNI and BCR among patients with PCa who underwent RP.
Subject(s)
Aged , Humans , Male , Middle Aged , Biomarkers, Tumor/genetics , Biopsy , DNA, Neoplasm/genetics , Exome , Gene Frequency , Genome , Genotype , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis , Models, Genetic , Neoplasm Invasiveness , Polymorphism, Single Nucleotide , Predictive Value of Tests , Prospective Studies , Prostatectomy , Prostatic Neoplasms/geneticsABSTRACT
Recently, an increasing number of bisphosphonate related osteonecrosis of the jaw(BRONJ) is being reported. A guideline has been already established in the US, but it does not seem to be fully recognized by clinicians in Korea. Therefore, a survey study was done to inform and have clinicians realize the seriousness of BRONJ. 1,341 practitioners were randomly selected out of 13,405 practitioners(by Feb of 2008, KDA) in Korea. A questionnaire was given to them between May to July in 2008. Questions were designed to investigate each respondent's experience term years in the clinic, occupation, speciality, awareness on risk of bisphosphonate, experience on treating osteonecrosis patients, awareness about the guideline on BRONJ suggested by AAOMS and whether if they ask about bisphosphonate medication history to patients before invasive treatment. 45.1% of the clinicians have reported on experiencing delayed healing on bone exposed site after extraction both in the maxilla and the mandible. However, clinicians have asked the patients whether if they are on bisphosphonate or not in only 15.1% of these cases. 56.5% of the clinicians simply knew about BRONJ but only 28.9% of the clinicians were aware that bisphosphonate can cause osteonecrosis after invasive dental treatment. Only 19.3% knew about the contents of guideline on BRONJ and 57.2% were aware of the seriousness of BRONJ. Clinicians with shorter clinical experience term were more aware of BRONJ and the guideline on BRONJ than the experienced clinicians. But awareness of the possibility of BRONJ after invasive dental treatment were about the same regardless of their clinical experience. The results show that Korean clinicians need to be more aware about BRONJ. Data on BRONJ cases in Korea should be collected and provided with additional education to let Korean clinicians know and be more aware about BRONJ