Author
Ruth C. Travis
Other affiliations: Clinical Trial Service Unit, University of Oxford, Cancer Research UK ...read more
Bio: Ruth C. Travis is an academic researcher from Cancer Epidemiology Unit. The author has contributed to research in topics: Prostate cancer & Cancer. The author has an hindex of 63, co-authored 237 publications receiving 15741 citations. Previous affiliations of Ruth C. Travis include Clinical Trial Service Unit & University of Oxford.
Papers published on a yearly basis
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Bjarni J. Vilhjálmsson1, Jian Yang2, Hilary K. Finucane3, Alexander Gusev4 +391 more•Institutions (14)
TL;DR: LDpred is introduced, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel, and outperforms the approach of pruning followed by thresholding, particularly at large sample sizes.
Abstract: Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R(2) increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase.
1,088 citations
University of Cambridge1, Australian National University2, Norwegian Institute of Public Health3, Utrecht University4, University of Tromsø5, The George Institute for Global Health6, Johns Hopkins University7, University of Oxford8, National Institutes of Health9, Copenhagen University Hospital10, University of Copenhagen11, Fiona Stanley Hospital12, University of Western Australia13, Harry Perkins Institute of Medical Research14, University of London15, Lund University16, University of Pittsburgh17, French Institute of Health and Medical Research18, University College London19, University of Ulm20, Technische Universität München21, University of Padua22, University of Southampton23, German Cancer Research Center24, Erasmus University Medical Center25, Umeå University26, Cardiff University27, Greifswald University Hospital28, Aarhus University29, Portland State University30, University of New South Wales31, Harvard University32, National and Kapodistrian University of Athens33, University of Hawaii34, Columbia University35, University of Iowa36, Duke University37, Yamagata University38, Tuskegee University39, University of Helsinki40, University of Oulu41, Medical University of South Carolina42, Kaiser Permanente43, University of Washington44, University of Groningen45, University of Granada46, Yale University47, Prevention Institute48, University of Edinburgh49, Uppsala University50, Basque Government51, Kyushu University52, Royal Prince Alfred Hospital53, Harokopio University54, University of California, San Diego55, VU University Medical Center56, Aalborg University57, University of Eastern Finland58, Laval University59, University of Vermont60, Wake Forest University61, Wake Forest Baptist Medical Center62, Kanazawa Medical University63, Baker IDI Heart and Diabetes Institute64, Heidelberg University65, Istituto Superiore di Sanità66, Pasteur Institute67, City College of New York68, Howard University69, University of Glasgow70, International Agency for Research on Cancer71, University of Bristol72, University of Auckland73
TL;DR: Current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week, and data support limits for alcohol consumption that are lower than those recommended in most current guidelines.
711 citations
TL;DR: Overweight/obesity increases the risk for cancers of the oesophagus, colorectum, breast, breast (postmenopausal), endometrium and kidney, and diets should include at least 400?g/d of total fruits and vegetables.
Abstract: Objective: To assess the epidemiological evidence on diet and cancer and make public health recommendations. Design: Review of published studies, concentrating on recent systematic reviews, meta-analyses and large prospective studies. Conclusions and recommendations: Overweight/obesity increases the risk for cancers of the oesophagus (adenocarcinoma), colorectum, breast (postmenopausal), endometrium and kidney; body weight should be maintained in the body mass index range of 18.5-25 kg/m 2 , and weight gain in adulthood avoided. Alcohol causes cancers of the oral cavity, pharynx, oesophagus and liver, and a small increase in the risk for breast cancer; if consumed, alcohol intake should not exceed 2 units/d. Aflatoxin in foods causes liver cancer, although its importance in the absence of hepatitis virus infections is not clear; exposure to aflatoxin in foods should be minimised. Chinese-style salted fish increases the risk for nasopharyngeal cancer, particularly if eaten during childhood, and should be eaten only in moderation. Fruits and vegetables probably reduce the risk for cancers of the oral cavity, oesophagus, stomach and colorectum, and diets should include at least 400 g/d of total fruits and vegetables. Preserved meat and red meat probably increase the risk for colorectal cancer; if eaten, consumption of these foods should be moderate. Salt preserved foods and high salt intake probably increase the risk for stomach cancer; overall consumption of salt preserved foods and salt should be moderate. Very hot drinks and foods probably increase the risk for cancers of the oral cavity, pharynx and oesophagus; drinks and foods should not be consumed when they are scalding hot. Physical activity, the main determinant of energy expenditure, reduces the risk for colorectal cancer and probably reduces the risk for breast cancer; regular physical activity should be taken.
658 citations
Fredrick R. Schumacher1, Ali Amin Al Olama2, Sonja I. Berndt3, Sara Benlloch2 +204 more•Institutions (79)
TL;DR: A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology of PrCa1.
Abstract: Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10−9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55–2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04–6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1. A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.
585 citations
Princess Margaret Cancer Centre1, Wellcome Trust Sanger Institute2, University of Cambridge3, University of Toronto4, Weizmann Institute of Science5, Ontario Institute for Cancer Research6, International Agency for Research on Cancer7, European Bioinformatics Institute8, University Health Network9, Norwich University10, University of East Anglia11, National and Kapodistrian University of Athens12, University of Milan13, University of Granada14, Cancer Epidemiology Unit15, Prevention Institute16, University of Naples Federico II17, German Cancer Research Center18, Imperial College London19, Utrecht University20, Memorial Sloan Kettering Cancer Center21
TL;DR: Deep sequencing is used to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH, providing proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation.
Abstract: The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure1. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion2,3. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)4–8. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.
567 citations
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29 Sep 2017
TL;DR: Thank you very much for reading who classification of tumours of haematopoietic and lymphoid tissues, and maybe you have knowledge that, people have look hundreds of times for their chosen readings like this, but end up in malicious downloads.
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TL;DR: The following Clinical Practice Guidelines will give up-to-date advice for the clinical management of patients with hepatocellular carcinoma, as well as providing an in-depth review of all the relevant data leading to the conclusions herein.
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TL;DR: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors.
Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many
6,968 citations
Massachusetts Institute of Technology1, Broad Institute2, University of California, Los Angeles3, University of British Columbia4, Baylor College of Medicine5, Howard Hughes Medical Institute6, University of Washington7, Ludwig Institute for Cancer Research8, University of California, San Francisco9, University of Connecticut10, University of Zagreb11, University of Texas at Austin12, Washington University in St. Louis13, University of Queensland14, Harvard University15, Cold Spring Harbor Laboratory16, University of Southern California17, University of California, Santa Cruz18, Simon Fraser University19, Morgridge Institute for Research20, University of Texas at Dallas21, National Institutes of Health22
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
5,037 citations