Showing papers by "International Agency for Research on Cancer published in 2020"
TL;DR: The global scale-up of HPV vaccination and HPV-based screening—including self-sampling—has potential to make cervical cancer a rare disease in the decades to come, and could help shape and monitor the initiative to eliminate cervical cancer as a major public health problem.
1,867 citations
TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.
1,600 citations
TL;DR: For the first time, certain tumour types are defined as much by their molecular phenotype as their histological characteristics; however, histopathological classification remains the gold standard for diagnosis in most instances.
Abstract: The WHO classification of digestive system tumours presented in the first volume of the WHO classification of tumours series, 5th edition, reflects important advancements in our understanding of tumours of the digestive system (Table (Table1).1). For the first time, certain tumour types are defined as much by their molecular phenotype as their histological characteristics; however, in most instances histopathological classification remains the gold standard for diagnosis. The WHO classification of tumours series is designed to be used worldwide, including those settings where a lack of tissue samples or of specific technical facilities limits the pathologist's ability to rely on molecular testing.
Table 1
Selected changes within the new classification of tumours of the digestive system
1,583 citations
TL;DR: The cancer burden attributed to human papillomavirus showed the clearest relationship with country income level, and infection-attributable cancer incidence allows for refined geographic analyses and identification of populations with a high infection-associated cancer burden.
877 citations
TL;DR: There was a uniform decrease in gastric cancer incidence but an increasing incidence of colorectal cancer in formerly low-incidence regions over the studied time period, and slight increases in incidence of liver and pancreatic cancer in some high-income regions.
670 citations
TL;DR: Recent trends in prostate cancer incidence and mortality rates have been on the decline or have stabilized recently in many countries, with decreases more pronounced in high-income countries.
547 citations
University of California, Davis1, University of California, Berkeley2, California Pacific Medical Center3, Organisation for Economic Co-operation and Development4, North Carolina State University5, International Agency for Research on Cancer6, Brunel University London7, United States Environmental Protection Agency8, University of California, San Francisco9, Maastricht University10, National Institute for Environmental Studies11, National Institutes of Health12, University of Texas at Austin13, California Environmental Protection Agency14
TL;DR: This Expert Consensus Statement reflects on how these ten KCs can be used to identify, organize and utilize mechanistic data when evaluating chemicals as EDCs, and uses diethylstilbestrol, bisphenol A and perchlorate as examples to illustrate this approach.
Abstract: Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with hormone action, thereby increasing the risk of adverse health outcomes, including cancer, reproductive impairment, cognitive deficits and obesity. A complex literature of mechanistic studies provides evidence on the hazards of EDC exposure, yet there is no widely accepted systematic method to integrate these data to help identify EDC hazards. Inspired by work to improve hazard identification of carcinogens using key characteristics (KCs), we have developed ten KCs of EDCs based on our knowledge of hormone actions and EDC effects. In this Expert Consensus Statement, we describe the logic by which these KCs are identified and the assays that could be used to assess several of these KCs. We reflect on how these ten KCs can be used to identify, organize and utilize mechanistic data when evaluating chemicals as EDCs, and we use diethylstilbestrol, bisphenol A and perchlorate as examples to illustrate this approach.
390 citations
Singapore General Hospital1, University of Nottingham2, Stanford University3, Memorial Sloan Kettering Cancer Center4, Peter MacCallum Cancer Centre5, Royal Brisbane and Women's Hospital6, University of Texas at Austin7, University of Turin8, Tohoku University9, Brigham and Women's Hospital10, Université libre de Bruxelles11, University Medical Center Utrecht12, International Agency for Research on Cancer13
TL;DR: The newly published World Health Organization (WHO) Classification of Tumours of the breast features significant changes compared to earlier editions, and this review outlines the major changes.
Abstract: The newly published World Health Organization (WHO) Classification of Tumours of the breast features significant changes compared to earlier editions. In this review, we outline the major changes in this important reference source for those diagnosing tumours, or engaged in cancer research, and describe the significant changes. For breast cancer, the overview acknowledges the treatment-relevant subtypes of invasive carcinoma (based on ER and HER2 status) and new data is added to support the differences in pathogenesis, treatment response and prognosis of these clinically relevant groupings. The WHO Classification of Tumours is increasingly evidence-based, with a clear update cycle, improved quality of illustrations, as well as content, led by an editorial board comprising pathologists, but increasingly incorporating input from other disciplines. The advent of the new website allows the use of whole slide images, and hyperlinks to evidence or external bodies that produce guidance on staging or reporting.
375 citations
Imperial College London1, Laval University2, Harvard University3, Cancer Council New South Wales4, University of New South Wales5, University of Sydney6, University of Oslo7, University of Hong Kong8, Public Health England9, University of London10, International Agency for Research on Cancer11, World Health Organization12
TL;DR: It is suggested that high HPV vaccination coverage of girls can lead to cervical cancer elimination in most LMICs by the end of the century, and elimination could occur between 2059 and 2102, depending on the threshold and region.
358 citations
Harvard University1, University of Amsterdam2, National Institutes of Health3, Northwestern University4, German Cancer Research Center5, Humboldt University of Berlin6, International Agency for Research on Cancer7, Johns Hopkins University8, Aix-Marseille University9, University of Cincinnati10, University of Texas MD Anderson Cancer Center11, University of Bologna12, Mayo Clinic13, Medical University of Vienna14, University of Toronto15, Erasmus University Rotterdam16, The Chinese University of Hong Kong17, Seoul National University18, University of Münster19, University of California, San Francisco20, University of Bonn21, University of Düsseldorf22, Memorial Sloan Kettering Cancer Center23, Cambridge University Hospitals NHS Foundation Trust24, Heidelberg University25, All India Institute of Medical Sciences26, University of Zurich27
TL;DR: Working Committee 3 recommended that a substantial number of newly recognized types and subtypes should be considered for inclusion in future CNS tumor classifications.
Abstract: cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to evaluate and make practical recommendations on recent advances in the field of CNS tumor classification, particularly in light of the rapid progress in molecular insights into these neoplasms. For Round 2 of its deliberations, cIMPACT-NOW Working Committee 3 was reconstituted and convened in Utrecht, The Netherlands, for a meeting designed to review putative new CNS tumor types in advance of any future World Health Organization meeting on CNS tumor classification. In preparatory activities for the meeting and at the actual meeting, a list of possible entities was assembled and each type and subtype debated. Working Committee 3 recommended that a substantial number of newly recognized types and subtypes should be considered for inclusion in future CNS tumor classifications. In addition, the group endorsed a number of principles-relating to classification categories, approaches to classification, nomenclature, and grading-that the group hopes will also inform the future classification of CNS neoplasms.
330 citations
TL;DR: Evidence of a rising burden of both premenopausal and postmenopausal breast cancer worldwide is provided, although early diagnosis and access to treatment remain crucial in low-income and middle-income countries.
National Institute for Health Research1, Harvard University2, Montreal Heart Institute3, University of North Carolina at Chapel Hill4, Wellcome Trust Sanger Institute5, VA Boston Healthcare System6, Osaka University7, Icahn School of Medicine at Mount Sinai8, University of Wisconsin–Milwaukee9, Kyushu University10, University of Washington11, University of Bristol12, University of Copenhagen13, Erasmus University Medical Center14, National Institutes of Health15, Veterans Health Administration16, Kaiser Permanente17, International Agency for Research on Cancer18, Wake Forest University19, Imperial College London20, Broad Institute21, Greifswald University Hospital22, University of Pennsylvania23, British Heart Foundation24, Fred Hutchinson Cancer Research Center25, Chinese National Human Genome Center26, Technische Universität München27, University of Tampere28, University of Tokyo29, University of Ioannina30, University of Colorado Denver31, Duke University32, University of Virginia33, University of Minnesota34, Turku University Hospital35, Los Angeles Biomedical Research Institute36, Stanford University37, Mashhad University of Medical Sciences38, NHS Blood and Transplant39, Brigham and Women's Hospital40, University of Oxford41, University of Liège42, European Bioinformatics Institute43, John Radcliffe Hospital44
TL;DR: The results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
TL;DR: The impact of achieving the 90–70–90 triple-intervention targets on cervical cancer mortality and deaths averted over the next century is assessed and the potential for the elimination initiative to support target 3.4 of the UN Sustainable Development Goals is assessed.
TL;DR: An estimated 12 million people worldwide have experienced HDV infection, with higher prevalence in certain geographic areas and populations, and was higher in injecting drug users, haemodialysis recipients, men who have sex with men, commercial sex workers, and those with HCV or HIV.
TL;DR: Gains in the control of liver cancer are at risk of being reversed by the growing obesity and diabetes epidemics, suggesting diabetes treatment and primary prevention of obesity will be key in reducing liver cancer in the longer‐term.
Abstract: Primary liver cancer, the major histology of which is hepatocellular carcinoma (HCC), is the second leading cause of cancer death worldwide. We comprehensively examined recent international trends of primary liver cancer and HCC incidence using population-based cancer registry data. Incidence for all primary liver cancer and for HCC by calendar time and birth cohort was examined for selected countries between 1978 and 2012. For each successive 5-year period, age-standardized incidence rates were calculated from Volumes V to XI of the Cancer Incidence in Five Continents (CI5) series using the online electronic databases, CI5plus. Large variations persist in liver cancer incidence globally. Rates of liver cancer remain highest in Asian countries, specifically in the East and South-East, and Italy. However, rates in these high-risk countries have been decreasing in recent years. Rates in India and in most countries of Europe, the Americas and Oceania are rising. As the population seroprevalence of hepatitis B virus (HBV) continues to decline, we anticipate rates of HCC in many high-risk countries will continue to decrease. Treatment of hepatitis C virus (HCV) is likely to bring down rates further in some high-rate, as well as low-rate, countries with access to effective therapies. However, such gains in the control of liver cancer are at risk of being reversed by the growing obesity and diabetes epidemics, suggesting diabetes treatment and primary prevention of obesity will be key in reducing liver cancer in the longer-term.
TL;DR: These updated estimates of the global burden of oesophageal and gastric cancer by subtype and site suggest an ongoing transition in epidemiological patterns and will aid in developing appropriate cancer control strategies.
Abstract: Objectives To provide updated estimates of the global burden of oesophageal and gastric cancer by subsite and type Methods Using data from population-based cancer registries, proportions of oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC) out of all oesophageal as well as cardia gastric cancer (CGC) and non-CGC (NCGC) out of all gastric cancer cases were computed by country, sex and age group Proportions were subsequently applied to the estimated numbers of oesophageal and gastric cancer cases from GLOBOCAN 2018 Age-standardised incidence rates (ASR) were calculated Results In 2018, there were an estimated 572 000 new cases of oesophageal cancer worldwide, 85 000 OACs (ASR 09 per 100 000, both sexes combined) and 482 000 OSCCs (ASR 53) Out of 103 million gastric cancers, there were an estimated 181 000 cases of CGC (ASR 20) and 853 000 cases of NCGC (ASR 92) While the highest incidence rates of OSCC, CGC and NCGC were observed in Eastern Asia (ASRs 111, 44 and 179, respectively), rates of OAC were highest in Northern Europe (ASR 35) While globally OSCC and NCGC remain the most common types of oesophageal and gastric cancer, respectively, rates of OAC exceed those of OSCC in an increasing number of high-income countries Conclusions These updated estimates of the global burden of oesophageal and gastric cancer by subtype and site suggest an ongoing transition in epidemiological patterns This work will serve as a cornerstone for policy-making and will aid in developing appropriate cancer control strategies
University of São Paulo1, University of Antioquia2, Fox Chase Cancer Center3, Pamela Youde Nethersole Eastern Hospital4, Utrecht University5, University of Udine6, Radboud University Nijmegen7, University of Helsinki8, Karolinska Institutet9, International Agency for Research on Cancer10, University of Michigan11, The Royal Marsden NHS Foundation Trust12, Institut Gustave Roussy13, Katholieke Universiteit Leuven14, University of Edinburgh15, University of Milan16, Beaumont Hospital17, University of Oviedo18, University of Florida19, Tata Memorial Hospital20, University of Hong Kong21
TL;DR: The 2019 novel coronavirus disease (COVID‐19) is a highly contagious zoonosis produced by SARS‐CoV‐2 that is spread human‐to‐human by respiratory secretions that was declared by the WHO as a public health emergency.
Abstract: The 2019 novel coronavirus disease (COVID-19) is a highly contagious zoonosis produced by SARS-CoV-2 that is spread human-to-human by respiratory secretions. It was declared by the WHO as a public health emergency. The most susceptible populations, needing mechanical ventilation, are the elderly and people with associated comorbidities. There is an important risk of contagion for anesthetists, dentists, head and neck surgeons, maxillofacial surgeons, ophthalmologists, and otolaryngologists. Health workers represent between 3.8% and 20% of the infected population; some 15% will develop severe complaints and among them, many will lose their lives. A large number of patients do not have overt signs and symptoms (fever/respiratory), yet pose a real risk to surgeons (who should know this fact and must therefore apply respiratory protective strategies for all patients they encounter). All interventions that have the potential to aerosolize aerodigestive secretions should be avoided or used only when mandatory. Health workers who are: pregnant, over 55 to 65 years of age, with a history of chronic diseases (uncontrolled hypertension, diabetes mellitus, chronic obstructive pulmonary diseases, and all clinical scenarios where immunosuppression is feasible, including that induced to treat chronic inflammatory conditions and organ transplants) should avoid the clinical attention of a potentially infected patient. Health care facilities should prioritize urgent and emergency visits and procedures until the present condition stabilizes; truly elective care should cease and discussed on a case-by-case basis for patients with cancer. For those who are working with COVID-19 infected patients' isolation is compulsory in the following settings: (a) unprotected close contact with COVID-19 pneumonia patients; (b) onset of fever, cough, shortness of breath, and other symptoms (gastrointestinal complaints, anosmia, and dysgeusia have been reported in a minority of cases). For any care or intervention in the upper aerodigestive tract region, irrespective of the setting and a confirmed diagnosis (eg, rhinoscopy or flexible laryngoscopy in the outpatient setting and tracheostomy or rigid endoscopy under anesthesia), it is strongly recommended that all health care personnel wear personal protective equipment such as N95, gown, cap, eye protection, and gloves. The procedures described are essential in trying to maintain safety of health care workers during COVID-19 pandemic. In particular, otolaryngologists, head and neck, and maxillofacial surgeons are per se exposed to the greatest risk of infection while caring for COVID-19 positive subjects, and their protection should be considered a priority in the present circumstances.
University of North Carolina at Chapel Hill1, Montreal Heart Institute2, Osaka University3, VA Boston Healthcare System4, Icahn School of Medicine at Mount Sinai5, Queen Mary University of London6, University of Cambridge7, National Institute for Health Research8, Wellcome Trust Sanger Institute9, Harvard University10, Vanderbilt University11, University of Wisconsin–Milwaukee12, Université de Montréal13, University of Southern California14, Kyushu University15, University of Washington16, University of Bristol17, University of Copenhagen18, Erasmus University Medical Center19, National Institutes of Health20, Brigham and Women's Hospital21, Kaiser Permanente22, University of Mississippi Medical Center23, International Agency for Research on Cancer24, Wake Forest University25, Imperial College London26, Broad Institute27, University of Pennsylvania28, Greifswald University Hospital29, Fred Hutchinson Cancer Research Center30, Chinese National Human Genome Center31, Technische Universität München32, University of Tampere33, University of Tokyo34, University of Ioannina35, University of Colorado Denver36, Duke University37, University of Virginia38, NHS Blood and Transplant39, University of Minnesota40, Turku University Hospital41, Los Angeles Biomedical Research Institute42, Stanford University43, King's College London44, Mashhad University of Medical Sciences45, Veterans Health Administration46
TL;DR: The clinical significance and predictive value of trans-ethnic variants in multiple populations are explored, genetic architecture and the effect of natural selection on these blood phenotypes between populations are compared and the value of a more global representation of populations in genetic studies is highlighted.
New York University1, University of Malaya2, University of Pennsylvania3, Susan G. Komen for the Cure4, Queen's University5, International Agency for Research on Cancer6, University of Panama7, National Autonomous University of Mexico8, Pontifical Xavierian University9, Brigham and Women's Hospital10, Ohio State University11, Mount Sinai Hospital12, Icahn School of Medicine at Mount Sinai13, Johns Hopkins University14, University of Washington15, World Bank Group16, Eastern Michigan University17
TL;DR: In this paper, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis, and highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real world settings are considered.
Abstract: When breast cancer is detected and treated early, the chances of survival are very high. However, women in many settings face complex barriers to early detection, including social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast health care services. Previously, the Breast Health Global Initiative (BHGI) developed resource-stratified guidelines for the early detection and diagnosis of breast cancer. In this consensus article from the sixth BHGI Global Summit held in October 2018, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis. The core issues address include finance and governance, which pertain to successful planning, implementation, and the iterative process of program improvement and are needed for a breast cancer early detection program to succeed in any resource setting. Examples are presented of implementation, process, and clinical outcome metrics that assist in program implementation monitoring. Country case examples are presented to highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real-world settings are considered.
TL;DR: This Review is a comprehensive and updated review on the development of population-based cancer registries in China over a 60-year time span and highlights some aspects of cancer control plans that illustrate how cancer registration data have become central to the identification of health priorities for China.
Abstract: Cancer has become a leading cause of death in China, with an increasing burden of cancer incidence and mortality observed over the past half century. Population-based cancer registries have been operating in China for about 60 years, and, in 2018, their role has expanded to include the formulation and evaluation of national cancer control programmes and the care of patients with cancer. The purpose of this Review is to provide an overview of the key milestones in the development of cancer registration in China, the current status of registry coverage and quality, and a description of the changing cancer profile in China from 1973 to 2015. This Review is a comprehensive and updated review on the development of population-based cancer registries in China over a 60-year time span. We highlight some aspects of cancer control plans that illustrate how cancer registration data have become central to the identification of health priorities for China and provide a means to track progress in cancer control for the country.
19 May 2020
TL;DR: Tests using the S antigen are more sensitive than N antigen-based tests and ELISA tests could be a safer choice at this stage of the pandemic, and LFIA tests are more attractive for large seroprevalence studies but show lower sensitivity, and this should be taken into account when designing and performing serop revalences studies.
Abstract: The emergence of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 made imperative the need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies are usually inconclusive, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis in PubMed, medRxiv and bioRxiv. We used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA), and the Lateral Flow Immunoassays (LFIA). We identified 38 studies containing data from 7848 individuals. Tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody alone. All methods yield high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods perform better in terms of sensitivity (90%-94%) followed by LFIA and FIA with sensitivities ranging from 80% to 89%. ELISA tests could be a safer choice at this stage of the pandemic. LFIA tests are more attractive for large seroprevalence studies but show lower sensitivity, and this should be taken into account when designing and performing seroprevalence studies.
TL;DR: The general term melanocytoma is proposed to encompass "intermediate" tumors that have an increased (though still low) probability of disease progression to melanoma, which is based on the 4th edition of the WHO Classification of Skin Tumours, published in 2018.
Abstract: Context.— There have been major advances in the understanding of melanoma since the last revision of the World Health Organization (WHO) classification in 2006. Objective.— To discuss development o...
TL;DR: Overall gastric cancer incidence rates are predicted to continue falling in the future in the majority of countries, including high-incidence countries such as Japan but also low- incidence countriessuch as Australia, and increasing risks have been observed in younger generations.
Abstract: Objectives The incidence of gastric cancer continues to decrease globally, approaching levels that in some populations could define it as a rare disease. To explore this on a wider scale, we predict its future burden in 34 countries with long-standing population-based data. Methods Data on gastric cancer incidence by year of diagnosis, sex and age were extracted for 92 cancer registries in 34 countries included in Cancer Incidence in Five Continents Plus. Numbers of new cases and age-standardised incidence rates (ASR per 100 000) were predicted up to 2035 by fitting and extrapolating age–period–cohort models. Results Overall gastric cancer incidence rates are predicted to continue falling in the future in the majority of countries, including high-incidence countries such as Japan (ASR 36 in 2010 vs ASR 30 in 2035) but also low-incidence countries such as Australia (ASR 5.1 in 2010 vs ASR 4.6 in 2035). A total of 16 countries are predicted to fall below the rare disease threshold (defined as 6 per 100 000 person-years) by 2035, while the number of newly diagnosed cases remains high and is predicted to continue growing. In contrast, incidence increases were seen in younger age groups (below age 50 years) in both low-incidence and high-incidence populations. Conclusions While gastric cancer is predicted to become a rare disease in a growing number of countries, incidence levels remain high in some regions, and increasing risks have been observed in younger generations. The predicted growing number of new cases highlights that gastric cancer remains a major challenge to public health on a global scale.
Wellcome Trust Sanger Institute1, National Institute for Health Research2, Boston Children's Hospital3, Broad Institute4, Montreal Heart Institute5, British Heart Foundation6, University of North Carolina at Chapel Hill7, VA Boston Healthcare System8, NHS Blood and Transplant9, University of Cambridge10, Osaka University11, Icahn School of Medicine at Mount Sinai12, University of Wisconsin–Milwaukee13, Kyushu University14, University of Washington15, University of Bristol16, University of Copenhagen17, Hasso Plattner Institute18, Erasmus University Medical Center19, National Institutes of Health20, Harvard University21, Brigham and Women's Hospital22, Kaiser Permanente23, University of Mississippi Medical Center24, International Agency for Research on Cancer25, University of Ioannina26, Wake Forest University27, Greifswald University Hospital28, University of Pennsylvania29, Fred Hutchinson Cancer Research Center30, Chinese National Human Genome Center31, Technische Universität München32, University of Tampere33, University of Tokyo34, University of Colorado Denver35, Frederiksberg Hospital36, Duke University37, University of Virginia38, University of Minnesota39, University of Turku40, Turku University Hospital41, Los Angeles Biomedical Research Institute42, Stanford University43, Université de Montréal44, Veterans Health Administration45, University of Oxford46, University of Liège47, European Bioinformatics Institute48, Imperial College London49, Churchill Hospital50, John Radcliffe Hospital51
TL;DR: These results show the power of large-scale blood cell GWAS to interrogate clinically meaningful variants across the full allelic spectrum of human variation.
Abstract: Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including 563,946 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering the full allele frequency spectrum of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood cell traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell GWAS to interrogate clinically meaningful variants across the full allelic spectrum of human variation.
University College London1, University of Cambridge2, University of California, San Francisco3, RMIT University4, Karolinska Institutet5, Queen Mary University of London6, University of Manchester7, Laval University8, Max Planck Society9, International Agency for Research on Cancer10, Institute of Cancer Research11, Institut Gustave Roussy12, Netherlands Cancer Institute13, University of Antwerp14, National Institute for Health Research15, Radboud University Nijmegen16, University of Tartu17, Erasmus University Rotterdam18, Leiden University19
TL;DR: This Consensus Statement discusses the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation and presents recommendations on priorities for future research in each of these areas with the aim of stimulating and guiding risk-adapted breast cancer prevention and screening programmes.
Abstract: The European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) brings together several international research consortia working on different aspects of the personalized early detection and prevention of breast cancer. In a consensus conference held in 2019, the members of this network identified research areas requiring development to enable evidence-based personalized interventions that might improve the benefits and reduce the harms of existing breast cancer screening and prevention programmes. The priority areas identified were: 1) breast cancer subtype-specific risk assessment tools applicable to women of all ancestries; 2) intermediate surrogate markers of response to preventive measures; 3) novel non-surgical preventive measures to reduce the incidence of breast cancer of poor prognosis; and 4) hybrid effectiveness–implementation research combined with modelling studies to evaluate the long-term population outcomes of risk-based early detection strategies. The implementation of such programmes would require health-care systems to be open to learning and adapting, the engagement of a diverse range of stakeholders and tailoring to societal norms and values, while also addressing the ethical and legal issues. In this Consensus Statement, we discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. Throughout, we highlight priorities for advancing each of these areas.
TL;DR: There are some grounds for optimism given the prospects for control of these cancers, with lip cancer incidence rates continuing to decrease for both sexes and the incidence rates of mouth cancer are also in decline in males, although increasing rates among females were observed in some populations.
Harvard University1, St. Jude Children's Research Hospital2, University of Toronto3, Dana Corporation4, Boston Children's Hospital5, University of London6, University College Hospital7, University College London8, University of Waterloo9, International Agency for Research on Cancer10, King's College London11, University of Queensland12, Cancer Council Queensland13, Homi Bhabha National Institute14, University of the Philippines Manila15, Universidad Francisco Marroquín16, McMaster University17, University of California, San Francisco18, National Institutes of Health19, Lund University20, American Childhood Cancer Organization21, Organisation for Economic Co-operation and Development22, Pontifical Catholic University of Chile23, Hacettepe University24, Cheikh Anta Diop University25, University of Valle26, University of Ghana27, Korle Bu Teaching Hospital28, Universidad Anáhuac México Norte29, National University of Singapore30
TL;DR: The burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.
Abstract: We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020–50 would be four times greater than the cumulative treatment costs of $594 billion, producing a net benefit of $1986 billion on the global investment: a net return of $3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.
TL;DR: Consumption of red and processed meat at an average level of 76 g/d that meets the current UK government recommendation was associated with an increased risk of colorectal cancer, whereas fibre from bread and breakfast cereals wasassociated with a reduced risk.
Abstract: Background Most of the previous studies on diet and colorectal cancer were based on diets consumed during the 1990s. Methods We used Cox-regression models to estimate adjusted hazard ratios for colorectal cancer by dietary factors in the UK Biobank study. Men and women aged 40-69 years at recruitment (2006-10) reported their diet on a short food-frequency questionnaire (n = 475 581). Dietary intakes were re-measured in a large sub-sample (n = 175 402) who completed an online 24-hour dietary assessment during follow-up. Trends in risk across the baseline categories were calculated by assigning re-measured intakes to allow for measurement error and changes in intake over time. Results During an average of 5.7 years of follow-up, 2609 cases of colorectal cancer occurred. Participants who reported consuming an average of 76 g/day of red and processed meat compared with 21 g/day had a 20% [95% confidence interval (CI): 4-37] higher risk of colorectal cancer. Participants in the highest fifth of intake of fibre from bread and breakfast cereals had a 14% (95% CI: 2-24) lower risk of colorectal cancer. Alcohol was associated with an 8% (95% CI: 4-12) higher risk per 10 g/day higher intake. Fish, poultry, cheese, fruit, vegetables, tea and coffee were not associated with colorectal-cancer risk. Conclusions Consumption of red and processed meat at an average level of 76 g/d that meets the current UK government recommendation (≤90 g/day) was associated with an increased risk of colorectal cancer. Alcohol was also associated with an increased risk of colorectal cancer, whereas fibre from bread and breakfast cereals was associated with a reduced risk.
Vanderbilt University Medical Center1, University of Copenhagen2, ICESI University3, Yale University4, BC Cancer Agency5, Mayo Clinic6, University of Paris-Sud7, University of Cambridge8, University of Leicester9, University of British Columbia10, University of Melbourne11, Peter MacCallum Cancer Centre12, Institut Gustave Roussy13, Edinburgh Cancer Research Centre14, Ontario Institute for Cancer Research15, University College Dublin16, University of Padua17, Curie Institute18, International Agency for Research on Cancer19, University of Bristol20, North Bristol NHS Trust21, University of São Paulo22, University of La Frontera23, Fudan University24, Kansai Medical University25, Lund University26, Netherlands Cancer Institute27, Cedars-Sinai Medical Center28, Northwestern University29, Indiana University – Purdue University Indianapolis30, Albert Einstein College of Medicine31, University of Milan32, Brigham and Women's Hospital33, Harvard University34, University of Auvergne35, National Institutes of Health36, Stanford University37, University of Texas MD Anderson Cancer Center38, University of Iowa Hospitals and Clinics39, Memorial Sloan Kettering Cancer Center40, University College Hospital41, Université libre de Bruxelles42, National Taiwan University43, University of Antwerp44, Ludwig Maximilian University of Munich45, Johns Hopkins University46, New York University47, Royal Brisbane and Women's Hospital48, Merck & Co.49, University Hospital of Giessen and Marburg50, Cornell University51, Bristol-Myers Squibb52
TL;DR: A risk‐management framework is proposed that may help mitigate the risks of suboptimal patient selection for immuno‐therapeutic approaches in clinical trials and daily practice based on combined TILs/PD‐L1 assessment in BC.
Abstract: Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin-stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.