ID

45968

Description

Principal Investigator: Sonja Berndt, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA MeSH: Prostatic Neoplasms https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000882 This genome-wide association study was funded by the National Cancer Institute (NCI) to identify uncommon susceptibility loci for prostate cancer. A total of 4,600 prostate cancer cases and 2,840 controls of European ancestry from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were genotyped using the Illumina HumanOmni2.5 and passed rigorous quality control filters. Additional genotype data (available in dbGap under other accession numbers) from 101 independent controls of European ancestry scanned with the HumanOmni2.5 were also included, resulting in a total of 4,600 cases and 2,941 controls for the published analysis. SNPs from the most promising regions, as determined by rank p-value, under multiple different models as well as select candidate genes were taken forward for replication using a custom Iselect chip in 6,575 cases and 6,392 controls of European ancestry. Results from the primary scan after imputation were then meta-analyzed with the Iselect results as well as results from previous GWAS. In a combined meta-analysis of the primary scan together with the custom Iselect replication and a previous GWAS, thirteen loci reached genome-wide significance (P 5 x 10sup-8/sup) for prostate cancer overall; however, each of them confirmed a previously reported locus. Although they did not reach genome-wide significance, we found evidence for two new suggestive loci at chromosome 16q22.2 (PKD1L3, rs12597458, P = 9.67 x 10sup-8/sup) and 6p22.3 (CDKAL1, rs12198220, P = 2.13 x 10sup-7/sup). In a combined case-only analysis of 12,518 prostate cancer cases, we identified two loci associated with Gleason score, a pathological measure of disease aggressiveness: rs35148638 at 5q14.3 (RASA1, P=6.49x10sup-9/sup) and rs78943174 at 3q26.31 (NAALADL2, P=4.18x10sup-8/sup). In a stratified case-control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P=8.85x10sup-5/sup) with no association for non-aggressive prostate cancer compared to controls (P=0.57). Only the cases and controls genotyped on the HumanOmni2.5 specifically for this study are included under this accession number. Controls (n=101) genotyped with the HumanOmni2.5 for another study are posted under a different accession number. Please note that the majority of prostate cancer cases and controls genotyped in CGEMS (and posted under a different accession number) are included in this study.

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dbGaP study=phs000882

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1. 3/26/24 3/26/24 - Madita Rudolph

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Sonja Berndt, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

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March 26, 2024

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