Two Susceptibility Loci Identified for Prostate Cancer Aggressiveness
نویسندگان
چکیده
Most men diagnosed with prostate cancer will experience indolent disease; hence, discovering genetic variants that distinguish aggressive from nonaggressive prostate cancer is of critical clinical importance for disease prevention and treatment. In a multistage, case-only genome-wide association study of 12,518 prostate cancer cases, we identify two loci associated with Gleason score, a pathological measure of disease aggressiveness: rs35148638 at 5q14.3 (RASA1, P=6.49 × 10(-9)) and rs78943174 at 3q26.31 (NAALADL2, P=4.18 × 10(-8)). In a stratified case-control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P=8.85 × 10(-5)) with no association for nonaggressive prostate cancer compared with controls (P=0.57). The proximity of these loci to genes involved in vascular disease suggests potential biological mechanisms worthy of further investigation.
منابع مشابه
Heterogeneity of genetic alterations in prostate cancer: evidence of the complex nature of the disease.
Prostate cancer is a complex, multifactorial disease with genetic and environmental factors involved in its etiology. The search for genetic determinants involved in the disease has proven to be challenging, in part because such complex diseases are often not amenable to characterization by linkage analysis and positional cloning as is the case for diseases with simple Mendelian genetic inherit...
متن کاملBiology of Human Tumors The Prostate Cancer Susceptibility Variant rs2735839 Near KLK3 Gene Is Associated with Aggressive Prostate Cancer and Can Stratify Gleason Score 7 Patients
Purpose:Gleason score (GS) 7 prostate cancer is a heterogeneous diseasewith different clinical behavior. We sought to identify genetic biomarkers that may predict the aggressiveness of GS 7 diseases. Experimental Design:We genotyped 72 prostate cancer susceptibility SNPs identified in genome-wide association studies in 1,827 white men with histologically confirmed prostate adenocarcinoma. SNPs ...
متن کاملEndothelin-1 expression in prostate needle biopsy specimens correlated with aggressiveness of prostatic cancer
Background & Objective: As the prostate adenocarcinoma is one of the most common malignant tumors in males, looking for a marker to effectively predict aggressiveness and metastatic potential in an apparently localized cancer in initial needle biopsy specimens can help the clinicians to make more appropriate decision for treatment, planning, and choosing appropriate ta...
متن کاملSNP-SNP Interaction Network in Angiogenesis Genes Associated with Prostate Cancer Aggressiveness
Angiogenesis has been shown to be associated with prostate cancer development. The majority of prostate cancer studies focused on individual single nucleotide polymorphisms (SNPs) while SNP-SNP interactions are suggested having a great impact on unveiling the underlying mechanism of complex disease. Using 1,151 prostate cancer patients in the Cancer Genetic Markers of Susceptibility (CGEMS) dat...
متن کاملLarge-scale association analysis in Asians identifies new susceptibility loci for prostate cancer
Genome-wide association studies (GWAS) have identified ∼100 genetic loci associated with prostate cancer risk. Less than a dozen of these loci were initially identified from GWAS in two Asian populations, likely because of smaller sample sizes of these individual GWAS in Asians. Here, we conduct a large-scale meta-analysis of two GWAS from the Japanese population (1,583 cases and 3,386 controls...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 6 شماره
صفحات -
تاریخ انتشار 2015