Showing papers by "International Agency for Research on Cancer published in 2014"
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TL;DR: A “state of the science” review of current research into causes and risk factors for gliomas in adults is provided.
Abstract: Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors Although relatively rare, they cause significant mortality and morbidity Glioblastoma, the most common glioma histology (∼45% of all gliomas), has a 5-year relative survival of ∼5% A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome Genomic analyses of glioma have also produced new evidence about risk and prognosis Recently discovered biomarkers that indicate improved survival include O⁶-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine-phosphate-guanine island methylator phenotype Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma Many risk factors have been examined as potential contributors to glioma risk Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s) The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results We provide a “state of the science” review of current research into causes and risk factors for gliomas in adults
1,536 citations
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TL;DR: Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years, and provide 60-70% greater protection against invasive cervical carcinomas compared with cytology.
1,281 citations
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TL;DR: The complete SEQC data sets, comprising >100 billion reads, provide unique resources for evaluating RNA-seq analyses for clinical and regulatory settings, and measurement performance depends on the platform and data analysis pipeline, and variation is large for transcript-level profiling.
Abstract: We present primary results from the Sequencing Quality Control (SEQC) project, coordinated by the US Food and Drug Administration. Examining Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at multiple laboratory sites using reference RNA samples with built-in controls, we assess RNA sequencing (RNA-seq) performance for junction discovery and differential expression profiling and compare it to microarray and quantitative PCR (qPCR) data using complementary metrics. At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative expression are accurate and reproducible across sites and platforms if specific filters are used. In contrast, RNA-seq and microarrays do not provide accurate absolute measurements, and gene-specific biases are observed for all examined platforms, including qPCR. Measurement performance depends on the platform and data analysis pipeline, and variation is large for transcript-level profiling. The complete SEQC data sets, comprising >100 billion reads (10Tb), provide unique resources for evaluating RNA-seq analyses for clinical and regulatory settings.
853 citations
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TL;DR: The results of these analyses, and the decision of the IARC Working Group to classify PM and outdoor air pollution as carcinogenic (Group 1), further justify efforts to reduce exposures to air pollutants that can arise from many sources.
Abstract: Background: Particulate matter (PM) in outdoor air pollution was recently designated a Group I carcinogen by the International Agency for Research on Cancer (IARC). This determination was based on ...
744 citations
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TL;DR: HPV testing on a self-sample can be suggested as an additional strategy to reach women not participating in the regular screening programme, and some PCR-based HPV tests could be considered for routine screening after careful piloting assessing feasibility, logistics, population compliance, and costs.
Abstract: Summary Background Screening for human papillomavirus (HPV) infection is more effective in reducing the incidence of cervical cancer than screening using Pap smears. Moreover, HPV testing can be done on a vaginal sample self-taken by a woman, which offers an opportunity to improve screening coverage. However, the clinical accuracy of HPV testing on self-samples is not well-known. We assessed whether HPV testing on self-collected samples is equivalent to HPV testing on samples collected by clinicians. Methods We identified relevant studies through a search of PubMed, Embase, and CENTRAL. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: a cervical cell sample was self-collected by a woman followed by a sample taken by a clinician; a high-risk HPV test was done on the self-sample (index test) and HPV-testing or cytological interpretation was done on the specimen collected by the clinician (comparator tests); and the presence or absence of cervical intraepithelial neoplasia grade 2 (CIN2) or worse was verified by colposcopy and biopsy in all enrolled women or in women with one or more positive tests. The absolute accuracy for finding CIN2 or worse, or CIN grade 3 (CIN3) or worse of the index and comparator tests as well as the relative accuracy of the index versus the comparator tests were pooled using bivariate normal models and random effect models. Findings We included data from 36 studies, which altogether enrolled 154 556 women. The absolute accuracy varied by clinical setting. In the context of screening, HPV testing on self-samples detected, on average, 76% (95% CI 69–82) of CIN2 or worse and 84% (72–92) of CIN3 or worse. The pooled absolute specificity to exclude CIN2 or worse was 86% (83–89) and 87% (84–90) to exclude CIN3 or worse. The variation of the relative accuracy of HPV testing on self-samples compared with tests on clinician-taken samples was low across settings, enabling pooling of the relative accuracy over all studies. The pooled sensitivity of HPV testing on self-samples was lower than HPV testing on a clinician-taken sample (ratio 0·88 [95% CI 0·85–0·91] for CIN2 or worse and 0·89 [0·83–0·96] for CIN3 or worse). Also specificity was lower in self-samples versus clinician-taken samples (ratio 0·96 [0·95–0·97] for CIN2 or worse and 0·96 [0·93–0·99] for CIN3 or worse). HPV testing with signal-based assays on self-samples was less sensitive and specific than testing on clinician-based samples. By contrast, some PCR-based HPV tests generally showed similar sensitivity on both self-samples and clinician-based samples. Interpretation In screening programmes using signal-based assays, sampling by a clinician should be recommended. However, HPV testing on a self-sample can be suggested as an additional strategy to reach women not participating in the regular screening programme. Some PCR-based HPV tests could be considered for routine screening after careful piloting assessing feasibility, logistics, population compliance, and costs. Funding The 7th Framework Programme of the European Commission, the Belgian Foundation against Cancer, the International Agency for Research on Cancer, and the German Guideline Program in Oncology.
502 citations
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TL;DR: It is argued that primary prevention is a particularly effective way to fight cancer, with between a third and a half of cancers being preventable on the basis of present knowledge of risk factors.
500 citations
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Harvard University1, University of California, San Francisco2, Johns Hopkins University School of Medicine3, St. Jude Children's Research Hospital4, Emory University5, University of Cambridge6, Aix-Marseille University7, University of Texas MD Anderson Cancer Center8, Sapienza University of Rome9, Mayo Clinic10, University of Toronto11, University of Zurich12, Erasmus University Rotterdam13, University of Virginia14, The Chinese University of Hong Kong15, International Agency for Research on Cancer16, University of Münster17, University of Bonn18, Memorial Sloan Kettering Cancer Center19, Hacettepe University20, German Cancer Research Center21
TL;DR: The present “white paper” catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification of central nervous system tumors should follow a set of provided “ISN‐Haarlem” guidelines.
Abstract: Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present "white paper" catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided "ISN-Haarlem" guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be "layered" with histologic classification, WHO grade and molecular information listed below an "integrated diagnosis"; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors.
498 citations
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TL;DR: Limited, moderate quality evidence is provided that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations.
Abstract: Objectives To determine whether searching for Helicobacter pylori and treating with eradication therapy leads to a reduction in incidence of gastric cancer among healthy asymptomatic infected individuals.
Design Systematic review and meta-analysis of randomised controlled trials.
Data sources Medline, Embase, and the Cochrane central register of controlled trials were searched through to December 2013. Conference proceedings between 2001 and 2013 were hand searched. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions.
Eligibility criteria for selecting studies Randomised controlled trials examining the effect of at least seven days of eradication therapy on subsequent occurrence of gastric cancer in adults who tested positive for Helicobacter pylori but otherwise healthy and asymptomatic were eligible. The control arm had to receive placebo or no treatment. Subjects had to be followed for ≥2 years.
Main outcome measures Primary outcome, defined a priori, was the effect of eradication therapy on the subsequent occurrence of gastric cancer expressed as a relative risk of gastric cancer with 95% confidence intervals.
Results The search strategy identified 1560 citations, of which six individual randomised controlled trials were eligible. Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95), with no heterogeneity between studies (I2=0%, P=0.60). If the benefit of eradication therapy was assumed to persist lifelong the number needed to treat was as low as 15 for Chinese men and as high as 245 for US women.
Conclusions These data provide limited, moderate quality evidence that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations.
494 citations
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University of Cambridge1, MRC Human Nutrition Research2, University of Oxford3, Utrecht University4, Wageningen University and Research Centre5, Basque Government6, French Institute of Health and Medical Research7, Institut Gustave Roussy8, Lund University9, Umeå University10, Aarhus University11, University of Naples Federico II12, Aalborg University13, Prevention Institute14, University of Turin15, University of Granada16, Andalusian School of Public Health17, International Agency for Research on Cancer18, University of Murcia19, Imperial College London20
TL;DR: Different individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions, which suggests that SFAs are not homogeneous in their effects.
457 citations
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TL;DR: Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country, and two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function.
Abstract: Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide.
416 citations
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TL;DR: This is the first study examining Fusobacterium nucleatum (Fn) in the colonic tissue and stool of European CRC and CRA patients, and suggests Fn as a novel risk factor for disease progression from adenoma to cancer, possibly affecting patient survival outcomes.
Abstract: Commensal bacteria in the colon may play a role in colorectal cancer (CRC) development. Recent studies from North America showed that Fusobacterium nucleatum (Fn) infection is over-represented in disease tissue versus matched normal tissue in CRC patients. Using quantitative real-time polymerase chain reaction (qPCR) of DNA extracted from colorectal tissue biopsies and surgical resections of three European cohorts totalling 122 CRC patients, we found an over-abundance of Fn in cancerous compared to matched normal tissue (p < 0.0001). To determine whether Fn infection is an early event in CRC development, we assayed Fn in colorectal adenoma (CRA) tissue from 52 Irish patients. While for all CRAs the Fn level was not statistically significantly higher in disease versus normal tissue (p = 0.06), it was significantly higher for high-grade dysplasia (p = 0.015). As a secondary objective, we determined that CRC patients with low Fn levels had a significantly longer overall survival time than patients with moderate and high levels of the bacterium (p = 0.008). The investigation of Fn as a potential non-invasive biomarker for CRC screening showed that, while Fn was more abundant in stool samples from CRC patients compared to adenomas or controls, the levels in stool did not correlate with cancer or adenoma tissue levels from the same individuals. This is the first study examining Fn in the colonic tissue and stool of European CRC and CRA patients, and suggests Fn as a novel risk factor for disease progression from adenoma to cancer, possibly affecting patient survival outcomes. Our results highlight the potential of Fn detection as a diagnostic and prognostic determinant in CRC patients.
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Forschungszentrum Jülich1, University of Bonn2, German Center for Neurodegenerative Diseases3, University of Göttingen4, Heidelberg University5, Aarhus University6, University of Basel7, University of Würzburg8, Max Planck Society9, University of Liverpool10, University of Tübingen11, University of Duisburg-Essen12, Poznan University of Medical Sciences13, Nofer Institute of Occupational Medicine14, International Agency for Research on Cancer15, University of New South Wales16, Black Dog Institute17, Neuroscience Research Australia18, QIMR Berghofer Medical Research Institute19, Russian Academy20, Kursk State Medical University21, Russian Academy of Sciences22, Dalhousie University23, University of Toronto24, Montreal Neurological Institute and Hospital25, McGill University26, Université du Québec à Chicoutimi27
TL;DR: Results from the largest BD GWAS to date are presented by investigating 2.3 million single-nucleotide polymorphisms (SNPs) in a sample of 24,025 patients and controls and detecting 56 genome-wide significant SNPs in five chromosomal regions including previously reported risk loci ANK3, ODZ4 and TRANK1.
Abstract: Bipolar disorder (BD) is a common and highly heritable mental illness and genome-wide association studies (GWAS) have robustly identified the first common genetic variants involved in disease aetiology. The data also provide strong evidence for the presence of multiple additional risk loci, each contributing a relatively small effect to BD susceptibility. Large samples are necessary to detect these risk loci. Here we present results from the largest BD GWAS to date by investigating 2.3 million single-nucleotide polymorphisms (SNPs) in a sample of 24,025 patients and controls. We detect 56 genome-wide significant SNPs in five chromosomal regions including previously reported risk loci ANK3, ODZ4 and TRANK1, as well as the risk locus ADCY2 (5p15.31) and a region between MIR2113 and POU3F2 (6q16.1). ADCY2 is a key enzyme in cAMP signalling and our finding provides new insights into the biological mechanisms involved in the development of BD.
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International Agency for Research on Cancer1, deCODE genetics2, National Institutes of Health3, University of Toronto4, German Cancer Research Center5, Harvard University6, Dartmouth College7, University Health Network8, American Cancer Society9, University of Texas MD Anderson Cancer Center10, Russian Academy11, Nofer Institute of Occupational Medicine12, Curie Institute13, Charles University in Prague14, Norwegian University of Science and Technology15, Fred Hutchinson Cancer Research Center16, French Institute of Health and Medical Research17, University of Tartu18, University of Bergen19, University of Geneva20, Pomeranian Medical University21, Imperial College London22, Institut Gustave Roussy23, Utrecht University24, Academy of Athens25, University of Cambridge26, Umeå University27, University of Tromsø28, Council on Education for Public Health29, Baylor College of Medicine30, Heidelberg University31, University of Göttingen32, Cambridge University Hospitals NHS Foundation Trust33
TL;DR: The analysis demonstrates that imputation can identify rare disease-causing variants with substantive effects on cancer risk from preexisting genome-wide association study data and provides further evidence for inherited genetic susceptibility to lung cancer and its biological basis.
Abstract: We conducted imputation to the 1000 Genomes Project of four genome-wide association studies of lung cancer in populations of European ancestry (11,348 cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295 controls for follow-up. We identified large-effect genome-wide associations for squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds ratio (OR) = 2.47, P = 4.74 x 10(-20)) and CHEK2 p.Ile157Thr (rs17879961, OR = 0.38, P = 1.27 x 10(-13)). We also showed an association between common variation at 3q28 (TP63, rs13314271, OR = 1.13, P = 7.22 x 10(-10)) and lung adenocarcinoma that had been previously reported only in Asians. These findings provide further evidence for inherited genetic susceptibility to lung cancer and its biological basis. Additionally, our analysis demonstrates that imputation can identify rare disease-causing variants with substantive effects on cancer risk from preexisting genome-wide association study data.
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TL;DR: Additional research is necessary to characterize the biology and epidemiology of the vast number of HPV types that have been poorly investigated so far, with a final aim of clarifying their potential roles in other human diseases.
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TL;DR: The continuing rise in lung cancer among women in many countries reinforces the need for targeted smoking cessation efforts alongside preventive actions.
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TL;DR: Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment.
Abstract: Background The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed. Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD. Methods We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012. Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence. Results 86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both. Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence. Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low. As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence. Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence. Conclusions Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment.
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Harvard University1, German Cancer Research Center2, Fred Hutchinson Cancer Research Center3, Mayo Clinic4, National Institutes of Health5, New York University6, University of California, San Francisco7, University of Toronto8, Monash University9, American Cancer Society10, Group Health Cooperative11, Johns Hopkins University12, University of Hawaii at Manoa13, University of Texas MD Anderson Cancer Center14, Carlos III Health Institute15, Memorial Sloan Kettering Cancer Center16, Yale University17, University at Buffalo18, University of Washington19, Vanderbilt University20, Institut Gustave Roussy21, Westat22, Heidelberg University23, Utrecht University24, Sapienza University of Rome25, University of Liverpool26, University of Pisa27, Veterans Health Administration28, University of Minnesota29, University of Southern California30, Mercy Medical Center (Baltimore, Maryland)31, University of North Carolina at Chapel Hill32, International Agency for Research on Cancer33, University of Oxford34, University of Cambridge35, Cleveland Clinic36, Lithuanian University of Health Sciences37, National Institute for Health and Welfare38, University of Melbourne39, University of Tokyo40, Duke University41, Imperial College London42, University of Bologna43, Casa Sollievo della Sofferenza44, Pompeu Fabra University45, Autonomous University of Barcelona46, Umeå University47, Medical University of Łódź48, Academy of Sciences of the Czech Republic49
TL;DR: This study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies and an independent signal in exon 2 of TERT at the established region 5p15.
Abstract: We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.
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TL;DR: It is suggested that percentage dense area is a stronger breast cancer risk factor than absolute dense area, but it is unclear whether the association is independent ofabsolute dense area.
Abstract: Results Among premenopausal women (n = 1776 case patients; n = 2834 control subjects), summary odds ratios were 1.37 (95% CI = 1.29 to 1.47) for absolute dense area, 0.78 (95% CI = 0.71 to 0.86) for absolute nondense area, and 1.52 (95% CI = 1.39 to 1.66) for percentage dense area when pooling estimates adjusted for age, body mass index, and parity. Corresponding odds ratios among postmenopausal women (n = 6643 case patients; n = 11 187 control subjects) were 1.38 (95% CI = 1.31 to 1.44), 0.79 (95% CI = 0.73 to 0.85), and 1.53 (95% CI = 1.44 to 1.64). After additional adjustment for absolute dense area, associations between absolute nondense area and breast cancer became attenuated or null in several studies and summary odds ratios became 0.82 (95% CI = 0.71 to 0.94; Pheterogeneity = .02) for premenopausal and 0.85 (95% CI = 0.75 to 0.96; Pheterogeneity < .01) for postmenopausal women. Conclusions The results suggest that percentage dense area is a stronger breast cancer risk factor than absolute dense area. Absolute nondense area was inversely associated with breast cancer risk, but it is unclear whether the association is independent of absolute dense area.
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National Institutes of Health1, Mayo Clinic2, City of Hope National Medical Center3, University of New South Wales4, University of Alabama5, University of California, San Francisco6, Karolinska Institutet7, University of Chicago8, Yale University9, University of Bordeaux10, Macquarie University11, University of Paris-Sud12, Harvard University13, Stanford University14, Exponent15, Uppsala University16, Statens Serum Institut17, University of Florence18, Imperial College London19, German Cancer Research Center20, Icahn School of Medicine at Mount Sinai21, International Agency for Research on Cancer22, University of Cagliari23, University of Burgundy24, University of Freiburg25, Dublin City University26, University of Southern California27, Fred Hutchinson Cancer Research Center28, University of Washington29, Drexel University30, Wayne State University31, University of York32, Simon Fraser University33, University of British Columbia34, University of Sydney35, University of Milan36, Mario Negri Institute for Pharmacological Research37, University of Rochester38, Cancer Prevention Institute of California39, Emory University40, Roger Williams Medical Center41, Boston University42
TL;DR: Using a novel approach to investigate etiologic heterogeneity among NHL subtypes,risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes are identified, suggesting both subtype-specific and shared underlying mechanisms.
Abstract: Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy and the fifth most common type of cancer in more developed regions of the world (1). Numerous NHL subtypes with distinct combinations of morphologic, immunophenotypic, genetic, and clinical features are currently recognized (2,3). The incidence of NHL subtypes varies substantially by age, sex, and race/ethnicity (4–7). However, the etiological implications of this biological, clinical, and epidemiological diversity are incompletely understood.
The importance of investigating etiology by NHL subtype is clearly supported by research on immunosuppression, infections, and autoimmune diseases, which are the strongest and most established risk factors for NHL. Studies of solid organ transplant recipients and individuals infected with HIV demonstrate that risks are markedly increased for several—but not all—NHL subtypes (8–13). Some infections and autoimmune diseases are associated with a single specific subtype [eg, human T-cell lymphotropic virus, type I (HTLV-I) with adult T-cell leukemia/lymphoma (14), celiac disease with enteropathy-type peripheral T-cell lymphoma (PTCL) (15–17)], whereas others [eg, Epstein–Barr virus, hepatitis C virus (HCV), Sjogren’s syndrome (18–21)] have been associated with multiple subtypes.
In the last two decades, reports from individual epidemiological studies of NHL have suggested differences in risks among NHL subtypes for a wide range of risk factors, but most studies have lacked the statistical power to assess any differences quantitatively and have not systematically evaluated combinations of subtypes. One study assessed multiple risk factors and found support for both etiologic commonality and heterogeneity for NHL subtypes, with risk factor patterns suggesting that immune dysfunction is of greater etiologic importance for diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma than for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (22). However, that analysis was limited to approximately 1300 NHL cases and considered only the four most common NHL subtypes. Pooling data from multiple studies through the International Lymphoma Epidemiology Consortium (InterLymph) have provided substantial insight into associations between specific risk factors and NHL subtypes, with evidence that family history of hematologic malignancy, autoimmune diseases, atopic conditions, lifestyle factors (smoking, alcohol, anthropometric measures, and hair dye use), and sun exposure are associated with NHL risk (19,21,23–32). However, no previous study has compared patterns of risk for a range of exposures for both common and rarer NHL subtypes.
We undertook the InterLymph NHL Subtypes Project, a pooled analysis of 20 case–control studies including 17 471 NHL cases and 23 096 controls, to advance understanding of NHL etiology by investigating NHL subtype-specific risks associated with medical history, family history of hematologic malignancy, lifestyle factors, and occupation. The detailed risk factor profiles for each of 11 NHL subtypes appear in this issue (15–17,33–40). In this report, we assess risk factor heterogeneity among the NHL subtypes and identify subtypes that have similar risk factor profiles.
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TL;DR: With the number of annual cancer cases and deaths likely to increase by at least 70% by 2030, there is a pressing need for a coordinated approach to improving the extent and quality of services for cancer control in Africa, and better surveillance systems with which they can be planned and monitored.
Abstract: Background:Non-communicable diseases, and especially cancers, are recognized as an increasing problem for low- and middle income countries. Effective control programmes require adequate information on the size, nature, and evolution of the health problem which they pose. Methods:We present estimates of the incidence and mortality of cancer in Africa in 2012, derived from "Globocan 2012", published by the International Agency for Research on Cancer. Results: There were 847,000 new cancer cases (6% of the world total) and 591,000 deaths (7.2% of the world total) in the 54 countries of Africa in 2012. While the cancer profiles often differ markedly between regions, the most common cancers in men were prostate (16.4% of new cancers), liver (10.7%) and Kaposi sarcoma (6.7%); in women, by far the most important are cancers of the breast (27.6% of all cancers) and cervix uteri (20.4%). Conclusions: These results are based on the best data currently available, and provide a reasonable appraisal of the cancer situation in Africa. With the number of annual cancer cases and deaths likely to increase by at least 70% by 2030 there is a pressing need for a coordinated approach to improving the extent and quality of services for cancer control in Africa, and better surveillance systems with which they can be planned and monitored. Impact:The need for developing cancer surveillance systems in Africa for planning and monitoring cancer prevention and control in the region.
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TL;DR: The evaluation by IARC indicates both the need for further research into the cancer risks associated with exposure to air pollution in China and the urgent need to act to reduce exposure to the population.
Abstract: The International Agency for Research on Cancer (IARC) has classified outdoor air pollution and the particulate matter (PM) in outdoor air pollution as carcinogenic to humans, as based on sufficient evidence of carcinogenicity in humans and experimental animals and strong support by mechanistic studies. The data with important contributions to the evaluation are reviewed, highlighting the data with particular relevance to China, and implications of the evaluation with respect to China are discussed. The air pollution levels in Chinese cities are among the highest observed in the world today and frequently exceed health-based national and international guidelines. Data from high-quality epidemiologic studies in Asia, Europe, and North America consistently show positive associations between lung cancer and PM exposure and other indicators of air pollution, which persist after adjustment for important lung cancer risk factors, such as tobacco smoking. Epidemiologic data from China are limited but nevertheless indicate an increased risk of lung cancer associated with several air pollutants. Excess cancer risk is also observed in experimental animals exposed to polluted outdoor air or extracted PM. The exposure of several species to outdoor air pollution is associated with markers of genetic damage that have been linked to increased cancer risk in humans. Numerous studies from China, especially genetic biomarker studies in exposed populations, support that the polluted air in China is genotoxic and carcinogenic to humans. The evaluation by IARC indicates both the need for further research into the cancer risks associated with exposure to air pollution in China and the urgent need to act to reduce exposure to the population.
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TL;DR: Implementation of VIA screening in several LMICs is conducive to future HPV screening programs when affordable HPV tests become widely available, and both HPV vaccination and HPV screening have a huge potential to eliminate cervical cancer in LM ICs.
Abstract: Background Screening programs involve testing asymptomatic individuals with an accurate screening test to identify those likely to have the disease of interest and to further investigate them to confirm or exclude the disease. The aim of cancer screening is to prevent cancer deaths and improve quality of life by finding cancers early and by effectively treating them. A decision to introduce a screening program in public health services depends on the evidence that the benefits outweigh the harms of screening, disease burden, availability of suitable screening test, effective treatment, adequate resources, and efficient health services. Screening programs should achieve high participation for testing, diagnosis, and treatment to be effective and efficient. Objective To describe the current status of cancer screening programs in low- and middle-income countries (LMICs). Method A review of literature and on-going cancer screening initiatives in LMICs was made to discuss cancer screening in these countries. Findings Although population-based programs offering Papanicolaou testing every 3 to 5 years have reduced cervical cancer incidence and mortality in high-income countries, such programs have been less successful in reducing cervical cancer burden in LMICs due to poor organization, lack of coverage, and lack of quality assurance. The challenges in introducing high-quality cytology screening in LMICs have led to evaluation of alternative screening approaches such as visual inspection with acetic acid (VIA), human papillomavirus (HPV) testing-based screening, and novel paradigms such as a “single-visit screen and treat” in which treatment with cryotherapy or cold coagulation is provided to screen-positive women without clinical evidence of cancer. Both HPV testing and VIA have been found to prevent cervical neoplasia and cervical cancer deaths in clinical trials. Although mammography screening reduces breast cancer mortality, associated overdiagnosis and overtreatment and the balance between benefits and harms have received much attention in recent years. Although introduction of clinical breast examination screening in LMICs should wait for evidence from ongoing trials, improving breast awareness and access to early diagnosis and treatment in health services is a valuable breast cancer control option in LMICs. Organized colorectal cancer screening programs are still evolving and are in early stages of development in many high-income countries. To date, there is insufficient evidence to support the introduction of population-based stomach, lung, ovarian, and prostate cancer screening in public health services. Conclusions Implementation of VIA screening in several LMICs is conducive to future HPV screening programs when affordable HPV tests become widely available. Both HPV vaccination and HPV screening have a huge potential to eliminate cervical cancer in LMICs. A mammography screening program is a complex undertaking involving substantial resources and infrastructure that may not be feasible in many LMICs.
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Mario Negri Institute for Pharmacological Research1, University of Texas MD Anderson Cancer Center2, National Institutes of Health3, Mayo Clinic4, University of California, San Francisco5, QIMR Berghofer Medical Research Institute6, Pennsylvania State University7, University of Toronto8, Memorial Sloan Kettering Cancer Center9, Imperial College London10, International Agency for Research on Cancer11, Palacký University, Olomouc12, Charles University in Prague13, National and Kapodistrian University of Athens14, University of Florence15, University of Texas at Austin16, Boston Children's Hospital17, Masaryk University18, Louisiana State University19, University of Minnesota20, European Institute of Oncology21, Harvard University22, Icahn School of Medicine at Mount Sinai23, University of Milan24
TL;DR: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics and shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in Pancreatic cancer.
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TL;DR: It is found that testicular cancer is becoming more common in low- and middle-income countries, where the optimal treatment might not yet be available and mortality rates are stable or increasing.
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International Agency for Research on Cancer1, National Autonomous University of Mexico2, McGill University3, Jewish General Hospital4, Council on Education for Public Health5, Claude Bernard University Lyon 16, St. Joseph Hospital7, François Rabelais University8, University of Strasbourg9, University of Caen Lower Normandy10
TL;DR: Next-generation sequencing on circulating free DNA samples obtained from a consecutive series of patients for the screening of a range of clinically relevant mutations demonstrates the feasibility and potential utility of mutation screening in cfDNA using IonTorrent NGS for the detection of arange of tumor biomarkers in patients with metastatic lung cancer.
Abstract: PURPOSE: Tumor somatic mutation analysis is part of the standard management of metastatic lung cancer. However, physicians often have to deal with small biopsies and consequently with challenging mutation testing. Circulating-free DNA (cfDNA) is a promising tool for accessing the tumor genome as a liquid biopsy. Here we evaluated next generation sequencing (NGS) on cfDNA samples obtained from a consecutive series of patients for the screening of a range of clinically relevant mutations.
METHOD: One hundred seven plasma samples were collected from the BioCAST / IFCT-1002 lung cancer study (never-smokers cohort). Matched tumor DNA (tDNA) was obtained for 68 cases. Multiplex PCR-based assays were designed to target specific coding regions in EGFR, KRAS, BRAF, ERBB2 and PI3KCA genes and amplicon sequencing was performed at deep coverage on the cfDNA/tDNA pairs using the NGS IonTorrent PGM Platform.
RESULTS: CfDNA concentration in plasma was significantly associated with both stage and number of metastatic sites. In tDNA, 50 mutations (36 EGFR, 5 ERBB2, 4 KRAS, 3 BRAF, and 2 PIK3CA) were identified, of which 26 were detected in cfDNA. Sensitivity of the test was 58% [95%CI: 43%-71%] and the estimated specificity was 87% [62%-96%].
CONCLUSION: These data demonstrate the feasibility and potential utility of mutation screening in cfDNA using IonTorrent NGS for the detection of a range of tumor biomarkers in patients with metastatic lung cancer.
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University of Cambridge1, Lund University2, Wellcome Trust Sanger Institute3, Imperial College London4, University of Helsinki5, University of Southern Denmark6, Health Science University7, Carlos III Health Institute8, Wellcome Trust Centre for Human Genetics9, University of Paris-Sud10, German Cancer Research Center11, University of Oxford12, Harvard University13, Aalborg University14, Prevention Institute15, University of Naples Federico II16, Umeå University17, University of Turin18, Andalusian School of Public Health19, International Agency for Research on Cancer20, Utrecht University21
TL;DR: The authors found that the relative effect of a type 2 diabetes genetic risk score is greater in younger and leaner participants, and the high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.
Abstract: Background: Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. Methods and Findings: The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prenticeweighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction = 1.20610 24 ). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction = 1.50610 23 ) and waist circumference (p for interaction = 7.49610 29 ). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. Conclusions: The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this subgroup is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention. Please see later in the article for the Editors’ Summary.
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TL;DR: Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which were missing in the literature that were reviewed.
Abstract: This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world's agriculture, were missing in the literature that were reviewed
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TL;DR: Fully-automated methods are valid alternatives to the labour-intensive "gold standard" Cumulus for quantifying density in FFDM and showed that percent density was inversely associated with age, BMI, being parous and postmenopausal at mammography.
Abstract: Introduction: Mammographic density is a strong breast cancer risk factor and a major determinant of screening sensitivity. However, there is currently no validated estimation method for full-field digital mammography (FFDM). Methods: The performance of three area-based approaches (BI-RADS, the semi-automated Cumulus, and the fully-automated ImageJ-based approach) and three fully-automated volumetric methods (Volpara, Quantra and single energy x-ray absorptiometry (SXA)) were assessed in 3168 FFDM images from 414 cases and 685 controls. Linear regression models were used to assess associations between breast cancer risk factors and density among controls, and logistic regression models to assess density-breast cancer risk associations, adjusting for age, body mass index (BMI) and reproductive variables. Results: Quantra and the ImageJ-based approach failed to produce readings for 4% and 11% of the participants. All six density assessment methods showed that percent density (PD) was inversely associated with age, BMI, being parous and postmenopausal at mammography. PD was positively associated with breast cancer for all methods, but with the increase in risk per standard deviation increment in PD being highest for Volpara (1.83; 95% CI: 1.51 to 2.21) and Cumulus (1.58; 1.33 to 1.88) and lower for the ImageJ-based method (1.45; 1.21 to 1.74), Quantra (1.40; 1.19 to 1.66) and SXA (1.37; 1.16 to 1.63). Women in the top PD quintile (or BI-RADS 4) had 8.26 (4.28 to 15.96), 3.94 (2.26 to 6.86), 3.38 (2.00 to 5.72), 2.99 (1.76 to 5.09), 2.55 (1.46 to 4.43) and 2.96 (0.50 to 17.5) times the risk of those in the bottom one (or BI-RADS 1), respectively, for Volpara, Quantra, Cumulus, SXA, ImageJ-based method, and BI-RADS (P for trend <0.0001 for all). The ImageJ-based method had as lightly higher ability to discriminate between cases and controls (area under the curve (AUC) for PD = 0.68, P = 0.05), and Quantra slightly lower (AUC = 0.63; P = 0.06), than Cumulus (AUC = 0.65). Conclusions: Fully-automated methods are valid alternatives to the labour-intensive “gold standard” Cumulus for quantifying density in FFDM. The choice of a particular method will depend on the aims and setting but the same approach will be required for longitudinal density assessments.
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TL;DR: Key research challenges include understanding oral HPV transmission and male predominance, clarifying the role of cofactors, and developing new screening and treatment methods for HPV‐associated HNSCC.
Abstract: The EUROGIN 2012 roadmap is focused on the comparative epidemiology of human papillomavirus (HPV) associated head and neck squamous cell cancers (HNSCC) and cervical cancers. Discussed are the similarities and differences between the two cancers with regard to global disease burden, HPV prevalence and type distribution, disease cofactors, molecular pathogenesis, treatment approaches, prognostic factors and primary and secondary prevention. The global incidence of HNSCC and cervical cancer is similar; however, a minority of HNSCC in comparison to virtually all cervical cancers is caused by HPV. HPV infection prevalence is considerably lower in the oral than genital regions for reasons that are as yet unclear. Infection at both sites is strongly associated with sexual behavior, but this association does not appear to explain the male predominance of oral HPV infection. Studies of the molecular pathogenesis of HPV-associated HNSCC (predominantly oropharyngeal cancers) are hampered by the lack of a readily detectable intermediate clinical endpoint analogous to cervix intraepithelial neoplasia. Nevertheless, similarities in chromosomal aberrations, gene expression, methylation and microRNA profiles between HPV-positive HNSCC and cervical cancer argue for shared carcinogenic pathways. Treatment approaches to oropharyngeal and cervical cancers are remarkably similar, with the development of HPV-targeted therapies as the ultimate treatment goal. Key research challenges include understanding oral HPV transmission and male predominance, clarifying the role of cofactors, and developing new screening and treatment methods for HPV-associated HNSCC.