Elaine A Ostrander

NorthShore University HealthSystem, Chicago, Illinois, United States

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Publications (335)2789.07 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic drivers of clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world. Published by Cold Spring Harbor Laboratory Press.
    Genome Research 07/2015; DOI:10.1101/gr.190314.115 · 13.85 Impact Factor
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    ABSTRACT: Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability of height, and by implication other complex phenotypes. Our overall conclusions are that when study sizes are quite large (5,000 or so) the additive heritability estimate for height is not apparently biased upwards using the linear mixed model; however there is evidence in our simulation that a very large number of causal variants (many thousands) each with very small effect on phenotypic variance will need to be discovered to fill the gap between the heritability explained by known versus unknown causal variants. We conclude that today's GWAS data will remain useful in the future for causal variant prediction, but that finding the causal variants that need to be predicted may be extremely laborious.
    PLoS ONE 06/2015; 10(6):e0131106. DOI:10.1371/journal.pone.0131106 · 3.23 Impact Factor
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    ABSTRACT: 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.
    Nature Communications 05/2015; 6:6889. DOI:10.1038/ncomms7889 · 10.74 Impact Factor
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    ABSTRACT: BACKGROUND Prostate cancer (PCa) is clinically and biologically heterogeneous, making it difficult to predict at detection whether it will take an indolent or aggressive disease course. Cell cycle-regulated genes may be more highly expressed in actively dividing cells, with transcript levels reflecting tumor growth rate. Here, we evaluated expression of cell cycle genes in relation to PCa outcomes in a population-based cohort.METHODS Gene expression data were generated from tumor tissues obtained at radical prostatectomy for 383 population-based patients (12.3-years average follow-up). The overall mean and individual transcript levels of 30 selected cell cycle genes was compared between patients with no evidence of recurrence (73%) and those who recurred (27%) or died (7%) from PCa.RESULTSThe multivariate adjusted hazard ratio (HR) for a change from the 25th to 75th percentile of mean gene expression level (range 8.02–10.05) was 1.25 (95%CI 0.96–1.63; P = 0.10) for PCa recurrence risk, and did not vary substantially by Gleason score, TMPRSS2-ERG fusion status, or family history of PCa. For lethal PCa, the HR for a change (25th to 75th percentile) in mean gene expression level was 2.04 (95%CI 1.26–3.31; P = 0.004), adjusted for clinicopathological variables. The ROC curve for mean gene expression level alone (AUC = 0.740) did not perform as well as clinicopathological variables alone (AUC = 0.803) for predicting lethal PCa, and the addition of mean gene expression to clinicopathological variables did not substantially improve prediction (AUC = 0.827; P = 0.18). Higher TK1 expression was strongly associated with both recurrent (P = 6.7 × 10−5) and lethal (P = 6.4 × 10−6) PCa.CONCLUSIONS Mean expression level for 30 selected cell cycle-regulated genes was unrelated to recurrence risk, but was associated with a twofold increase in risk of lethal PCa. However, gene expression had less discriminatory accuracy than clinical variables alone for predicting lethal events. Transcript levels for several genes in the panel were significantly overexpressed in lethal versus non-recurrent PCa. Prostate © 2015 Wiley Periodicals, Inc.
    The Prostate 05/2015; DOI:10.1002/pros.23016 · 3.57 Impact Factor
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    ABSTRACT: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer (PrCa) risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of PrCa. We genotyped 25 PrCa susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical Odds Ratios for PrCa associated with different risk strata defined by PRS and derived age-specific absolute risks of developing PrCa by PRS stratum and family history. The PrCa risk for men in the top 1% of the PRS distribution was 30.6 (95% CI 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI 3.2-5.5) fold compared with the median risk. The absolute risk of PrCa by age 85 was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation=0.09). Risk profiling can identify men at substantially increased or reduced risk of PrCa. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of PrCa. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. Copyright © 2015, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 04/2015; 24(7). DOI:10.1158/1055-9965.EPI-14-0317 · 4.32 Impact Factor
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    ABSTRACT: Targeted cancer therapies offer great clinical promise, but treatment resistance is common, and basic research aimed at overcoming this challenge is limited by reduced genomic and biological complexity in artificially induced rodent tumors compared to their human counterparts. Animal models that more faithfully recapitulate genotype-specific human pathology could improve the predictive value of these investigations. Here, a newly identified animal model for oncogenic BRAF-driven cancers is described. With 20,000 new cases in the United States each year, canine invasive transitional cell carcinoma of the bladder (InvTCC) is a common, naturally occurring malignancy that shares significant histological, biological, and clinical phenotypes with human muscle invasive bladder cancer. In order to identify somatic drivers of canine InvTCC, the complete transcriptome for multiple tumors was determined by RNAseq. All tumors harbored a somatic mutation that is homologous to the human BRAF(V600E) mutation, and an identical mutation was present in 87% of 62 additional canine InvTCC tumors. The mutation was also detectable in the urine sediments of all dogs tested with mutationpositive tumors. Functional experiments suggest that, like human tumors, canine activating BRAF mutations potently stimulate the mitogen activated protein kinase (MAPK) pathway. Cell lines with the mutation have elevated levels of phosphorylated MEK, compared to a line with wild type BRAF. This effect can be diminished through application of the BRAF(V600E) inhibitor vemurafenib. These findings set the stage for canine InvTCC as a powerful system to evaluate BRAF-targeted therapies, as well as therapies designed to overcome resistance, which could enhance treatment of both human and canine cancers. This study demonstrates the activating BRAF mutation (V600E), which is found in multiple human cancers, is a driver of canine InvTCC, and highlights a urine-based test for quick diagnosis. Copyright © 2015, American Association for Cancer Research.
    Molecular Cancer Research 03/2015; 13(6). DOI:10.1158/1541-7786.MCR-14-0689 · 4.50 Impact Factor
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    ABSTRACT: Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤6, 7, ≥8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69-0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68-0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58-0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54-0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (<4.0 ng/mL) in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness.
    Human Genetics 02/2015; 134(4). DOI:10.1007/s00439-015-1534-9 · 4.52 Impact Factor
  • Deborah W Knapp · Deepika Dhawan · Elaine Ostrander
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    ABSTRACT: Cancer causes substantial morbidity and takes the lives of over 8 million people worldwide each year. Advances in cancer prevention research are crucial, and animal models are key to this. There are many valuable experimentally induced cancer models, but these do not fully meet the needs for cancer prevention studies. Pet dogs with risks for naturally occurring cancer can fill important gaps in cancer prevention research. Using invasive urothelial carcinoma (iUC) as an example, the advantages of utilizing pet dogs include: (1) close similarities between dogs and humans in carcinogenesis, molecular and cellular features, invasive and metastatic behavior, and response to treatment, thus providing high relevance for comparative studies, (2) shared environment between dogs and humans to help identify not-yet-known environmental iUC risks, (3) strong breed-associated risk (5- to 21-fold increased risk compared with mixed breeds) that facilitates investigation of gene-environment interactions, screening, and early intervention, (4) large size of dogs (versus rodents) that allows collection of fluids and tissues via cystoscopy, and detailed imaging at multiple time points, and (5) acceptance for studies in which each participating dog can benefit while enjoying life in their family environment, and in which findings will help other dogs and humans. An ongoing 3-year study in Scottish Terriers (comparable to a 15- to 20-year study in humans) is aimed at defining genetic and environmental risk factors for iUC, effective methods for screening/early detection, and a successful secondary cancer prevention approach with very promising results to date. Pet dogs can indeed propel cancer prevention research.
    01/2015; 35:e667-72. DOI:10.14694/EdBook_AM.2015.35.e667
  • Cancer Research 10/2014; 74(19 Supplement):1536-1536. DOI:10.1158/1538-7445.AM2014-1536 · 9.28 Impact Factor
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    ABSTRACT: Germline genetic variants have been suggested as prognostic biomarkers for identifying patients at high risk for lethal prostate cancer (PCa). Validation studies have confirmed the association of several single nucleotide polymorphisms (SNPs) with fatal PCa, but whether these variants affect PCa-specific mortality (PCSM) in patients with an inherited predisposition to PCa, based on familial history, is unknown. For this study, a cohort of 957 PCa patients from 270 hereditary prostate cancer (HPC) families of European ancestry was genotyped for a panel of 22 PCSM-associated SNPs. Death certificates were reviewed to confirm cause of death. Mixed-effect Cox proportional hazards models were used to assess survival according to genotypes, accounting for relatedness and clinicopathological factors. Within this cohort, 98 PCa deaths were confirmed over an average follow-up period of 12.7 years after diagnosis. Variant allele carriers for three SNPs had significantly altered risk for PCSM (rs635261 at RNASEL, HR, 0.35, 95% CI, 0.18-0.66; P = 0.002; rs915927 in XRCC1, HR, 1.91, 95% CI, 1.21−3.02; P = 0.009; and rs2494750 at AKT1, HR, 0.45, 95% CI, 0.23−0.90; P = 0.016). These results confirm the association of genetic variation in three genes with PCa lethality in a cohort of men with an inherited susceptibility to the disease and provide validation evidence that germline SNPs provide prognostic information for PCa patients. Development of a panel of germline biomarkers with clinical utility for distinguishing patients at detection who have an increased risk for fatal PCa is warranted. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 10/2014; 136(9). DOI:10.1002/ijc.29241 · 5.01 Impact Factor
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    Brennan Decker · Elaine A Ostrander
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    ABSTRACT: Prostate cancer (PC) is the most common noncutaneous cancer in men, and epidemiological studies suggest that about 40% of PC risk is heritable. Linkage analyses in hereditary PC families have identified multiple putative loci. However, until recently, identification of specific risk alleles has proven elusive. Cooney et al used linkage mapping and segregation analysis to identify a putative risk locus on chromosome 17q21-22. In search of causative variant(s) in genes from the candidate region, a novel, potentially deleterious G84E substitution in homeobox transcription factor gene HOXB13 was observed in multiple hereditary PC families. In follow-up testing, the G84E allele was enriched in cases, especially those with an early diagnosis or positive family history of disease. This finding was replicated by others, confirming HOXB13 as a PC risk gene. The HOXB13 protein plays diverse biological roles in embryonic development and terminally differentiated tissue. In tumor cell lines, HOXB13 participates in a number of biological functions, including coactivation and localization of the androgen receptor and FOXA1. However, no consensus role has emerged and many questions remain. All HOXB13 variants with a proposed role in PC risk are predicted to damage the protein and lie in domains that are highly conserved across species. The G84E variant has the strongest epidemiological support and lies in a highly conserved MEIS protein-binding domain, which binds cofactors required for activation. On the basis of epidemiological and biological data, the G84E variant likely modulates the interaction between the HOXB13 protein and the androgen receptor, as well as affecting FOXA1-mediated transcriptional programming. However, further studies of the mutated protein are required to clarify the mechanisms by which this translates into PC risk.
    Pharmacogenomics and Personalized Medicine 08/2014; 7:193-201. DOI:10.2147/PGPM.S38117
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    ABSTRACT: Fanconi anemia (FA) is a rare recessive disease resulting from mutations in one of at least 16 different genes. Mutation types and phenotypic manifestations of FA are highly heterogeneous and influence the clinical management of the disease. We analyzed 202 FA families for large deletions, using high-resolution Comparative Genome Hybridization arrays (arrayCGH), Single Nucleotide Polymorphism arrays (SNParrays) and DNA sequencing. We found pathogenic deletions in 88 FANCA, seven FANCC, two FANCD2, and one FANCB families. We find 35% of FA families carry large deletions, accounting for 18% of all FA pathogenic variants. Cloning and sequencing across the deletion breakpoints revealed that 52 FANCA deletion ends, and one FANCC deletion end extended beyond the gene boundaries, potentially affecting neighboring genes with phenotypic consequences. Seventy-five percent of the FANCA deletions are Alu-Alu mediated, predominantly by AluY elements, and appear to be caused by Non-Allelic Homologous Recombination. Individual Alu hotspots were identified. Defining the haplotypes of four FANCA deletions shared by multiple families revealed that three share a common ancestry. Knowing the exact molecular changes that lead to the disease may be critical for a better understanding of the FA phenotype, and to gain insight into the mechanisms driving these pathogenic deletion variants.This article is protected by copyright. All rights reserved
    Human Mutation 08/2014; 35(11). DOI:10.1002/humu.22680 · 5.05 Impact Factor
  • Jeffrey J Schoenebeck · Elaine A Ostrander
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    ABSTRACT: Although most modern dog breeds are less than 200 years old, the symbiosis between man and dog is ancient. Since prehistoric times, repeated selection events have transformed the wolf into man's guardians, laborers, athletes, and companions. The rapid transformation from pack predator to loyal companion is a feat that is arguably unique among domesticated animals. How this transformation came to pass remained a biological mystery until recently: Within the past decade, the deployment of genomic approaches to study population structure, detect signatures of selection, and identify genetic variants that underlie canine phenotypes is ushering into focus novel biological mechanisms that make dogs remarkable. Ironically, the very practices responsible for breed formation also spurned morbidity; today, many diseases are correlated with breed identity. In this review, we discuss man's best friend in the context of a genetic model to understand paradigms of heritable phenotypes, both desirable and disadvantageous. Expected final online publication date for the Annual Review of Cell and Developmental Biology Volume 30 is October 06, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
    Annual Review of Cell and Developmental Biology 07/2014; 30(1). DOI:10.1146/annurev-cellbio-100913-012927 · 20.24 Impact Factor
  • Brian W Davis · Elaine A Ostrander
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    ABSTRACT: Domestic dogs are unique from other animal models of cancer in that they generally experience spontaneous disease. In addition, most types of cancer observed in humans are found in dogs, suggesting that canines may be an informative system for the study of cancer genetics. Domestic dogs are divided into over 175 breeds, with members of each breed sharing significant phenotypes. The breed barrier enhances the utility of the model, especially for genetic studies where small numbers of genes are hypothesized to account for the breed cancer susceptibility. These facts, combined with recent advances in high-throughput sequencing technologies allows for an unrivaled ability to use pet dog populations to find often subtle mutations that promote cancer susceptibility and progression in dogs as a whole. The meticulous record keeping associated with dog breeding makes the model still more powerful, as it facilitates both association analysis and family-based linkage studies. Key to the success of these studies is their cooperative nature, with owners, scientists, veterinarians and breed clubs working together to avoid the cost and unpopularity of developing captive populations. In this article we explore these principals and advocate for colony-free, genetic studies that will enhance our ability to diagnose and treat cancer in dogs and humans alike.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 06/2014; 55(1):59-68. DOI:10.1093/ilar/ilu017 · 1.05 Impact Factor
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    ABSTRACT: Background. One challenge in prostate cancer (PCa) is distinguishing indolent from aggressive disease at diagnosis. DNA promoter hypermethylation is a frequent epigenetic event in PCa, but few studies of DNA methylation in relation to features of more aggressive tumors or PCa recurrence have been completed. Methods. We used the Infinium® HumanMethylation450 BeadChip to assess DNA methylation in tumor tissue from 407 patients with clinically localized PCa who underwent radical prostatectomy. Recurrence status was determined by follow-up surveys, medical record review, and linkage with the SEER registry. The methylation status of 14 genes for which promoter hypermethylation was previously correlated with advanced disease or biochemical recurrence was evaluated. Average methylation level for promoter region CpGs in patients who recurred compared to those with no evidence of recurrence was analyzed. For two genes with differential methylation, time to recurrence was examined. Results. During an average follow-up of 11.7 years, 104 (26%) patients recurred. Significant promoter hypermethylation in at least 50% of CpG sites in two genes, ABHD9 and HOXD3, was found in tumors from patients who recurred compared to those without recurrence. Evidence was strongest for HOXD3 (lowest P = 9.46x10-6), with higher average methylation across promoter region CpGs associated with reduced recurrence-free survival (P = 2x10-4). DNA methylation profiles did not differ by recurrence status for the other genes. Conclusions. These results validate the association between promoter hypermethylation of ADHB9 and HOXD3 and PCa recurrence. Impact. Tumor DNA methylation profiling may help distinguish PCa patients at higher risk for disease recurrence.
    Cancer Epidemiology Biomarkers & Prevention 04/2014; 23. DOI:10.1158/1055-9965.EPI-13-1000 · 4.32 Impact Factor
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    ABSTRACT: Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case–control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p ≤ 1E −3) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.
    Human Genetics 03/2014; 133(3):347-356. DOI:10.1007/s00439-013-1384-2 · 4.52 Impact Factor
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    ABSTRACT: Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial p
  • H. G. Parker · E. A. Ostrander
    Science 02/2014; 343(6172):730-730. · 31.48 Impact Factor
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    ABSTRACT: The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.
    PLoS Genetics 02/2014; 10(2):e1004129. DOI:10.1371/journal.pgen.1004129 · 8.17 Impact Factor
  • Heidi G Parker · Elaine A Ostrander
    Science 01/2014; 343(6169):376-8. DOI:10.1126/science.1248812 · 31.48 Impact Factor

Publication Stats

15k Citations
2,789.07 Total Impact Points

Institutions

  • 2015
    • NorthShore University HealthSystem
      • Division of Urology
      Chicago, Illinois, United States
  • 2005–2015
    • National Human Genome Research Institute
      베서스다, Maryland, United States
    • Measured Progress
      Довер, New Hampshire, United States
  • 2006–2014
    • National Institutes of Health
      • Branch of Cancer Genetics
      베서스다, Maryland, United States
    • Princeton University
      • Department of Ecology and Evolutionary Biology
      Princeton, New Jersey, United States
  • 2009–2013
    • Institute of Cancer Research
      Londinium, England, United Kingdom
    • Boston Scientific
      Boston, Massachusetts, United States
  • 1993–2013
    • Fred Hutchinson Cancer Research Center
      • • Division of Public Health Sciences
      • • Division of Human Biology
      • • Division of Clinical Research
      • • Transplantation Biology Program
      Seattle, Washington, United States
  • 2011
    • Clemson University
      • Department of Genetics and Biochemistry
      Anderson, Indiana, United States
  • 1997–2009
    • University of Utah
      • Department of Biology
      Salt Lake City, Utah, United States
    • Seattle Institute for Biomedical and Clinical Research
      Seattle, Washington, United States
  • 1999–2008
    • University of Washington Seattle
      • • Division of Gerontology and Geriatric Medicine
      • • Division of Medical Genetics
      Seattle, Washington, United States
  • 2007
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 2004–2006
    • University of California, Los Angeles
      • Department of Ecology and Evolutionary Biology
      Los Angeles, CA, United States
  • 1999–2003
    • Cornell University
      • College of Veterinary Medicine
      Ithaca, NY, United States
  • 2002
    • Jules Stein Eye Institute
      Maryland, United States
  • 1993–1994
    • University of California, Berkeley
      • Department of Molecular and Cell Biology
      Berkeley, California, United States