95 results on '"Hilde, Langseth"'
Search Results
2. Dynamic and static circulating cancer microRNA biomarkers – a validation study
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Masood Abu-Halima, Andreas Keller, Lea Simone Becker, Ulrike Fischer, Annika Engel, Nicole Ludwig, Fabian Kern, Trine B. Rounge, Hilde Langseth, Eckart Meese, and Verena Keller
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microrna ,cancer ,colon cancer ,breast cancer ,biomarker ,mir-99a ,mir-155 ,Genetics ,QH426-470 - Abstract
For cancers and other pathologies, early diagnosis remains the most promising path to survival. Profiling of longitudinal cohorts facilitates insights into trajectories of biomarkers. We measured microRNA expression in 240 serum samples from patients with colon, lung, and breast cancer and from cancer-free controls. Each patient provided at least two serum samples, one prior to diagnosis and one following diagnosis. The median time interval between the samples was 11.6 years. Using computational models, we evaluated the circulating profiles of 21 microRNAs. The analysis yielded two sets of biomarkers, static ones that show an absolute difference between certain cancer types and controls and dynamic ones where the level over time provided higher diagnostic information content. In the first group, miR-99a-5p stands out for all three cancer types. In the second group, miR-155-5p allows to predict lung cancers and colon cancers. Classification in samples from cancer and non-cancer patients using gradient boosted trees reached an average accuracy of 79.9%. The results suggest that individual change over time or an absolute value at one time point may predict a disease with high specificity and sensitivity.
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- 2023
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3. Janus serumbank – jakten på biomarkører for kreft
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Hilde Langseth, Kristina Kymre, Tove Slyngstad, Trine B. Rounge, Randi E. Gislefoss, and Marianne Lauritzen
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Public aspects of medicine ,RA1-1270 - Abstract
Janus is a population-based prospective cancer biobank established in 1973. The biobank consists of residual blood serum samples from more than 300 000 men and women, who participated in different health surveys in Norway or as Red Cross blood donors during the period 1972–2004. It was established on the initiative of Professor of Pathology, Olav Torgersen (1907–78), referring to the longstanding maxim that ‘prevention is better than cure’. The purpose of the biobank was to build up a resource for studies of cancer aetiology and early detection of cancer, by measuring biochemical and immunological changes several years before the patient’s diagnosis. The Janus cohort, with comprehensive registry-based follow-up, enables longitudinal assessment of the preclinical stage in cancer patients or the latent period before the tumour has been established, and is ideal for the search of novel biomarkers of cancer. The Cancer Registry of Norway took over the cohort in 2004. In 2019 the biobank was moved into new semi-automated storage facilities and all samples were barcoded. The biobank is annually linked to the Cancer Registry for updates on new cancer cases and by the end of 2020 the number of incident cancer cases in Janus was 107 366. A continuous work in Janus has been on quality assurance of the biospecimens by investigating sample quality parameters like the effect of different pre-processing of the samples as well as storage time and temperature. We have investigated the stability of various hormones, proteins, metabolites, electrolytes and RNAs. This work has contributed to important knowledge in establishing Good Biobank Practice in Norway. In recent years we have also shown that the trace amounts of DNA in Janus is of sufficient quality for genotyping and methylation studies. Today Janus is used in a large number of national and international studies and is an active part in several international cancer consortia. The scientific output from the biobank contains a substantial proportion of high impact papers that have contributed to increased knowledge on cancer biomarkers for use in cancer control. Many of the projects have focused on investigating the association between infections and cancer, environmental exposures and cancer and early detection biomarkers. In recent years we have identified RNAs as early detection and potentially screening biomarkers of cancer. We have developed and optimized an RNA sequencing method for samples with low input RNA and produced RNA profiles of pre-clinical samples from 1631 cancer patients and 673 cancer-free controls. The sequencing data is combined with detailed cancer information from the Cancer Registry of Norway and information on environmental exposures from health surveys, in advanced biocomputational analysis. Results published on the healthy control group shows that RNA expression levels are significantly affected by age and smoking. For lung cancer the results showed dynamic changes in differentially expressed circulating RNAs specific to histology and stage. In the future we aim to utilize Janus in omics analyses and produce large scale datasets that can be shared and used in many research projects.
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- 2022
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4. Editorial: Insights in life-course epidemiology and social inequalities: 2021
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Cyrille Delpierre and Hilde Langseth
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social determinants ,quality data ,methodological approaches ,life-course epidemiology ,social inequalities ,Public aspects of medicine ,RA1-1270 - Published
- 2022
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5. Serum RNAs can predict lung cancer up to 10 years prior to diagnosis
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Sinan U Umu, Hilde Langseth, Verena Zuber, Åslaug Helland, Robert Lyle, and Trine B Rounge
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lung cancer ,biomarker ,RNA ,prediagnostic samples ,human serum ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Lung cancer (LC) prognosis is closely linked to the stage of disease when diagnosed. We investigated the biomarker potential of serum RNAs for the early detection of LC in smokers at different prediagnostic time intervals and histological subtypes. In total, 1061 samples from 925 individuals were analyzed. RNA sequencing with an average of 18 million reads per sample was performed. We generated machine learning models using normalized serum RNA levels and found that smokers later diagnosed with LC in 10 years can be robustly separated from healthy controls regardless of histology with an average area under the ROC curve (AUC) of 0.76 (95% CI, 0.68–0.83). Furthermore, the strongest models that took both time to diagnosis and histology into account successfully predicted non-small cell LC (NSCLC) between 6 and 8 years, with an AUC of 0.82 (95% CI, 0.76–0.88), and SCLC between 2 and 5 years, with an AUC of 0.89 (95% CI, 0.77–1.0), before diagnosis. The most important separators were microRNAs, miscellaneous RNAs, isomiRs, and tRNA-derived fragments. We have shown that LC can be detected years before diagnosis and manifestation of disease symptoms independently of histological subtype. However, the highest AUCs were achieved for specific subtypes and time intervals before diagnosis. The collection of models may therefore also predict the severity of cancer development and its histology. Our study demonstrates that serum RNAs can be promising prediagnostic biomarkers in an LC screening setting, from early detection to risk assessment.
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- 2022
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6. A 10‐year prediagnostic follow‐up study shows that serum RNA signals are highly dynamic in lung carcinogenesis
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Sinan Uğur Umu, Hilde Langseth, Andreas Keller, Eckart Meese, Åslaug Helland, Robert Lyle, and Trine B. Rounge
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lung cancer ,NSCLC ,prediagnostic serum ,RNA dynamics ,RNA‐seq ,SCLC ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The majority of lung cancer (LC) patients are diagnosed at a late stage, and survival is poor. Circulating RNA molecules are known to have a role in cancer; however, their involvement before diagnosis remains an open question. In this study, we investigated circulating RNA dynamics in prediagnostic LC samples, focusing on smokers, to identify if and when disease‐related signals can be detected in serum. We sequenced small RNAs in 542 serum LC samples donated up to 10 years before diagnosis and 519 matched cancer‐free controls coming from 905 individuals in the Janus Serum Bank. This sample size provided sufficient statistical power to independently analyze time to diagnosis, stage, and histology. The results showed dynamic changes in differentially expressed circulating RNAs specific to LC histology and stage. The greatest number of differentially expressed RNAs was identified around 7 years before diagnosis for early‐stage LC and 1–4 years prior to diagnosis for locally advanced and advanced‐stage LC, regardless of LC histology. Furthermore, NSCLC and SCLC histologies have distinct prediagnostic signals. The majority of differentially expressed RNAs were associated with cancer‐related pathways. The dynamic RNA signals pinpointed different phases of tumor development over time. Stage‐specific RNA profiles may be associated with tumor aggressiveness. Our results improve the molecular understanding of carcinogenesis. They indicate substantial opportunity for screening and improved treatment and will guide further research on early detection of LC. However, the dynamic nature of the RNA signals also suggests challenges for prediagnostic biomarker discovery.
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- 2020
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7. Pre-diagnostic serum concentrations of organochlorines and risk of acute myeloid leukemia: A nested case-control study in the Norwegian Janus Serum Bank Cohort
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Bryan A. Bassig, Lawrence S. Engel, Hilde Langseth, Tom K. Grimsrud, Kenneth P. Cantor, Roel Vermeulen, Mark P. Purdue, Dana Boyd Barr, Jason Y.Y. Wong, Aaron Blair, Nathaniel Rothman, and Qing Lan
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Environmental sciences ,GE1-350 - Abstract
Background: Epidemiologic studies suggest an increased risk of leukemia among individuals occupationally exposed to some organochlorine (OC) compounds. Associations between serum OC pesticide and polychlorinated biphenyl (PCB) levels and risk of acute myeloid leukemia (AML), the most common subtype of acute leukemia in adult populations, have not been evaluated prospectively in the general population. Objective: We evaluated the risk of AML in relation to pre-diagnostic serum levels of OC pesticides and PCBs in a case-control study nested within the Janus Serum Bank Cohort. Methods: Janus is a large population-based cohort containing biologic samples collected beginning in the early 1970s from ~318,000 individuals in Norway. Serum levels of 11 OC pesticides or their metabolites and 34 PCB congeners were measured in 56 AML cases and 288 controls. Conditional logistic regression was conducted to evaluate associations between lipid-adjusted serum OC levels and risk of AML. Results: Higher serum levels of total chlordane/heptachlor metabolites were associated with AML risk (3rd vs. 1st tertile odds ratio (OR) = 2.26, 95% confidence interval (CI) = 0.91–5.63; ptrend = 0.11). Significant exposure-response associations were observed for levels of heptachlor epoxide (3rd vs. 1st tertile OR = 2.85, 95% CI = 1.05–7.73; ptrend = 0.02) and dieldrin (3rd vs. 1st tertile OR = 2.71, 95% CI = 1.07–6.83; ptrend = 0.03). No significant exposure-response associations with AML risk were observed for total DDT or individual isomers and derivatives. Higher serum levels of p,p′-DDT showed a non-significant increase in risk, but the exposure-response became attenuated when co-adjusting for heptachlor epoxide or dieldrin levels. Serum PCB levels were not significantly associated with AML risk. Conclusions: Our data suggest that higher serum levels of dieldrin and metabolites derived from chlordane/heptachlor are associated with risk of AML in the general Norwegian population, based on samples collected on average ~17 years before diagnosis. Further research in populations with historically high or recent exposure to DDT is warranted to assess the association with AML risk with body burden of specific DDT isomers and derivatives. Keywords: Acute myeloid leukemia, Organochlorines, Pesticides, Polychlorinated biphenyls
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- 2019
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8. Serum RNA Profiling in the 10-Years Period Prior to Diagnosis of Testicular Germ Cell Tumor
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Joshua Burton, Sinan U. Umu, Hilde Langseth, Tom Grotmol, Tom K. Grimsrud, Trine B. Haugen, and Trine B. Rounge
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RNA profiling ,serum ,testicular cancer ,pre-diagnostic ,seminoma ,non-seminoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Although testicular germ cell tumor (TGCT) overall is highly curable, patients may experience late effects after treatment. An increased understanding of the mechanisms behind the development of TGCT may pave the way for better outcome for patients. To elucidate molecular changes prior to TGCT diagnosis we sequenced small RNAs in serum from 69 patients who were later diagnosed with TGCT and 111 matched controls. The deep RNA profiles, with on average 18 million sequences per sample, comprised of nine classes of RNA, including microRNA. We found that circulating RNA signals differed significantly between cases and controls regardless of time to diagnosis. Different levels of TSIX related to X-chromosome inactivation and TEX101 involved in spermatozoa production are among the interesting findings. The RNA signals differed between seminoma and non-seminoma TGCT subtypes, with seminoma cases showing lower levels of RNAs and non-seminoma cases showing higher levels of RNAs, compared with controls. The differentially expressed RNAs were typically associated with cancer related pathways. Our results indicate that circulating RNA profiles change during TGCT development according to histology and may be useful for early detection of this tumor type.
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- 2020
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9. A high-resolution map of the human small non-coding transcriptome.
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Tobias Fehlmann, Christina Backes, Julia Alles, Ulrike Fischer, Martin Hart, Fabian Kern, Hilde Langseth, Trine Rounge, Sinan Ugur Umu, Mustafa Kahraman, Thomas Laufer, Jan Haas, Cord Staehler, Nicole Ludwig 0001, Matthias Hübenthal, Benjamin Meder, Andre Franke, Hans-Peter Lenhof, Eckart Meese, and Andreas Keller
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- 2018
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10. Characterization of ovarian cancer survival by histotype and stage: A nationwide study in Norway
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Renée Turzanski Fortner, Cassia B. Trewin‐Nybråten, Torbjørn Paulsen, and Hilde Langseth
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Cancer Research ,Oncology - Published
- 2023
11. Cohort Profile
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Katie M. O'Brien, Michael J. Orlich, Alpa V. Patel, Kim Robien, Alicja Wolk, Roger L. Milne, Susanna C. Larsson, Melissa A. Merritt, Brian D. Carter, Sven Sandin, Julie R. Palmer, Alan A. Arslan, Leo J. Schouten, Shelley S. Tworoger, Michael Jones, Anne Zeleniuch-Jacquotte, Nicolas Wentzensen, Sarah R. Irvin, Hilde Langseth, Britton Trabert, I-Min Lee, Maria Elena Martinez, Graham G. Giles, Lynn Rosenberg, Victoria A. Kirsh, Julie E. Buring, Mary K. Townsend, Rudolf Kaaks, James V. Lacey, Jian-Min Yuan, Kala Visvanathan, Giske Ursin, Jenny N. Poynter, Synnove F. Knutsen, Thomas E. Rohan, Ulrike Peters, Renée T. Fortner, Elisabete Weiderpass, V. Wendy Setiawan, Anthony J. Swerdlow, Woon-Puay Koh, Piet A. van den Brandt, Dale P. Sandler, Epidemiologie, and RS: GROW - R1 - Prevention
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Ovarian Neoplasms ,Oncology ,RISK ,medicine.medical_specialty ,Epidemiology ,business.industry ,MORTALITY ,MEDLINE ,General Medicine ,Carcinoma, Ovarian Epithelial ,medicine.disease ,Cohort Studies ,Online Only ,Internal medicine ,Cohort ,Humans ,Medicine ,Female ,business ,Ovarian cancer ,POWDER - Published
- 2022
12. Data from microRNA Biomarker Discovery and High-Throughput DNA Sequencing Are Possible Using Long-term Archived Serum Samples
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Randi E. Gislefoss, Robert Lyle, Espen Enerly, Hilde Langseth, Marianne Lauritzen, and Trine B. Rounge
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Background: The impacts of long-term storage and varying preanalytical factors on the quality and quantity of DNA and miRNA from archived serum have not been fully assessed. Preanalytical and analytical variations and degradation may introduce bias in representation of DNA and miRNA and may result in loss or corruption of quantitative data.Methods: We have evaluated DNA and miRNA quantity, quality, and variability in samples stored up to 40 years using one of the oldest prospective serum collections in the world, the Janus Serumbank, a biorepository dedicated to cancer research.Results: miRNAs are present and stable in archived serum samples frozen at −25°C for at least 40 years. Long-time storage did not reduce miRNA yields; however, varying preanalytical conditions had a significant effect and should be taken into consideration during project design. Of note, 500 μL serum yielded sufficient miRNA for qPCR and small RNA sequencing and on average 650 unique miRNAs were detected in samples from presumably healthy donors. Of note, 500 μL serum yielded sufficient DNA for whole-genome sequencing and subsequent SNP calling, giving a uniform representation of the genomes.Conclusions: DNA and miRNA are stable during long-term storage, making large prospectively collected serum repositories an invaluable source for miRNA and DNA biomarker discovery.Impact: Large-scale biomarker studies with long follow-up time are possible utilizing biorepositories with archived serum and state-of-the-art technology. Cancer Epidemiol Biomarkers Prev; 24(9); 1381–7. ©2015 AACR.
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- 2023
13. Supplementary Tables 1-7 from Investigation of Established Genetic Risk Variants for Glioma in Prediagnostic Samples from a Population-Based Nested Case–Control Study
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Beatrice Melin, Ulrika Andersson, Tom Børge Johannesen, Preetha Rajaraman, Eivind Hovig, Hilde Langseth, Anna M. Dahlin, Florentin Späth, and Carl Wibom
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Supplementary Tables 1-7 Supplementary Table 1. PCR primers and conditions Supplementary Table 2. List of included diagnoses in each histological subgroup Supplementary Table 3. Associations between published genetic risk variants and risk of disease, calculated by conditional logistic regression; Glioma cases and matched controls Supplementary Table 4. Associations between published genetic risk variants and risk of disease, calculated by conditional logistic regression; GBM cases and matched controls Supplementary Table 5. Associations between published genetic risk variants and risk of disease, calculated by conditional logistic regression; Oligodendroglioma cases and matched controls Supplementary Table 6. Associations between published genetic risk variants and risk of disease, calculated by conditional logistic regression; Astrocytoma cases and matched controls Supplementary Table 7. Associations between published genetic risk variants and risk of disease, calculated by conditional logistic regression; Ependymoma cases and matched controls
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- 2023
14. Data from Investigation of Established Genetic Risk Variants for Glioma in Prediagnostic Samples from a Population-Based Nested Case–Control Study
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Beatrice Melin, Ulrika Andersson, Tom Børge Johannesen, Preetha Rajaraman, Eivind Hovig, Hilde Langseth, Anna M. Dahlin, Florentin Späth, and Carl Wibom
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Background: Although glioma etiology is poorly understood in general, growing evidence indicates a genetic component. Four large genome-wide association studies (GWAS) have linked common genetic variants with an increased glioma risk. However, to date, these studies are based largely on a case–control design, where cases have been recruited at the time of or after diagnosis. They may therefore suffer from a degree of survival bias, introduced when rapidly fatal cases are not included.Methods: To confirm glioma risk variants in a prospective setting, we have analyzed 11 previously identified risk variants in a set of prediagnostic serum samples with 598 cases and 595 matched controls. Serum samples were acquired from The Janus Serum Bank, a Norwegian population-based biobank reserved for cancer research.Results: We confirmed the association with glioma risk for variants within five genomic regions: 8q24.21 (CCDC26), 9p21.3 (CDKN2B-AS1), 11q23.3 (PHLDB1), 17p13.1 (TP53), and 20q13.33 (RTEL1). However, previously identified risk variants within the 7p11.2 (EGFR) region were not confirmed by this study.Conclusions: Our results indicate that the risk variants that were confirmed by this study are truly associated with glioma risk and may, consequently, affect gliomagenesis. Though the lack of positive confirmation of EGFR risk variants may be attributable to relatively limited statistical power, it nevertheless raises the question whether they truly are risk variants or markers for glioma prognosis.Impact: Our findings indicate the need for further studies to clarify the role of glioma risk loci with respect to prolonged survival versus etiology. Cancer Epidemiol Biomarkers Prev; 24(5); 810–6. ©2015 AACR.
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- 2023
15. Supplementary Material from microRNA Biomarker Discovery and High-Throughput DNA Sequencing Are Possible Using Long-term Archived Serum Samples
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Randi E. Gislefoss, Robert Lyle, Espen Enerly, Hilde Langseth, Marianne Lauritzen, and Trine B. Rounge
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Figure s1: Bioanalyzer trace, long RNA vs miRNA Figure s2: miRNA sequencing saturation curves Figure s3: Small RNA detected in Janus samples Table s1: Adjusted p-values for mean DNA yield between treatments. Significant values in bold. Figure s4: DNA yield by serum treatments Figure s5: Example of DNA Bioanalyzer trace Figure s6: DNA sequencing results Figure s7: Example of sequence distribution
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- 2023
16. Absolute Risk of Oropharyngeal Cancer After an HPV16-E6 Serology Test and Potential Implications for Screening: Results From the Human Papillomavirus Cancer Cohort Consortium
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Hilary A. Robbins, Aida Ferreiro-Iglesias, Tim Waterboer, Nicole Brenner, Mari Nygard, Noemi Bender, Lea Schroeder, Allan Hildesheim, Michael Pawlita, Gypsyamber D'Souza, Kala Visvanathan, Hilde Langseth, Nicolas F. Schlecht, Lesley F. Tinker, Ilir Agalliu, Sylvia Wassertheil-Smoller, Eivind Ness-Jensen, Kristian Hveem, Sara Grioni, Rudolf Kaaks, Maria-Jose Sánchez, Elisabete Weiderpass, Graham G. Giles, Roger L. Milne, Qiuyin Cai, William J. Blot, Wei Zheng, Stephanie J. Weinstein, Demetrius Albanes, Wen-Yi Huang, Neal D. Freedman, Aimée R. Kreimer, Mattias Johansson, and Paul Brennan
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Male ,Cancer Research ,Human papillomavirus 16 ,Papillomavirus Infections ,Oncogene Proteins, Viral ,Middle Aged ,Alphapapillomavirus ,Antibodies, Viral ,Oropharyngeal Neoplasms ,Oncology ,Humans ,Female ,Papillomaviridae ,Early Detection of Cancer - Abstract
PURPOSE Seropositivity for the HPV16-E6 oncoprotein is a promising marker for early detection of oropharyngeal cancer (OPC), but the absolute risk of OPC after a positive or negative test is unknown. METHODS We constructed an OPC risk prediction model that integrates (1) relative odds of OPC for HPV16-E6 serostatus and cigarette smoking from the human papillomavirus (HPV) Cancer Cohort Consortium (HPVC3), (2) US population risk factor data from the National Health Interview Survey, and (3) US sex-specific population rates of OPC and mortality. RESULTS The nine HPVC3 cohorts included 365 participants with OPC with up to 10 years between blood draw and diagnosis and 5,794 controls. The estimated 10-year OPC risk for HPV16-E6 seropositive males at age 50 years was 17.4% (95% CI, 12.4 to 28.6) and at age 60 years was 27.1% (95% CI, 19.2 to 45.4). Corresponding 5-year risk estimates were 7.3% and 14.4%, respectively. For HPV16-E6 seropositive females, 10- year risk estimates were 3.6% (95% CI, 2.5 to 5.9) at age 50 years and 5.5% (95% CI, 3.8 to 9.2) at age 60 years and 5-year risk estimates were 1.5% and 2.7%, respectively. Over 30 years, after a seropositive result at age 50 years, an estimated 49.9% of males and 13.3% of females would develop OPC. By contrast, 10-year risks among HPV16-E6 seronegative people were very low, ranging from 0.01% to 0.25% depending on age, sex, and smoking status. CONCLUSION We estimate that a substantial proportion of HPV16-E6 seropositive individuals will develop OPC, with 10-year risks of 17%-27% for males and 4%-6% for females age 50-60 years in the United States. This high level of risk may warrant periodic, minimally invasive surveillance after a positive HPV16-E6 serology test, particularly for males in high-incidence regions. However, an appropriate clinical protocol for surveillance remains to be established., United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) 5U01CA195603-02 U01CA202979, Division of Cancer Epidemiology and Genetics, US NCI, VicHealth, Canadian Institutes of Health Research (CIHR), Cancer Council Victoria, National Health and Medical Research Council (NHMRC) of Australia 209057 396414 1074383, National Cancer Institute P30 CA016056, Einstein Cancer Research Center CA013330, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA, NIH National Heart Lung & Blood Institute (NHLBI) 75N92021D00001 75N92021D00002 75N92021D00003 75N92021D00004 75N92021D00005
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- 2022
17. A 10-year prediagnostic follow-up study shows that serum RNA signals are highly dynamic in lung carcinogenesis
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Åslaug Helland, Trine B. Rounge, Robert Lyle, Andreas Keller, Hilde Langseth, Sinan Uğur Umu, and Eckart Meese
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,Lung Neoplasms ,Time Factors ,Carcinogenesis ,RNA-Seq ,medicine.disease_cause ,NSCLC ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Stage (cooking) ,Biomarker discovery ,prediagnostic serum ,Research Articles ,SCLC ,General Medicine ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Molecular Medicine ,Blood Banks ,RNA‐seq ,Female ,Cell-Free Nucleic Acids ,Research Article ,Adult ,medicine.medical_specialty ,Biology ,lcsh:RC254-282 ,03 medical and health sciences ,Internal medicine ,Genetics ,medicine ,Biomarkers, Tumor ,Humans ,Lung cancer ,RNA ,Cancer ,Histology ,medicine.disease ,lung cancer ,030104 developmental biology ,Case-Control Studies ,RNA, Small Untranslated ,RNA dynamics ,RNA-seq ,Follow-Up Studies - Abstract
The majority of lung cancer (LC) patients are diagnosed at a late stage, and survival is poor. Circulating RNA molecules are known to have a role in cancer; however, their involvement before diagnosis remains an open question. In this study, we investigated circulating RNA dynamics in prediagnostic LC samples, focusing on smokers, to identify if and when disease‐related signals can be detected in serum. We sequenced small RNAs in 542 serum LC samples donated up to 10 years before diagnosis and 519 matched cancer‐free controls coming from 905 individuals in the Janus Serum Bank. This sample size provided sufficient statistical power to independently analyze time to diagnosis, stage, and histology. The results showed dynamic changes in differentially expressed circulating RNAs specific to LC histology and stage. The greatest number of differentially expressed RNAs was identified around 7 years before diagnosis for early‐stage LC and 1–4 years prior to diagnosis for locally advanced and advanced‐stage LC, regardless of LC histology. Furthermore, NSCLC and SCLC histologies have distinct prediagnostic signals. The majority of differentially expressed RNAs were associated with cancer‐related pathways. The dynamic RNA signals pinpointed different phases of tumor development over time. Stage‐specific RNA profiles may be associated with tumor aggressiveness. Our results improve the molecular understanding of carcinogenesis. They indicate substantial opportunity for screening and improved treatment and will guide further research on early detection of LC. However, the dynamic nature of the RNA signals also suggests challenges for prediagnostic biomarker discovery., We investigated circulating RNA dynamics in prediagnostic lung cancer (LC) samples, focusing on smokers, to identify if and when disease‐related signals can be detected in serum. The results showed dynamic changes in differentially expressed circulating RNAs specific to LC histology and stage. The dynamic RNA signals identified different phases of tumor development over time and were associated with cancer‐related pathways.
- Published
- 2022
- Full Text
- View/download PDF
18. Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia
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Eleanor L, Watts, Aurora, Perez-Cornago, Georgina K, Fensom, Karl, Smith-Byrne, Urwah, Noor, Colm D, Andrews, Marc J, Gunter, Michael V, Holmes, Richard M, Martin, Konstantinos K, Tsilidis, Demetrius, Albanes, Aurelio, Barricarte, Bas, Bueno-de-Mesquita, Chu, Chen, Barbara A, Cohn, Niki L, Dimou, Luigi, Ferrucci, Leon, Flicker, Neal D, Freedman, Graham G, Giles, Edward L, Giovannucci, Gary E, Goodman, Christopher A, Haiman, Graeme J, Hankey, Jiaqi, Huang, Wen-Yi, Huang, Lauren M, Hurwitz, Rudolf, Kaaks, Paul, Knekt, Tatsuhiko, Kubo, Hilde, Langseth, Gail, Laughlin, Loic, Le Marchand, Tapio, Luostarinen, Robert J, MacInnis, Hanna O, Mäenpää, Satu, Männistö, E Jeffrey, Metter, Kazuya, Mikami, Lorelei A, Mucci, Anja W, Olsen, Kotaro, Ozasa, Domenico, Palli, Kathryn L, Penney, Elizabeth A, Platz, Harri, Rissanen, Norie, Sawada, Jeannette M, Schenk, Pär, Stattin, Akiko, Tamakoshi, Elin, Thysell, Chiaojung Jillian, Tsai, Shoichiro, Tsugane, Lars, Vatten, Elisabete, Weiderpass, Stephanie J, Weinstein, Lynne R, Wilkens, Bu B, Yeap, Naomi E, Allen, Timothy J, Key, Ruth C, Travis, Department of Public Health, HUS Comprehensive Cancer Center, and Department of Oncology
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Male ,Cancer Research ,CALCULATED FREE TESTOSTERONE ,3122 Cancers ,Prostatic Neoplasms/epidemiology ,PSA ,Risk Factors ,Sex Hormone-Binding Globulin ,BINDING ,Sex Hormone-Binding Globulin/analysis ,Humans ,Testosterone ,SHBG ,Mendelian randomisation ,Cancer och onkologi ,FOCUS ,Prostate ,Prostatic Neoplasms ,MEN ,Mendelian Randomization Analysis ,prostate cancer ,Oncology ,aggressive prostate cancer ,Cancer and Oncology ,testosterone ,FINASTERIDE ,ICEP ,SENSITIVITY ,FOLLOW-UP ,Biomarkers - Abstract
Publisher Copyright: © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged
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- 2022
19. Prediagnostic circulating levels of sex hormones and survival in esophageal adenocarcinoma
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Jesper Lagergren, Eivind Ness-Jensen, Hilde Langseth, Shao-Hua Xie, Randi Elin Gislefoss, and Fredrik Mattsson
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Adult ,Male ,gonadal steroid hormones ,Cancer Research ,Esophageal Neoplasms ,Population ,Physiology ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Dehydroepiandrosterone sulfate ,Sex hormone-binding globulin ,Sex Hormone-Binding Globulin ,Humans ,Medicine ,education ,Testosterone ,Aged ,education.field_of_study ,adenocarcinoma ,biology ,business.industry ,Hazard ratio ,Middle Aged ,Survival Analysis ,mortality ,Prolactin ,Survival Rate ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Multivariate Analysis ,biology.protein ,prognosis ,Follicle Stimulating Hormone ,Luteinizing hormone ,business ,Body mass index ,Cancer Epidemiology - Abstract
Sex hormonal differences may contribute to the strong male predominance in esophageal adenocarcinoma (EAC), but whether sex hormone levels influence survival in EAC is unstudied. Our study aimed to assess associations between prediagnostic sex hormone levels and survival in EAC. In a population‐based cohort study, 244 male EAC patients from the Janus Serum Bank Cohort in Norway were followed up through 2018. Associations between prediagnostic serum levels of 12 sex hormone measures and disease‐specific mortality were assessed using multivariable Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, body mass index, tobacco smoking, physical activity and surgical resection. Higher levels of sex hormone‐binding globulin (SHBG) indicated decreased disease‐specific mortality (HR 0.68, 95% CI 0.44‐1.07, highest vs lowest tertile). In stratified analyses by surgery, such associations remained in nonoperated patients (HR 0.58, 95% CI 0.35‐0.96, highest vs lowest tertile), but not in operated patients. Higher levels of follicle‐stimulating hormone (FSH) were associated with increased disease‐specific mortality in an exposure‐response pattern; HRs for the middle and highest tertiles vs the lowest tertile were 1.35 (95% CI 0.89‐2.05) and 1.61 (95% CI 1.06‐2.43), respectively. No clear associations were observed with serum levels of dehydroepiandrosterone sulfate, luteinizing hormone, prolactin, testosterone, 17‐OH‐progesterone, progesterone, estradiol, androstenedione, testosterone:estradiol ratio or free testosterone index. These findings suggest that higher endogenous levels of SHBG and lower levels of FSH may increase the survival in EAC. The other 10 examined sex hormone measures may not influence the survival., What's new? Esophageal adenocarcinoma (EAC) occurs more frequently in men than women. Whether this pattern is linked to differences in sex hormone levels and whether such differences impact EAC survival remain unclear. In this study of male EAC patients in Norway, analyses of prediagnostic sex hormone measures uncovered associations between reduced disease‐specific mortality and increased sex hormone‐binding globulin and decreased follicle‐stimulating hormone levels. The associations were detected only in patients who had not undergone surgery. Ten other sex hormone measures also analyzed had no influence on survival. Additional investigation is needed to better understand relationships between sex hormone levels and EAC survival.
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- 2020
20. Circulating Sex Hormone Levels and Risk of Esophageal Adenocarcinoma in a Prospective Study in Men
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Shao-Hua Xie, Fredrik Mattsson, Hilde Langseth, Randi Elin Gislefoss, Sirus Rabbani, Jesper Lagergren, and Eivind Ness-Jensen
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Hepatology ,biology ,business.industry ,Gastroenterology ,Case-control study ,Physiology ,Odds ratio ,Prolactin ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Dehydroepiandrosterone sulfate ,Sex hormone-binding globulin ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Medicine ,030211 gastroenterology & hepatology ,Prospective cohort study ,business ,Luteinizing hormone ,Testosterone - Abstract
Objectives Sex hormones have been hypothesized to explain the strong male predominance in esophageal adenocarcinoma, but evidence is needed. This study examined how circulating sex hormone levels influence future risk of esophageal adenocarcinoma. Methods This case-control study was nested in a prospective Norwegian cohort (Janus Serum Bank Cohort), including 244 male patients with esophageal adenocarcinoma and 244 male age-matched control participants. Associations between prediagnostic circulating levels of 12 sex hormones and risk of esophageal adenocarcinoma were assessed using conditional logistic regression. In addition, a random-effect meta-analysis combined these data with a similar prospective study for 5 sex hormones. Results Decreased odds ratios (ORs) of esophageal adenocarcinoma were found comparing the highest with lowest quartiles of testosterone (OR = 0.44, 95% confidence interval [CI] 0.22-0.88), testosterone:estradiol ratio (OR = 0.37, 95% CI 0.19-0.72), and luteinizing hormone (OR = 0.50, 95% CI 0.30-0.98), after adjustment for tobacco smoking and physical activity. These associations were attenuated after further adjustment for body mass index (OR = 0.56, 95% CI 0.27-1.13 for testosterone; OR = 0.46, 95% CI 0.23-0.91 for testosterone:estradiol ratio; OR = 0.55, 95% CI 0.29-1.08 for luteinizing hormone). No associations were observed for sex hormone-binding globulin, dehydroepiandrosterone sulfate, follicle-stimulating hormone, prolactin, 17-OH progesterone, progesterone, androstenedione, or free testosterone index. The meta-analysis showed an inverse association between testosterone levels and risk of esophageal adenocarcinoma (pooled OR for the highest vs lowest quartile = 0.60, 95% CI 0.38-0.97), whereas no associations were identified for androstenedione, sex hormone-binding globulin, estradiol, or testosterone:estradiol ratio. Discussion Higher circulating testosterone levels may decrease the risk of esophageal adenocarcinoma in men.
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- 2019
21. Prediagnostic serum sCD27 and sCD30 in serial samples and risks of non‐Hodgkin lymphoma subtypes
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Nathaniel Rothman, Qing Lan, Mark P. Purdue, Tom Kristian Grimsrud, Hilde Langseth, and Allan Hildesheim
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Chronic lymphocytic leukemia ,Follicular lymphoma ,Ki-1 Antigen ,Single sample ,Risk Assessment ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Biomarkers, Tumor ,Odds Ratio ,medicine ,Humans ,Longitudinal Studies ,Lymphoma, Follicular ,Aged ,Aged, 80 and over ,Norway ,business.industry ,Odds ratio ,Middle Aged ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Confidence interval ,Tumor Necrosis Factor Receptor Superfamily, Member 7 ,Lymphoma ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Hodgkin lymphoma ,Female ,Multiple Myeloma ,business ,Cohort study - Abstract
Elevated pre-diagnostic serum levels of the immune activation markers sCD27 and sCD30 have been associated with non-Hodgkin lymphoma (NHL). However, the use of a single sample per participant in these studies has limited etiologic inferences. We report findings, overall and by NHL subtype, from a case-control analysis (422 cases, 434 controls) within the Janus Serum Bank with two samples per subject collected on average five years apart. Chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL) was associated with elevated sCD27 in the later, but not earlier, pre-diagnostic sample (odds ratio [OR] 4.2, 95% confidence interval [CI] 1.5-11.6 and 1.7, 0.7-4.7 per log increase respectively) in analyses adjusting for both analytes, while follicular lymphoma (FL) was associated with elevated sCD30 in both the later and earlier samples (OR 2.9, 95% CI 1.4-4.4 and 2.3, 1.2-4.4 respectively). CLL/SLL cases were significantly more likely than controls to have higher sCD27 in the later vs. earlier sample (OR 1.4, 95% CI 1.1-1.9 per standard deviation increase); no such difference in sCD30 was apparent for FL. In a joint analysis, NHL cases were more likely than controls to have below-median sCD27 in the earlier sample and above-median sCD27 in the later sample (OR 1.5, 95% CI 1.0-2.3). For sCD30, the association between sCD30 and FL was confined to subjects with above-median analyte levels in both samples (OR 2.5, 95% CI 1.1-5.9). Our findings are compatible with elevated sCD27 representing a disease-induced effect and sCD30 representing a marker of increased FL susceptibility.
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- 2019
22. Author response: Serum RNAs can predict lung cancer up to 10 years prior to diagnosis
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Sinan U Umu, Hilde Langseth, Verena Zuber, Åslaug Helland, Robert Lyle, and Trine B Rounge
- Published
- 2021
23. Prediagnostic Serum-25 Hydroxyvitamin D and Mortality Among Bladder Cancer Patients in the Janus Serum Bank Cohort: Answer to a Short Comment [Response to Letter]
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Karol Axcrona, Helga H Hektoen, Bettina Kulle Andreassen, Trude Eid Robsahm, Jo S Stenehjem, and Hilde Langseth
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Oncology ,medicine.medical_specialty ,Bladder cancer ,Letter ,Epidemiology ,business.industry ,MEDLINE ,medicine.disease ,Internal medicine ,Cohort ,medicine ,Clinical Epidemiology ,Serum 25 hydroxyvitamin d ,business - Abstract
Bettina K Andreassen,1 Helga H Hektoen,1 Karol Axcrona,2 Hilde Langseth,1 Jo S Stenehjem,1 Trude E Robsahm1 1Department of Research, Cancer Registry of Norway, Oslo, Norway; 2Department of Urology, Akershus University Hospital, Lørenskog, NorwayCorrespondence: Helga H Hektoen Email Helga.Helseth.Hektoen@kreftregisteret.no View the original paper by Dr Hektoen and colleagues This is in response to the Letter to the Editor
- Published
- 2021
24. A Simple and Cost-Effective Method for Measuring Hemolysis in Biobank Serum Specimens
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Hilde Langseth, Randi Elin Gislefoss, Urszula Berge, Marcin W. Wojewodzic, and Marianne Lauritzen
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Chromatography ,Wilcoxon signed-rank test ,Chemistry ,Sample (material) ,Cost-Benefit Analysis ,Medicine (miscellaneous) ,Centrifugation ,Cell Biology ,General Medicine ,medicine.disease ,Serum samples ,Hemolysis ,General Biochemistry, Genetics and Molecular Biology ,Freezing ,medicine ,Humans ,Statistical analysis ,Hemoglobin ,Turbidity ,Biological Specimen Banks - Abstract
Background: During sampling and processing, blood samples can be affected by hemolysis. Information is lacking regarding hemolysis for biobank samples. There is a need for a method that can easily measure hemoglobin as an indicator of hemolysis in stored samples before they are included in research projects. In this study we present a simple method for estimating hemolysis and investigate the effect of centrifugation speeds and temperatures on sample turbidity that commonly interferes with measurements. Methods: Using a variation of the Beer-Lambert law, we quantified the hemoglobin concentration in 75 long-term stored samples at a wavelength of 414 nm with a NanoDrop™ 8000 spectrophotometer. Owing to interference from turbidity, the samples underwent different treatments post-thawing: centrifugation at 10,000 and 20,000 g at two different temperatures (4°C and 19°C) for 15 minutes. In addition, freshly collected serum samples (n = 20) underwent a single freeze-thaw cycle, with hemoglobin measured prefreeze, post-thaw, and postcentrifugation. Kruskal-Wallis rank sum test groups and pairwise Wilcoxon rank test were used for statistical analysis. Results: A strong effect of centrifugation on the turbidity was shown for the long-term stored samples, however, this effect was independent of the temperature or centrifugation speeds. Centrifugation at 20,000 g for 15 minutes at 19°C reduced the turbidity up to 50%. A single freeze-thaw cycle in the fresh samples increased the optical density at 414 nm slightly, indicating a false increase of hemoglobin concentration. The following centrifugation reduced the concentration to less than the initial sample measurements, suggesting the presence of interference immediately after sampling. Conclusion: We describe here a simple and cost-effective NanoDrop-based method for measuring hemolysis levels intended for use in biobank facilities. We found that centrifugation, but not temperature, is a crucial step to reduce interference from turbidity.
- Published
- 2021
25. Prediagnostic blood levels of organochlorines and risk of non‐Hodgkin lymphoma in three prospective cohorts in China and Singapore
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Mark P. Purdue, Dazhe Chen, Jason Y.Y. Wong, Xiao-Ou Shu, Andreas Sjödin, Bryan A. Bassig, Yong-Bing Xiang, Jian-Min Yuan, Lawrence S. Engel, Yu-Tang Gao, Renwei Wang, Richard S. Jones, Jennifer M. Adams-Haduch, Hilde Langseth, Wei Hu, Woon-Puay Koh, Bu Tian Ji, Tom Kristian Grimsrud, Wei Zheng, Gong Yang, Qing Lan, Wei Jie Seow, Nathaniel Rothman, Mark D. Davis, and H. Dean Hosgood
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Male ,China ,Cancer Research ,Physiology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Hydrocarbons, Chlorinated ,medicine ,Humans ,Prospective Studies ,Pesticides ,Aged ,Singapore ,business.industry ,Lymphoma, Non-Hodgkin ,Polychlorinated biphenyl ,Blood collection ,Middle Aged ,Pesticide ,medicine.disease ,Lymphoma ,Increased risk ,Oncology ,Dichlorodiphenyldichloroethylene ,chemistry ,Case-Control Studies ,030220 oncology & carcinogenesis ,Hodgkin lymphoma ,Environmental Pollutants ,Female ,Conditional logistic regression ,business ,Follow-Up Studies - Abstract
Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g. dichlorodiphenyltrichloroethane (DDT), hexachlorocyclohexane (HCH)) are different from Western populations. We evaluated NHL risk and pre-diagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl (PCB) congeners in a case-control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE), the primary DDT metabolite, and β-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher β-HCH levels both overall (3(rd) vs. 1(st) tertile OR=1.8, 95%CI=1.0-3.2; p(trend) =0.049) and after excluding cases diagnosed within two years of blood collection (3(rd) vs. 1(st) tertile OR = 2.0, 95%CI =1.1-3.9; p(trend) = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p’-DDE. Our findings provide support for an association between β-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p’-DDE do not support an association.
- Published
- 2019
26. Pre-diagnostic serum concentrations of organochlorines and risk of acute myeloid leukemia: A nested case-control study in the Norwegian Janus Serum Bank Cohort
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Aaron Blair, Mark P. Purdue, Lawrence S. Engel, Roel Vermeulen, Kenneth P. Cantor, Dana B. Barr, Tom Kristian Grimsrud, Hilde Langseth, Jason Y.Y. Wong, Bryan A. Bassig, Nathaniel Rothman, and Qing Lan
- Subjects
Adult ,Male ,010504 meteorology & atmospheric sciences ,Heptachlor ,Heptachlor Epoxide ,Population ,Physiology ,Chlordane ,010501 environmental sciences ,Risk Assessment ,01 natural sciences ,DDT ,Cohort Studies ,Young Adult ,chemistry.chemical_compound ,Hydrocarbons, Chlorinated ,Odds Ratio ,Humans ,Medicine ,Pesticides ,education ,lcsh:Environmental sciences ,0105 earth and related environmental sciences ,General Environmental Science ,lcsh:GE1-350 ,education.field_of_study ,Acute leukemia ,Norway ,business.industry ,Odds ratio ,Middle Aged ,Polychlorinated Biphenyls ,Leukemia, Myeloid, Acute ,Logistic Models ,chemistry ,Chlordan ,Case-Control Studies ,Nested case-control study ,Cohort ,Environmental Pollutants ,Female ,business - Abstract
Background: Epidemiologic studies suggest an increased risk of leukemia among individuals occupationally exposed to some organochlorine (OC) compounds. Associations between serum OC pesticide and polychlorinated biphenyl (PCB) levels and risk of acute myeloid leukemia (AML), the most common subtype of acute leukemia in adult populations, have not been evaluated prospectively in the general population. Objective: We evaluated the risk of AML in relation to pre-diagnostic serum levels of OC pesticides and PCBs in a case-control study nested within the Janus Serum Bank Cohort. Methods: Janus is a large population-based cohort containing biologic samples collected beginning in the early 1970s from ~318,000 individuals in Norway. Serum levels of 11 OC pesticides or their metabolites and 34 PCB congeners were measured in 56 AML cases and 288 controls. Conditional logistic regression was conducted to evaluate associations between lipid-adjusted serum OC levels and risk of AML. Results: Higher serum levels of total chlordane/heptachlor metabolites were associated with AML risk (3rd vs. 1st tertile odds ratio (OR) = 2.26, 95% confidence interval (CI) = 0.91–5.63; ptrend = 0.11). Significant exposure-response associations were observed for levels of heptachlor epoxide (3rd vs. 1st tertile OR = 2.85, 95% CI = 1.05–7.73; ptrend = 0.02) and dieldrin (3rd vs. 1st tertile OR = 2.71, 95% CI = 1.07–6.83; ptrend = 0.03). No significant exposure-response associations with AML risk were observed for total DDT or individual isomers and derivatives. Higher serum levels of p,p′-DDT showed a non-significant increase in risk, but the exposure-response became attenuated when co-adjusting for heptachlor epoxide or dieldrin levels. Serum PCB levels were not significantly associated with AML risk. Conclusions: Our data suggest that higher serum levels of dieldrin and metabolites derived from chlordane/heptachlor are associated with risk of AML in the general Norwegian population, based on samples collected on average ~17 years before diagnosis. Further research in populations with historically high or recent exposure to DDT is warranted to assess the association with AML risk with body burden of specific DDT isomers and derivatives. Keywords: Acute myeloid leukemia, Organochlorines, Pesticides, Polychlorinated biphenyls
- Published
- 2019
27. Nasopharyngeal carcinoma patients from Norway show elevated Epstein-Barr virus IgA and IgG antibodies prior to diagnosis
- Author
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Julia Simon, Nicole Brenner, Sibylle Reich, Hilde Langseth, Bo T. Hansen, Giske Ursin, Aida Ferreiro-Iglesias, Paul Brennan, Aimée R. Kreimer, Mattias Johansson, Miranda Pring, Mari Nygard, and Tim Waterboer
- Subjects
Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Cancer Research ,Nasopharyngeal Carcinoma ,Epidemiology ,Papillomavirus Infections ,Nasopharyngeal Neoplasms ,Nested case/control study ,Antibodies, Viral ,Immunoglobulin A ,Oncology ,Immunoglobulin G ,Nasopharyngeal carcinoma ,Epstein-Barr virus ,Humans ,RNA ,Prospective Studies ,Multiplex serology ,Biomarkers ,Prospective biomarker - Abstract
BackgroundIgA antibodies against few Epstein-Barr virus (EBV) proteins are established serological markers for nasopharyngeal carcinoma (NPC). We recently validated a novel, comprehensive EBV marker panel and showed that IgA, but also IgG antibodies against multiple EBV proteins are highly sensitive and specific for EBV-positive NPC at diagnosis. However, data about these novel biomarkers as prospective markers for NPC are sparse.MethodsThis study included 30 incident NPC cases and 60 matched controls from the Norwegian Janus Serum Bank. For 21 NPCs, molecular EBV and human papillomavirus (HPV) status were assessed by EBER-ISH and HPV DNA/RNA testing by PCR, respectively. IgA and IgG serum antibodies against 17 EBV antigens were analyzed in prediagnostic sera of cases (median lead time 14 years) and controls using multiplex serology. Sensitivities were calculated using receiver operating characteristic analysis pre-specified to yield 90% specificity in the control group. From 10 cases, serial samples were available.ResultsQuantitative EBV antibody levels were significantly elevated among all cases (p ConclusionBoth, EBV IgA and IgG antibody levels are significantly elevated many years before diagnosis of EBV-positive NPCs in Norway, an NPC low-incidence region. This study provides insights into one of the largest available prospective sample collections of NPCs in a non-endemic country.
- Published
- 2022
28. Data Resource Profile: thousands of circulating RNA profiles of pre-clinical samples from the Janus Serum Bank Cohort
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Trine B. Rounge, Hilde Langseth, Magnus Leithaug, Cecilie Bucher-Johannessen, Robert Lyle, Sinan Uğur Umu, Paolo Vineis, Marianne Lauritzen, Giske Ursin, and Babigumira R
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Oncology ,medicine.medical_specialty ,business.industry ,Rectum ,Cancer ,RNA ,Anthropometry ,medicine.disease ,medicine.disease_cause ,Cancer registry ,medicine.anatomical_structure ,Internal medicine ,Cohort ,microRNA ,Medicine ,business ,Carcinogenesis - Abstract
There is justified optimism regarding the use of miRNAs as early detection biomarkers of cancer. They are well characterized and are involved in all the hallmarks of cancer. Less is known about the role of most other non-coding RNA (ncRNAs) classes in normal physiology and tumorigenesis. The JanusRNA dataset consist of circulating RNA profiles of pre-clinical samples from 1631 cancer patients and 673 cancer-free controls. We studied eight cancer types including cancer of the: lung, colon, rectum, prostate, breast, testis, ovaries and gallbladder. JanusRNA has its origin from the large population-based Janus Serum Bank Cohort which consists of 318 628 Norwegians. The dataset combines information from the complete nationwide cancer registry, RNA sequencing profiles from 1631 cancer patients and 673 cancer-free controls, as well as data on lifestyle, anthropometry and biochemical measurements from national health surveys. The Janus Serum Bank is specifically suited for studies of early detection and risk biomarkers of cancer, since samples are collected nationwide over a large time span, pre-clinically and cancer occurs at different points in time after blood draw. We used a nested case-control design, selecting both cases and controls among the Janus cohort members. We restricted our selection to cases with at least one sample collected within 10 years prior to cancer diagnosis. We selected 673 cancer-free Janus participants for comparison of RNA levels with the cancer cases. The controls were frequency matched to the case group on sex, age at blood donation and date of blood donation. The JanusRNA dataset has been used to investigate the natural variation of circulating RNAs in cancer-free individuals. This data resource was also used in a study of variation in RNA expression associated with common traits like age, sex, smoking, BMI and physical activity in cancer-free individuals. RNA dynamics in lung and testicular carcinogenesis throughout a 10-year follow-up has also been studied.
- Published
- 2021
29. Recommended Definitions of Aggressive Prostate Cancer for Etiologic Epidemiologic Research
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Stella Koutros, Graham G. Giles, Sonja I. Berndt, Jiaqi Huang, Sherly X. Li, Sarah C. Markt, Elizabeth A. Platz, Timothy J. Key, Corinne E. Joshu, Eric J. Jacobs, Wu Lang, Chu Chen, Thomas E. Rohan, Stephanie J. Weinstein, Qiuyin Cai, Ruth C. Travis, Konrad H. Stopsack, Michael B. Cook, Lorelei A. Mucci, Hilde Langseth, Synnove F. Knutsen, Jeanine M. Genkinger, Ilir Agalliu, Kathryn Hughes Barry, Kathryn L. Penney, Demetrius Albanes, Robert J. MacInnis, Meir J. Stampfer, Aurora Perez-Cornago, Stephanie A. Smith-Warner, Catherine M. Tangen, Lauren M. Hurwitz, and Iona Cheng
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Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Population ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Predictive Value of Tests ,Internal medicine ,Epidemiology ,Humans ,Medicine ,Epidemiologic research ,education ,Neoplasm Staging ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Errata ,business.industry ,Prostate ,Prostatic Neoplasms ,Cancer ,Articles ,Prostate-Specific Antigen ,medicine.disease ,Confidence interval ,Prostate-specific antigen ,030220 oncology & carcinogenesis ,Etiology ,Neoplasm Grading ,business - Abstract
Background In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research. Methods Among prostate cancer cases diagnosed in 2007 in the National Cancer Institute’s Surveillance, Epidemiology, and End Results-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV). Results In our case population (n = 55 900), 3073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM staging and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of category T4 or N1 or M1 or Gleason score of 8 or greater prostate cancer, because this definition had one of the higher PPVs (0.23, 95% confidence interval = 0.22 to 0.24) and reasonable sensitivity (0.66, 95% confidence interval = 0.64 to 0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses. Conclusions We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced category (T4 or N1 or M1), high-grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.
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- 2020
30. Competitive learning suggests circulating miRNA profiles for cancers decades prior to diagnosis
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Trine B. Rounge, Fabian Kern, Andreas Keller, Eckart Meese, Tobias Fehlmann, Nicole Ludwig, Christina Backes, Hilde Langseth, and Randi Elin Gislefoss
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Oncology ,medicine.medical_specialty ,Colorectal cancer ,Population ,Biology ,Bioinformatics ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Artificial Intelligence ,Neoplasms ,Internal medicine ,microRNA ,Biomarkers, Tumor ,Humans ,Medicine ,Circulating MicroRNA ,Liquid biopsy ,Lung cancer ,education ,Molecular Biology ,Gene ,Early Detection of Cancer ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Lung ,business.industry ,Liquid Biopsy ,Computational Biology ,Cancer ,Cell Biology ,Non-coding RNA ,medicine.disease ,MicroRNAs ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Analysis of variance ,business ,Research Paper ,Blood drawing - Abstract
Small non-coding RNAs such as microRNAs are master regulators of gene expression. One of the most promising applications of miRNAs is the use as liquid biopsy. Especially early diagnosis is an effective means to increase patients’ overall survival. E.g. in oncology a tumor is detected at best prior to its clinical manifestation. We generated genome-wide miRNA profiles from serum of patients and controls from the population-based Janus Serum Bank (JSB) and analyzed them by bioinformatics and artificial intelligence approaches. JSB contains sera from 318,628 originally healthy persons, more than 96,000 of whom later developed cancer. We selected 210 serum samples of patients with lung, colon or breast cancer at three time points prior to diagnosis, after cancer diagnosis and controls. The controls were matched with regard to age of the blood donor and to the time points of blood drawing, which were 27, 32, or 38 years prior to diagnosis. Using ANOVA we report 70 significantly deregulated markers (adjusted p-value−10). Further, 91miRNAs were differently expressed in pre-diagnostic samples as compared to controls (nominal p
- Published
- 2020
31. Circulating isoflavone and lignan concentrations and prostate cancer risk: a meta-analysis of individual participant data from seven prospective studies including 2,828 cases and 5,593 controls
- Author
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Emily Sonestedt, Peter Wallström, Konstantinos K. Tsilidis, Isabel Drake, Shoichiro Tsugane, Pär Stattin, Kazuya Mikami, Robert Luben, Antonia Trichopoulou, Aurora Perez-Cornago, Paul N. Appleby, Norie Sawada, Tatsuhiko Kubo, Ruth C. Travis, Fulvio Ricceri, Leire Gil, Anders Johansson, Rikard Landberg, Cecilie Kyrø, Akiko Tamakoshi, Hilde Langseth, Neil Murphy, Randi Elin Gislefoss, Naomi E. Allen, Heiner Boeing, Lena Maria Nilsson, Kay-Tee Khaw, Kotaro Ozasa, and Timothy J. Key
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,030109 nutrition & dietetics ,business.industry ,Daidzein ,food and beverages ,Genistein ,Equol ,Lower risk ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,chemistry ,Enterolactone ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Phytoestrogens ,Enterodiol ,business - Abstract
Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between prediagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs. Q1 = 0.61, 95% confidence interval [CI] = 0.39–0.97), although there was no significant trend (OR per 75 percentile increase = 0.69, 95 CI = 0.46–1.05, ptrend = 0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs. Q1 = 0.70, 0.45–1.10 and 0.71, 0.45–1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that prediagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high.
- Published
- 2018
32. Prediagnostic serum concentrations of organochlorine pesticides and non-Hodgkin lymphoma: A nested case-control study in the Norwegian Janus Serum Bank Cohort
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Qing Lan, Lawrence S. Engel, Tom Kristian Grimsrud, Bryan A. Bassig, Nathaniel Rothman, Kenneth P. Cantor, Dazhe Chen, Dana B. Barr, Hilde Langseth, Marilie D. Gammon, and Aaron Blair
- Subjects
medicine.medical_specialty ,Population ,010501 environmental sciences ,01 natural sciences ,Biochemistry ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Epidemiology ,Hydrocarbons, Chlorinated ,Medicine ,Humans ,030212 general & internal medicine ,Pesticides ,education ,0105 earth and related environmental sciences ,General Environmental Science ,education.field_of_study ,business.industry ,Norway ,Incidence (epidemiology) ,Lymphoma, Non-Hodgkin ,Odds ratio ,Confidence interval ,Quartile ,Case-Control Studies ,Nested case-control study ,Cohort ,business - Abstract
Background Much of the marked increase in incidence of non-Hodgkin lymphoma (NHL) over the past few decades remains unexplained. Organochlorines, including organochlorine pesticides (OCPs), have been implicated as possible contributors to the increase, but the evidence is inconsistent. Objectives To investigate the relation between pre-diagnostic levels of OCPs and risk of NHL in a case-control study nested within the population-based Janus Serum Bank Cohort in Norway. Methods Prediagnostic concentrations of 11 OCPs or OCP metabolites were measured in baseline blood samples collected between 1972 and 1978 from 190 cases and 190 controls matched on sex, county, age at blood draw, and date of blood draw. We conducted conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for each quartile of lipid-corrected OCP/metabolite relative to the lowest quartile. Results We observed non-significantly elevated ORs across quartiles of β-hexachlorocyclohexane compared to the lowest quartile (OR range: 1.40–1.82) although with no apparent monotonic exposure-response relationship. We also found an inverse association between risk of NHL and o,p'-DDT (OR for Q4 vs. Q1 = 0.44, 95% CI: 0.19, 1.01; p-trend = 0.05). In analyses stratified by age at blood collection and duration of follow-up, several other analytes, primarily chlordane-related compounds, showed inverse associations among younger participants or those with longer follow-up time between blood draw and NHL diagnosis. Conclusions We found only limited evidence of positive association between selected OCPs and development of NHL.
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- 2019
33. Survival After Secondary Cytoreductive Surgery and Chemotherapy Compared With Chemotherapy Alone for First Recurrence in Patients With Platinum-Sensitive Epithelial Ovarian Cancer and No Residuals After Primary Treatment. A Registry-Based Study
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Hilde Langseth, Claes G. Tropé, Janne Kærn, Tor A. Myklebust, Witold Szczesny, and T. Paulsen
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Oncology ,medicine.medical_specialty ,Chemotherapy ,endocrine system diseases ,business.industry ,Proportional hazards model ,medicine.medical_treatment ,Hazard ratio ,Obstetrics and Gynecology ,General Medicine ,female genital diseases and pregnancy complications ,Confidence interval ,Cancer registry ,Internal medicine ,Medicine ,In patient ,Stage (cooking) ,business ,First Recurrence - Abstract
Introduction The aim of this study was to investigate whether secondary cytoreductive surgery and platinum-based chemotherapy improved survival among patients with recurrent, platinum-sensitive epithelial ovarian cancer compared with those who received platinum-based chemotherapy alone, and to identify possible predictors for selection to secondary cytoreductive surgery. Material and methods We included 397 patients who had a primary diagnosis of FIGO stage I-IV epithelial ovarian cancer recorded in the Cancer Registry of Norway between 1 January 2002 and 31 December 2012, received primary surgery with no residuals followed by platinum-based chemotherapy, had first recurrence six or more months after completion of primary platinum-based chemotherapy, and received secondary treatment with either secondary cytoreductive surgery and platinum-based chemotherapy (secondary cytoreductive surgery+platinum-based chemotherapy group) or platinum-based chemotherapy alone (platinum-based chemotherapy group). Outcomes were progression-free survival to second recurrence or death and overall survival. Hazard ratios were estimated using multivariable Cox regression. Results There were 75 patients in the secondary cytoreductive surgery+platinum-based chemotherapy group in whom complete resection was achieved for 60 (80%), and 322 patients in the platinum-based chemotherapy group. Both progression-free survival (hazard ratio 0.45, 95% confidence interval 0.32-0.62) and overall survival (hazard ratio 0.50, 95% confidence interval 0.32-0.70) were improved in the secondary cytoreductive surgery+platinum-based chemotherapy compared with the platinum-based chemotherapy group. A survival benefit was only seen in patients with no residuals at secondary cytoreductive surgery. Conclusions In selected epithelial ovarian cancer patients with no residuals after primary surgery and a recurrent, platinum-sensitive tumor, the complete resection of recurrent tumor at secondary cytoreductive surgery improves progression-free survival and overall survival. Our results suggest that a long treatment-free interval and non-disseminated lesions (three or fewer lesions) on radiological images could be useful predictors for complete resection at secondary cytoreductive surgery.
- Published
- 2018
34. Association of Anti-Mullerian Hormone, Follicle-Stimulating Hormone, and Inhibin B with Risk of Ovarian Cancer in the Janus Serum Bank
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Hilde Langseth, Elisabete Weiderpass, Sarah R. Irvin, Nicolas Wentzensen, Louise A. Brinton, Britton Trabert, and Frank Z. Stanczyk
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0301 basic medicine ,Oncology ,Adult ,Anti-Mullerian Hormone ,medicine.medical_specialty ,endocrine system ,endocrine system diseases ,Epidemiology ,medicine.drug_class ,Risk Assessment ,Article ,03 medical and health sciences ,Follicle-stimulating hormone ,0302 clinical medicine ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Inhibins ,Prospective Studies ,Registries ,Ovarian reserve ,Prospective cohort study ,Biological Specimen Banks ,Ovarian Neoplasms ,biology ,business.industry ,Norway ,Ovary ,Case-control study ,Anti-Müllerian hormone ,medicine.disease ,female genital diseases and pregnancy complications ,030104 developmental biology ,Premenopause ,030220 oncology & carcinogenesis ,Case-Control Studies ,biology.protein ,Female ,Gonadotropin ,Follicle Stimulating Hormone ,Ovarian cancer ,business ,hormones, hormone substitutes, and hormone antagonists ,Hormone - Abstract
Background: Reproductive factors, including parity, breastfeeding, and contraceptive use, affect lifetime ovulatory cycles and cumulative exposure to gonadotropins and are associated with ovarian cancer. To understand the role of ovulation-regulating hormones in the etiology of ovarian cancer, we prospectively analyzed the association of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B with ovarian cancer risk. Methods: Our study included 370 women from the Janus Serum Bank, including 54 type I and 82 type II invasive epithelial ovarian cancers, 49 borderline tumors, and 185 age-matched controls. We used conditional logistic regression to assess the relationship between hormones and risk of ovarian cancer overall and by subtype (types I and II). Results: Inhibin B was associated with increased risk of ovarian cancer overall [OR, 1.97; 95% confidence interval (CI), 1.14–3.39; Ptrend = 0.05] and with type I ovarian (OR, 3.10; 95% CI, 1.04–9.23; Ptrend = 0.06). FSH was not associated with ovarian cancer risk overall, but higher FSH was associated with type II ovarian cancers (OR, 2.78; 95% CI, 1.05–7.38). AMH was not associated with ovarian cancer risk. Conclusions: FSH and inhibin B may be associated with increased risk in different ovarian cancer subtypes, suggesting that gonadotropin exposure may influence risk of ovarian cancer differently across subtypes. Impact: Associations between prospectively collected AMH, FSH, and inhibin B levels with risk of ovarian cancer provide novel insight on the influence of premenopausal markers of ovarian reserve and gonadotropin signaling. Heterogeneity of inhibin B and FSH effects in different tumor types may be informative of tumor etiology.
- Published
- 2019
35. Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium
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Aimée R. Kreimer, Roger L. Milne, William J. Blot, Alan Hildesheim, Carlotta Sacerdote, Eivind Ness-Jensen, Hilde Langseth, Lesley F. Tinker, Demetrius Albanes, Roel Vermeulen, Aurelio Barricarte, Gypsyamber D'Souza, Graham G. Giles, Wen-Yi Huang, Aida Ferreiro-Iglesias, Wei Zheng, Hilary A. Robbins, Stephanie J. Weinstein, Lea Schroeder, Giske Ursin, Anne Tjønneland, Neal D. Freedman, Michael Pawlita, Kala Visvanathan, Mattias Johansson, Judith Hoffman-Bolton, Mari Nygård, Kristian Hveem, Betty J. May, Elisabete Weiderpass, Qiuyin Cai, Ilir Agalliu, Antonia Trichopoulou, Nicolas F. Schlecht, Paul Brennan, Tim Waterboer, Nicole Brenner, Noemi Bender, Sylvia Smoller, Rudolf Kaaks, Department of Medical and Clinical Genetics, Faculty of Medicine, and University of Helsinki
- Subjects
0301 basic medicine ,Male ,Time Factors ,Carcinogenesis ,Epidemiology ,Antibodies, Viral ,Serology ,0302 clinical medicine ,DESIGN ,OPCSCC ,Prospective Studies ,Prospective cohort study ,RISK ,education.field_of_study ,Human papillomavirus 16 ,biology ,VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801 ,Hematology ,Middle Aged ,CANCER ,3. Good health ,Oropharyngeal Neoplasms ,Oncology ,Seroconversion ,030220 oncology & carcinogenesis ,Cohort ,Female ,Antibody ,HPVC3 ,Adult ,medicine.medical_specialty ,3122 Cancers ,Population ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,COHORT ,HEAD ,education ,Aged ,business.industry ,Squamous Cell Carcinoma of Head and Neck ,HUMAN-PAPILLOMAVIRUS ,Papillomavirus Infections ,Case-control study ,Cancer ,Oncogene Proteins, Viral ,Original Articles ,medicine.disease ,Repressor Proteins ,030104 developmental biology ,Case-Control Studies ,biology.protein ,oropharyngeal squamous cell carcinoma ,VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801 ,business ,Follow-Up Studies - Abstract
Background Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. Patients and methods We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6–11 years, range = 0–40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). Results HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1–155.4) in whites and 17.2-fold (95% CI 1.7–170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time 30 years (N = 24), 20–30 years (N = 148), 10–20 years (N = 228), and
- Published
- 2019
36. Circulating small non-coding RNAs associated with age, sex, smoking, body mass and physical activity
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Steinar Tretli, Robert Lyle, Giske Ursin, Sinan Uğur Umu, Eckart Meese, Hilde Langseth, Andreas Keller, and Trine B. Rounge
- Subjects
Adult ,Male ,0301 basic medicine ,Aging ,medicine.medical_treatment ,Physical activity ,lcsh:Medicine ,Physiology ,Biology ,Red Cross Blood Donors (RCBD) ,Article ,Body Mass Index ,Transcriptome ,03 medical and health sciences ,isomiRs ,microRNA ,medicine ,Humans ,RNA, Small Interfering ,Small nucleolar RNA ,lcsh:Science ,Exercise ,Blood Donor Group (BDg) ,Aged ,Genetics ,Messenger RNA ,Multidisciplinary ,Smoking ,lcsh:R ,RNA ,Middle Aged ,Non-coding RNA ,030104 developmental biology ,piRNAs ,Ageing ,Transfer RNA ,Janus Serum Bank (JSB) ,RNA, Small Untranslated ,Biomarker (medicine) ,Smoking cessation ,Female ,lcsh:Q ,Body mass index ,Small nuclear RNA - Abstract
Non-coding RNAs (ncRNA) are regulators of cell functions and circulating ncRNAs from the majority of RNA classes, such as miRNA, tRNA, piRNAs, lncRNA, snoRNA, snRNA and miscRNAs, are potential non-invasive biomarkers. Understanding how non-disease traits influence ncRNA expression is essential for assessing their biomarker potential.We studied associations of common traits (sex, age, smoking, body mass, physical activity, and technical factors such as sample storage and processing) with serum ncRNAs. We used RNAseq data from 526 donors from the Janus Serum Bank and traits from health examination surveys. We identified associations between all RNA classes and traits. Ageing showed the strongest association with ncRNA expression, both in terms of statistical significance and number of RNAs, regardless of RNA class. Serum processing modifications and storage times significantly altered expression levels of a number of ncRNAs. Interestingly, smoking cessation generally restored RNA expression to non-smoking levels, although for some isomiRs, mRNA fragments and tRNAs smoking-related expression levels persisted.Our results show that common traits influence circulating ncRNA expression. Therefore it is clear that ncRNA biomarker analyses should be adjusted for age and sex. In addition, for specific ncRNAs identified in our study, analyses should also be adjusted for body mass, smoking, physical activity and serum processing and storage.
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- 2018
37. Metabolomic screening of pre-diagnostic serum samples identifies association between α- and γ-tocopherols and glioblastoma risk
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Ulrika Andersson, Pär Jonsson, Beatrice Melin, Benny Björkblom, Henrik Antti, Lina Mörén, Hilde Langseth, Tom Børge Johannesen, and Carl Wibom
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Metabolite ,medicine.medical_treatment ,alpha-Tocopherol ,gamma-Tocopherol ,vitamin E ,Biology ,Pharmacology ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,serum metabolite ,0302 clinical medicine ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Metabolomics ,Hypoxanthine ,Cancer och onkologi ,Brain Neoplasms ,Vitamin E ,Case-control study ,Odds ratio ,Middle Aged ,population-based ,030104 developmental biology ,antioxidants ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Cancer and Oncology ,Case-Control Studies ,Female ,Sample collection ,Glioblastoma ,Oxidation-Reduction ,brain tumor ,Research Paper - Abstract
Glioblastoma is associated with poor prognosis with a median survival of one year. High doses of ionizing radiation is the only established exogenous risk factor. To explore new potential biological risk factors for glioblastoma, we investigated alterations in metabolite concentrations in pre-diagnosed serum samples from glioblastoma patients diagnosed up to 22 years after sample collection, and undiseased controls. The study points out a latent biomarker for future glioblastoma consisting of nine metabolites (gamma-tocopherol, alpha-tocopherol, erythritol, erythronic acid, myo-inositol, cystine, 2-keto-L-gluconic acid, hypoxanthine and xanthine) involved in antioxidant metabolism. We detected significantly higher serum concentrations of alpha-tocopherol (p=0.0018) and gamma-tocopherol (p=0.0009) in future glioblastoma cases. Compared to their matched controls, the cases showed a significant average fold increase of alpha- and gamma-tocopherol levels: 1.2 for alpha-T (p=0.018) and 1.6 for gamma-T (p=0.003). These tocopherol levels were associated with a glioblastoma odds ratio of 1.7 (alpha-T, 95% CI: 1.0-3.0) and 2.1 (gamma-T, 95% CI: 1.2-3.8). Our exploratory metabolomics study detected elevated serum levels of a panel of molecules with antioxidant properties as well as oxidative stress generated compounds. Additional studies are necessary to confirm the association between the observed serum metabolite pattern and future glioblastoma development.
- Published
- 2016
38. Longitudinal biobanks-based study on the joint effects of infections, nutrition and hormones on risk of prostate cancer
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Leena Tenkanen, Sonja Lumme, Pekka Saikku, Hilde Langseth, Pentti Tuohimaa, Randi Elin Gislefoss, Joakim Dillner, Ulf-Håkan Stenman, Matti Hakama, Herman Adlercreutz, Göran Hallmans, Tapio Luostarinen, and Pär Stattin
- Subjects
Male ,0301 basic medicine ,Oncology ,Chlamydia trachomatis ,Disease ,medicine.disease_cause ,Cohort Studies ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,4-Butyrolactone ,Risk Factors ,Testosterone ,Longitudinal Studies ,Vitamin D ,Finland ,Human papillomavirus 18 ,Norway ,Hematology ,General Medicine ,Middle Aged ,female genital diseases and pregnancy complications ,3. Good health ,030220 oncology & carcinogenesis ,Blood Banks ,Adult ,medicine.medical_specialty ,Lignans ,03 medical and health sciences ,Enterolactone ,Internal medicine ,medicine ,Vitamin D and neurology ,Humans ,Radiology, Nuclear Medicine and imaging ,Sweden ,business.industry ,Papillomavirus Infections ,Case-control study ,Prostatic Neoplasms ,Chlamydia Infections ,medicine.disease ,030104 developmental biology ,chemistry ,Case-Control Studies ,Nested case-control study ,Immunology ,business - Abstract
Background To evaluate the individual and combined effects of enterolactone, vitamin D, free testosterone, Chlamydia trachomatis and HPV-18 on the risk of prostate cancer in a large population-based biochemical material that combined three Nordic serum sample banks. Material and methods A joint cohort of 209 000 healthy men was followed using cancer registry linkages. From this cohort altogether 699 incident cases of prostate cancer were identified. Four controls were selected by incidence density sampling and matching for country, age and date of the blood sampling. Complete data for all investigated exposures was available for 483 eligible cases and 1055 eligible controls. Multivariate regression analyses were performed to investigate the solitary and combined effects. Results The solitary effects were small. Significantly increased risk [rate ratio 1.6 (95% CI 1.0-2.5)] was found in those seronegative for C. trachomatis infection. The joint effect in risk levels of enterolactone and vitamin D was antagonistic [observed rate ratio (RR) 1.4 (1.0-2.1), expected RR 2.0 (1.0-4.1)] as well as that of HPV-18 and C. trachomatis [observed RR 1.9 (0.8-4.5), expected RR 9.9 (1.1-87.0)]. Conclusion A large follow-up study combining data from several previously investigated exposures to investigate joint effects found no evidence that exposure to two risk factors would increase the risk of prostate cancer from that expected on basis of exposure to one risk factor. If anything, the results were consistent with antagonistic interactions.
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- 2016
39. Bayes and empirical Bayes methods for reduced rank regression models in matched case-control studies
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Ananda Sen, Lawrence S. Engel, Qing Lan, Qin Zhou, Nathaniel Rothman, Jaya M. Satagopan, and Hilde Langseth
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0301 basic medicine ,Statistics and Probability ,General Immunology and Microbiology ,Applied Mathematics ,Bayesian probability ,Estimator ,Regression analysis ,General Medicine ,Matched Case-Control Studies ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,Reduced rank regression ,010104 statistics & probability ,03 medical and health sciences ,Bayesian lasso ,Bayes' theorem ,030104 developmental biology ,Statistics ,Econometrics ,0101 mathematics ,General Agricultural and Biological Sciences ,Mathematics - Abstract
Matched case-control studies are popular designs used in epidemiology for assessing the effects of exposures on binary traits. Modern studies increasingly enjoy the ability to examine a large number of exposures in a comprehensive manner. However, several risk factors often tend to be related in a nontrivial way, undermining efforts to identify the risk factors using standard analytic methods due to inflated type-I errors and possible masking of effects. Epidemiologists often use data reduction techniques by grouping the prognostic factors using a thematic approach, with themes deriving from biological considerations. We propose shrinkage-type estimators based on Bayesian penalization methods to estimate the effects of the risk factors using these themes. The properties of the estimators are examined using extensive simulations. The methodology is illustrated using data from a matched case-control study of polychlorinated biphenyls in relation to the etiology of non-Hodgkin's lymphoma.
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- 2015
40. HE4 as an Early Detection Biomarker of Epithelial Ovarian Cancer: Investigations in Prediagnostic Specimens From the Janus Serumbank
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Kjell Nustad, Nils Bolstad, Lars Mørkrid, Hilde Langseth, and Randi Elin Gislefoss
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Oncology ,medicine.medical_specialty ,Pathology ,Time Factors ,Disease ,Carcinoma, Ovarian Epithelial ,chemistry.chemical_compound ,WAP Four-Disulfide Core Domain Protein 2 ,Internal medicine ,Carcinoma ,Humans ,Medicine ,Neoplasms, Glandular and Epithelial ,Cotinine ,Survival rate ,Early Detection of Cancer ,Biological Specimen Banks ,Tumor marker ,Ovarian Neoplasms ,Norway ,business.industry ,Smoking ,Case-control study ,Proteins ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,chemistry ,CA-125 Antigen ,Case-Control Studies ,Biomarker (medicine) ,Female ,business ,Ovarian cancer - Abstract
ObjectivesEpithelial ovarian cancer is characterized by nonspecific signs and clinical symptoms arising at late stages. Early detection is therefore important and may significantly improve the survival rate. Cancer antigen 125 (CA125) has been the most extensively studied serum biomarker in epithelial ovarian cancer, but low specificity limits its usefulness. A relatively novel biomarker, human epididymis protein 4 (HE4), has shown promise in early detection of the disease. The aim of this study was to investigate how early the tumor marker increases before diagnosis.Methods/MaterialsA nested case-control design was used to evaluate the performance of HE4 and CA125 in prediagnostic serum samples from the Janus Serumbank. Serial specimens from 120 women with invasive epithelial ovarian cancer were compared with healthy controls. Serum level of CA125, HE4, and cotinine was measured. Spearman correlation and multiple linear regression analyses were used to investigate impact of smoking, age, storage time, and lag time (time from sampling until date of diagnosis).ResultsSpearman correlation showed a strong positive correlation between HE4 and smoking in both cases and controls. Multiple linear regression analyses for pairwise differences between case and control showed that serum level of HE4 and CA125 was significantly increased (P= 0.002 andP< 0.001, respectively) 2 years before diagnosis and that CA125 also was significantly increased up to 4 years before diagnosis (P= 0.002).ConclusionsThe present study showed that a difference between cases and controls in serum concentration of HE4 seemed to be increased 2 years before diagnosis and that CA125 was increased until 4 years before diagnosis.
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- 2015
41. Prediagnostic Exposure to Polychlorinated Biphenyls and Organochlorine Pesticides and Thyroid Cancer in the Janus Serum Bank Cohort
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Tom Kristian Grimsrud, Hilde Langseth, Rena R. Jones, Lawrence S. Engel, Catherine C. Lerro, Mary H. Ward, and Andreas Sjödin
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endocrine system ,endocrine system diseases ,business.industry ,Thyroid ,Physiology ,Organochlorine pesticide ,medicine.disease ,medicine.anatomical_structure ,Cohort ,medicine ,General Earth and Planetary Sciences ,Endocrine system ,business ,Thyroid cancer ,General Environmental Science ,Hormone - Abstract
Background/Aim: Polychlorinated biphenyls (PCBs) and organochlorine insecticides (OC) have been associated with altered thyroid hormone levels in humans but their relationship with thyroid cancer i...
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- 2018
42. A nested case-control study of polychlorinated biphenyls, organochlorine pesticides, and thyroid cancer in the Janus Serum Bank cohort
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Mary H. Ward, Paul S. Albert, Tom Kristian Grimsrud, Rena R. Jones, Andreas Sjödin, Lawrence S. Engel, Hilde Langseth, Catherine C. Lerro, and Hyoyoung Choo-Wosoba
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Male ,Physiology ,Chlordane ,010501 environmental sciences ,01 natural sciences ,Biochemistry ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Hydrocarbons, Chlorinated ,Medicine ,Humans ,Thyroid Neoplasms ,Pesticides ,Thyroid cancer ,0105 earth and related environmental sciences ,General Environmental Science ,business.industry ,Norway ,Thyroid ,Hexachlorobenzene ,Odds ratio ,Environmental Exposure ,Pesticide ,medicine.disease ,Polychlorinated Biphenyls ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Case-Control Studies ,Cohort ,Nested case-control study ,Blood Banks ,Environmental Pollutants ,Female ,business - Abstract
Background Polychlorinated biphenyls (PCBs) and organochlorine pesticides have been associated with altered thyroid hormone levels in humans, but their relationship with thyroid cancer is unknown. Methods We conducted a nested case-control study of thyroid cancer in the Norwegian Janus Serum Bank cohort using pre-diagnostic blood samples from 1972 to 1985. Incident thyroid cancer (n = 108) was ascertained through 2008. Controls were matched 2:1 by age, date of blood draw, gender, and county. We used gas chromatography/mass spectrometry to quantify 36 PCB congeners and metabolites of pesticides DDT, chlordane, hexachlorocyclohexane, and hexachlorobenzene. PCBs and pesticide metabolites were evaluated individually and summed by degree of chlorination and parent compound, respectively. Odds ratios (OR) and 95% confidence intervals (CI) were computed using conditional logistic regression per specified increase in lipid-adjusted concentration. We additionally stratified analyses by birth cohort (1923–1932, 1933–1942, 1943–1957). Results Increasing concentration of DDT metabolites (ORper 1000 ng/g = 0.80, 95%CI = 0.66–0.98) was inversely associated with thyroid cancer. Associations for PCBs were null or in inverse direction. We observed interactions for total PCBs, moderately-chlorinated PCBs, and chlordane metabolites with birth cohort (p ≤ 0.04). Among participants born 1943–1957, total PCBs (ORper 100 ng/g = 1.25, 95%CI = 1.00–1.56), moderately-chlorinated PCBs (ORper 100 ng/g = 1.31, 95%CI = 1.01–1.70), and chlordane metabolites (ORper 10 ng/g = 1.78, 95%CI = 1.09–2.93) were positively associated with thyroid cancer. For individuals born before 1943, associations were generally null or in the inverse direction. Conclusions Emissions of PCBs and OC pesticides varied over time. Different risk patterns by birth cohort suggest the potential importance of timing of exposure in thyroid cancer risk. Further evaluation of these associations is warranted.
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- 2017
43. Investigation of Established Genetic Risk Variants for Glioma in Prediagnostic Samples from a Population-Based Nested Case–Control Study
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Carl Wibom, Eivind Hovig, Preetha Rajaraman, Hilde Langseth, Tom Børge Johannesen, Beatrice Melin, Ulrika Andersson, Florentin Späth, and Anna M. Dahlin
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Adult ,Male ,Epidemiology ,Nerve Tissue Proteins ,Genome-wide association study ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,law.invention ,Young Adult ,Risk Factors ,law ,Polymorphism (computer science) ,Glioma ,Humans ,Medicine ,Prospective Studies ,Registries ,Polymerase chain reaction ,Aged ,Genetic association ,Genetics ,Brain Neoplasms ,business.industry ,DNA Helicases ,Intracellular Signaling Peptides and Proteins ,Case-control study ,Genetic Variation ,Genes, erbB-1 ,Middle Aged ,medicine.disease ,Survival Rate ,Oncology ,Case-Control Studies ,Nested case-control study ,Etiology ,Female ,RNA, Long Noncoding ,Tumor Suppressor Protein p53 ,business - Abstract
Background: Although glioma etiology is poorly understood in general, growing evidence indicates a genetic component. Four large genome-wide association studies (GWAS) have linked common genetic variants with an increased glioma risk. However, to date, these studies are based largely on a case–control design, where cases have been recruited at the time of or after diagnosis. They may therefore suffer from a degree of survival bias, introduced when rapidly fatal cases are not included. Methods: To confirm glioma risk variants in a prospective setting, we have analyzed 11 previously identified risk variants in a set of prediagnostic serum samples with 598 cases and 595 matched controls. Serum samples were acquired from The Janus Serum Bank, a Norwegian population-based biobank reserved for cancer research. Results: We confirmed the association with glioma risk for variants within five genomic regions: 8q24.21 (CCDC26), 9p21.3 (CDKN2B-AS1), 11q23.3 (PHLDB1), 17p13.1 (TP53), and 20q13.33 (RTEL1). However, previously identified risk variants within the 7p11.2 (EGFR) region were not confirmed by this study. Conclusions: Our results indicate that the risk variants that were confirmed by this study are truly associated with glioma risk and may, consequently, affect gliomagenesis. Though the lack of positive confirmation of EGFR risk variants may be attributable to relatively limited statistical power, it nevertheless raises the question whether they truly are risk variants or markers for glioma prognosis. Impact: Our findings indicate the need for further studies to clarify the role of glioma risk loci with respect to prolonged survival versus etiology. Cancer Epidemiol Biomarkers Prev; 24(5); 810–6. ©2015 AACR.
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- 2015
44. Survival of women with cancers of breast and genital organs in Europe 1999–2007: Results of the EUROCARE-5 study
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Milena Sant, Maria Dolores Chirlaque Lopez, Roberto Agresti, Maria José Sánchez Pérez, Bernd Holleczek, Magdalena Bielska-Lasota, Nadya Dimitrova, Kaire Innos, Alexander Katalinic, Hilde Langseth, Nerea Larrañaga, Silvia Rossi, Sabine Siesling, Pamela Minicozzi, M. Hackl, N. Zielonke, W. Oberaigner, E. Van Eycken, K. Henau, Z. Valerianova, N. Dimitrova, M. Sekerija, M. Zvolský, L. Dušek, H. Storm, G. Engholm, M. Mägi, T. Aareleid, N. Malila, K. Seppä, M. Velten, X. Troussard, V. Bouvier, G. Launoy, A.V. Guizard, J. Faivre, A.M. Bouvier, P. Arveux, M. Maynadié, A.S. Woronoff, M. Robaszkiewicz, I. Baldi, A. Monnereau, B. Tretarre, N. Bossard, A. Belot, M. Colonna, F. Molinié, S. Bara, C. Schvartz, B. Lapôtre-Ledoux, P. Grosclaude, M. Meyer, R. Stabenow, S. Luttmann, A. Eberle, H. Brenner, A. Nennecke, J. Engel, G. Schubert-Fritschle, J. Kieschke, J. Heidrich, B. Holleczek, A. Katalinic, J.G. Jónasson, L. Tryggvadóttir, H. Comber, G. Mazzoleni, A. Bulatko, C. Buzzoni, A. Giacomin, A. Sutera Sardo, P. Mancuso, S. Ferretti, E. Crocetti, A. Caldarella, G. Gatta, M. Sant, H. Amash, C. Amati, P. Baili, F. Berrino, S. Bonfarnuzzo, L. Botta, F. Di Salvo, R. Foschi, C. Margutti, E. Meneghini, P. Minicozzi, A. Trama, D. Serraino, L. Dal Maso, R. De Angelis, M. Caldora, R. Capocaccia, E. Carrani, S. Francisci, S. Mallone, D. Pierannunzio, P. Roazzi, S. Rossi, M. Santaquilani, A. Tavilla, F. Pannozzo, S. Busco, L. Bonelli, M. Vercelli, V. Gennaro, P. Ricci, M. Autelitano, G. Randi, M. Ponz De Leon, C. Marchesi, C. Cirilli, M. Fusco, M.F. Vitale, M. Usala, A. Traina, R. Staiti, F. Vitale, B. Ravazzolo, M. Michiara, R. Tumino, P. Giorgi Rossi, E. Di Felice, F. Falcini, A. Iannelli, O. Sechi, R. Cesaraccio, S. Piffer, A. Madeddu, F. Tisano, S. Maspero, A.C. Fanetti, R. Zanetti, S. Rosso, P. Candela, T. Scuderi, F. Stracci, F. Bianconi, G. Tagliabue, P. Contiero, A.P. Dei Tos, S. Guzzinati, S. Pildava, G. Smailyte, N. Calleja, D. Agius, T.B. Johannesen, J. Rachtan, S. Gózdz, R. Mezyk, J. Blaszczyk, M. Bebenek, M. Bielska-Lasota, G. Forjaz de Lacerda, M.J. Bento, C. Castro, A. Miranda, A. Mayer-da-Silva, F. Nicula, D. Coza, C. Safaei Diba, M. Primic-Zakelj, E. Almar, C. Ramírez, M. Errezola, J. Bidaurrazaga, A. Torrella-Ramos, J.M. Díaz García, R. Jimenez-Chillaron, R. Marcos-Gragera, A. Izquierdo Font, M.J. Sanchez, D.Y.L. Chang, C. Navarro, M.D. Chirlaque, C. Moreno-Iribas, E. Ardanaz, J. Galceran, M. Carulla, M. Lambe, S. Khan, M. Mousavi, C. Bouchardy, M. Usel, S.M. Ess, H. Frick, M. Lorez, C. Herrmann, A. Bordoni, A. Spitale, I. Konzelmann, O. Visser, V. Lemmens, M. Coleman, C. Allemani, B. Rachet, J. Verne, N. Easey, G. Lawrence, T. Moran, J. Rashbass, M. Roche, J. Wilkinson, A. Gavin, C. Donnelly, D.H. Brewster, D.W. Huws, C. White, R. Otter, Health Technology & Services Research, and Faculty of Behavioural, Management and Social Sciences
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Gynecology ,Cervical cancer ,Cancer Research ,medicine.medical_specialty ,education.field_of_study ,Vaginal cancer ,Relative survival ,business.industry ,Obstetrics ,Population ,Cancer ,Breast cancer ,Corpus uteri cancer ,Europe ,Ovarian cancer ,Population-based ,Survival ,Vulval cancer ,Vulvar cancer ,medicine.disease ,medicine.anatomical_structure ,Oncology ,medicine ,METIS-311843 ,IR-97294 ,business ,education ,Cervix - Abstract
BACKGROUND: Survival differences across Europe for patients with cancers of breast, uterus, cervix, ovary, vagina and vulva have been documented by previous EUROCARE studies. In the present EUROCARE-5 study we update survival estimates and investigate changes in country-specific and over time survival, discussing their relationship with incidence and mortality dynamics for cancers for which organised screening programs are ongoing. METHODS: We analysed cases archived in over 80 population-based cancer registries in 29 countries grouped into five European regions. We used the cohort approach to estimate 5-year relative survival (RS) for adult (⩾15years) women diagnosed 2000-2007, by age, country and region ; and the period approach to estimate time trends (1999-2007) in RS for breast and cervical cancers. RESULTS: In 2000-2007, 5-year RS was 57% overall, 82% for women diagnosed with breast, 76% with corpus uteri, 62% with cervical, 38% with ovarian, 40% with vaginal and 62% with vulvar cancer. Survival was low for patients resident in Eastern Europe (34% ovary-74% breast) and Ireland and the United Kingdom [Ireland/UK] (31-79%) and high for those resident in Northern Europe (41-85%) except Denmark. Survival decreased with advancing age: markedly for women with ovarian (71% 15-44years ; 20% ⩾75years) and breast (86% ; 72%) cancers. Survival for patients with breast and cervical cancers increased from 1999-2001 to 2005-2007, remarkably for those resident in countries with initially low survival. CONCLUSIONS: Despite increases over time, survival for women's cancers remained poor in Eastern Europe, likely due to advanced stage at diagnosis and/or suboptimum access to adequate care. Low survival for women living in Ireland/UK and Denmark could indicate late detection, possibly related also to referral delay. Poor survival for ovarian cancer across the continent and over time suggests the need for a major research effort to improve prognosis for this common cancer.
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- 2015
45. A comprehensive profile of circulating RNAs in human serum
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Robert Lyle, Trine B. Rounge, Bastian Fromm, Marianne Lauritzen, Cecilie Bucher-Johannessen, Andreas Keller, Hilde Langseth, Sinan Uğur Umu, Eckart Meese, and Magnus Leithaug
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FOS: Computer and information sciences ,Vault RNA ,0301 basic medicine ,Small RNA ,Bioinformatics ,RNA Stability ,Piwi-interacting RNA ,Biology ,RNA fragments ,03 medical and health sciences ,RNA, Transfer ,microRNA ,rna sequencing ,cancer ,Humans ,RNA, Small Nucleolar ,Guide RNA ,RNA, Small Interfering ,Small nucleolar RNA ,Molecular Biology ,Sequence Analysis, RNA ,High-Throughput Nucleotide Sequencing ,RNA ,Cell Biology ,Argonaute ,Non-coding RNA ,Research Papers ,Molecular biology ,Long non-coding RNA ,MicroRNAs ,RNA silencing ,030104 developmental biology ,Gene Expression Regulation ,Biochemistry ,Transfer RNA ,RNA, Small Untranslated ,circulating RNA ,serum ,Cell-Free Nucleic Acids ,Biomarkers ,Small nuclear RNA - Abstract
Non-coding RNA (ncRNA) molecules have fundamental roles in cells and many are also stable in body fluids as extracellular RNAs. In this study, we used RNA sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA) in human serum. We analyzed 10 billion lllumina reads from 477 serum samples, included in the Norwegian population-based Janus Serum Bank (JSB). We found that the core serum RNA repertoire includes 258 micro RNAs (miRNA), 441 piwi-interacting RNAs (piRNA), 411 transfer RNAs (tRNA), 24 small nucleolar RNAs (snoRNA), 125 small nuclear RNAs (snRNA) and 123 miscellaneous RNAs (misc-RNA). We also investigated biological and technical variation in expression, and the results suggest that many RNA molecules identified in serum contain signs of biological variation. They are therefore unlikely to be random degradation by-products. In addition, the presence of specific fragments of tRNA, snoRNA, Vault RNA and Y_RNA indicates protection from degradation. Our results suggest that many circulating RNAs in serum can be potential biomarkers.
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- 2017
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46. Sources to variability in circulating human miRNA signatures
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Trine B. Rounge, Nicole Ludwig, Andreas Keller, Eckart Meese, Christina Backes, Hilde Langseth, Randi Elin Gislefoss, and Petra Leidinger
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0301 basic medicine ,RNA Stability ,Computational biology ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,microRNA ,Biomarkers, Tumor ,Humans ,Circulating MicroRNA ,Molecular Biology ,Life span ,Gene Expression Profiling ,Age Factors ,Cell Biology ,Serum samples ,MicroRNAs ,030104 developmental biology ,Blood donor ,030220 oncology & carcinogenesis ,Healthy individuals ,Immunology ,Biomarker (medicine) ,DNA microarray ,Transcriptome ,Biomarkers ,Research Paper - Abstract
An increasing number of studies propose circulating microRNAs (miRNAs) as biomarkers for a large number of human diseases including cancer, cardiovascular diseases, neurologic pathologies and others. To further validate miRNA as biomarkers it is indispensable to understand the variability of circulating miRNAs in healthy individuals. We determined the longitudinal miRNomes of 90 serum samples from the Janus Serum Bank in Norway, which have been stored between 23 and 40 y at -25 °Celsius. We profiled 3 serum samples with microarrays for 30 individuals, each. For each individual the samples were collected with a time interval of approximately 5 y. This design allowed insights into inter-individual variability, age dependent miRNA variability and the impact of storage length and pre-processing. A significant proportion of the miRNome was affected by the age of the blood donor and a not negligible, albeit small, part of the miRNome by the storage time. A substantial part of miRNAs was differentially abundant between individuals, independent of the time when samples were collected. Stepwise filtering of the 529 miRNAs that were detected in the serum samples showed 168 miRNAs with differential abundance depending on the time point analyzed, 56 miRNAs differentially abundant between individuals, and 169 miRNAs with an abundance depending on the sampling procedure. While these groups of miRNAs contain generally interesting and biologically important miRNAs, the remaining 135 miRNAs constitute very promising biomarker candidates as they show an overall low variability between healthy individuals, a likewise overall low variability across a longer life span, and a high independence of the sampling process and the storage length.
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- 2017
47. Pre-diagnostic dynamic HPV16 IgG seropositivity and risk of oropharyngeal cancer
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Jon Mork, Garrick Wallstrom, Diego Chowell, Julia N. Cheng, Rizwan Alam, Ingegerd E. Furre, Marshall R. Posner, Karen S. Anderson, and Hilde Langseth
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0301 basic medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Logistic regression ,Antibodies, Viral ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Multiple time ,Humans ,Human papillomavirus 16 ,biology ,business.industry ,Head and neck cancer ,Odds ratio ,Middle Aged ,medicine.disease ,stomatognathic diseases ,Oropharyngeal Neoplasms ,030104 developmental biology ,030220 oncology & carcinogenesis ,Clinical diagnosis ,Immunoglobulin G ,Cohort ,biology.protein ,Female ,Oral Surgery ,Antibody ,business - Abstract
The aim of this study was to determine the association of HPV16 antibodies (Abs) and oropharyngeal cancer (OPC) risk in sera obtained prior to clinical diagnosis.We identified 92 participants with incident OPC and 460 matched controls from the Janus Serum Bank Cohort in Norway. Archived tumor specimens were requested for a subset of the cases. Serum samples were collected from cases, on average, 9.3years before diagnosis (range, 0.1-14.9years). Ten cases had serum samples from multiple time points. IgG seropositivity to 8 HPV16 antigens was determined, and a logistic regression classifier of a panel of all early-antigen (EA) Abs for the predictive diagnosis of OPC was applied.HPV16 EA seropositivity was present in 25.0% of patients with OPC and 7.6% of controls (odds ratio (OR), 4.1; 95% CI, 2.3-7.2, p0.0001). Abs to E2 were strongly associated with cases 0-2years pre- diagnosis (OR, 150.1; 95% CI, 27.4-1040.0, p0.0001), and the probability of seropositivity was inversely associated with time to diagnosis (OR, 0.7 per additional year; 95% CI, 0.6-0.9, p=0.0002). Abs to E2 were also strongly associated with tumor HPV status (OR, 35.6; 95% CI, 8.7-200.0, p0.0001). A positive score on the binary classifier was associated with an overall OR of 15.8 (95% CI, 5.6-53.4) compared with controls (p0.05), and was strongly associated with tumor HPV status (OR, 27.4; 95% CI, 8.6-99.6, p0.001).HPV16 Abs are detectable years prior to diagnosis of OPC, and the probability of seropositivity increases closer to diagnosis.
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- 2017
48. Survival after secondary cytoreductive surgery and chemotherapy compared with chemotherapy alone for first recurrence in patients with platinum-sensitive epithelial ovarian cancer and no residuals after primary treatment. A registry-based study
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Hilde Langseth, Janne Kærn, Claes G. Tropé, Tor A. Myklebust, Witold Szczesny, and T. Paulsen
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Oncology ,Chemotherapy ,medicine.medical_specialty ,endocrine system diseases ,business.industry ,Proportional hazards model ,medicine.medical_treatment ,Hazard ratio ,Obstetrics and Gynecology ,General Medicine ,female genital diseases and pregnancy complications ,Confidence interval ,Cancer registry ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,In patient ,Epithelial ovarian cancer ,030212 general & internal medicine ,Stage (cooking) ,business - Abstract
Introduction The aim of this study was to investigate whether secondary cytoreductive surgery and platinum-based chemotherapy improved survival among patients with recurrent, platinum-sensitive epithelial ovarian cancer compared with those who received platinum-based chemotherapy alone, and to identify possible predictors for selection to secondary cytoreductive surgery. Material and methods We included 397 patients who had a primary diagnosis of FIGO stage I-IV epithelial ovarian cancer recorded in the Cancer Registry of Norway between 1 January 2002 and 31 December 2012, received primary surgery with no residuals followed by platinum-based chemotherapy, had first recurrence six or more months after completion of primary platinum-based chemotherapy, and received secondary treatment with either secondary cytoreductive surgery and platinum-based chemotherapy (secondary cytoreductive surgery+platinum-based chemotherapy group) or platinum-based chemotherapy alone (platinum-based chemotherapy group). Outcomes were progression-free survival to second recurrence or death and overall survival. Hazard ratios were estimated using multivariable Cox regression. Results There were 75 patients in the secondary cytoreductive surgery+platinum-based chemotherapy group in whom complete resection was achieved for 60 (80%), and 322 patients in the platinum-based chemotherapy group. Both progression-free survival (hazard ratio 0.45, 95% confidence interval 0.32-0.62) and overall survival (hazard ratio 0.50, 95% confidence interval 0.32-0.70) were improved in the secondary cytoreductive surgery+platinum-based chemotherapy compared with the platinum-based chemotherapy group. A survival benefit was only seen in patients with no residuals at secondary cytoreductive surgery. Conclusions In selected epithelial ovarian cancer patients with no residuals after primary surgery and a recurrent, platinum-sensitive tumor, the complete resection of recurrent tumor at secondary cytoreductive surgery improves progression-free survival and overall survival. Our results suggest that a long treatment-free interval and non-disseminated lesions (three or fewer lesions) on radiological images could be useful predictors for complete resection at secondary cytoreductive surgery.
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- 2017
49. Effect of multiple freeze-thaw cycles on selected biochemical serum components
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Lars Mørkrid, Marianne Lauritzen, Hilde Langseth, and Randi Elin Gislefoss
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Time Factors ,Bilirubin ,Sodium ,Clinical Biochemistry ,chemistry.chemical_element ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Thyroid-stimulating hormone ,Internal medicine ,Freezing ,medicine ,Humans ,Vitamin B12 ,Testosterone ,Creatinine ,Blood Specimen Collection ,Cholesterol ,Biochemistry (medical) ,Albumin ,General Medicine ,Fasting ,Middle Aged ,030104 developmental biology ,Endocrinology ,chemistry ,030220 oncology & carcinogenesis ,Immunology ,Female ,Blood Chemical Analysis - Abstract
Background:To maintain the best performance a frozen serum sample should be thawed once to prevent repeated freeze-thaw cycles. Archival biobanks often have one tube of a sample available, causing repeated freeze-thaw cycles when the sample is used in multiple research projects. In this study, we investigated potential effects of freeze-thaw cycles on several biochemical components in serum.Methods:Serum from 40 fasting donors of both genders, aged 30–60 years, were frozen at –25 °C. Aliquots of the 40 different samples went through 1, 2, 3, 4, 5 and 10 thaws, respectively. They were analyzed after 3 month of storage for 15 serum components including electrolytes and metabolites, proteins and enzymes, lipids, hormones and vitamins. One-way analyses of variance (ANOVA) with repeated measurements and equivalence tests were used to examine differences in component levels.Results:Albumin, aspartate-aminotransferase (ASAT), cholesterol, creatinine, C-reactive protein, glucose, immunoglobulin G, potassium, testosterone, triglycerides, urea and vitamin B12 levels did not show significant difference for pairwise comparisons after 10 repeated thaws. Although albumin, ASAT, bilirubin, potassium, sodium, testosterone and thyroid stimulating hormone (TSH) showed overall statistically significant changes in serum levels, only bilirubin, sodium and TSH were significant for the pairwise comparisons investigated. Clinical significance were shown for albumin, ASAT, bilirubin, sodium and testosterone.Conclusions:Twelve components (albumin, ASAT, cholesterol, creatinine, C-reactive protein, glucose, immunoglobulin G, potassium, testosterone, triglycerides, urea and vitamin B12) were robust to 10 repeated thaws compared to baseline level. Three components (bilirubin, sodium and TSH) showed statistical significant difference for pairwise comparisons, however, TSH was not clinically affected.
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- 2016
50. PO-073 Small non-coding RNA in serum from testicular germ cell tumour patientsidentified by machine learning
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J. Burton, Trine B. Rounge, Tom Kristian Grimsrud, Tom Grotmol, Sinan Uğur Umu, Trine B. Haugen, H. Hammer, and Hilde Langseth
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Cancer Research ,business.industry ,Decision tree ,Biology ,medicine.disease ,Machine learning ,computer.software_genre ,Malignancy ,Oncology ,Lasso (statistics) ,Linear regression ,medicine ,Genetic predisposition ,Artificial intelligence ,business ,computer ,Testicular cancer ,Blood sampling ,Genetic association - Abstract
Introduction Testicular germ cell tumour (TGCT) is a malignancy present in males with the highest incidence rates in younger age ranges. The aetiology is still largely unknown; however, several genome-wide association studies have identified up to 30 independent loci influencing TGCT risk, confirming its inherited genetic susceptibility. Machine learning can be utilised as a modelling technique to identify patterns within genetic and lifestyle data that allows classification and identification of biomarkers. We aim to identify potential biomarkers and perform accurate classifications in the small non-coding RNAs (sncRNAs) of 147 pre-diagnostic serum samples. Material and methods The serum samples were obtained from the Janus Serum Bank, with life-style covariates, such as smoking habits, BMI and exercise habits also recorded for each sample. A total of 69 TGCT samples and 78 control sample sncRNA reads were used to train machine learning algorithms including linear regression, LASSO, decision trees and neural networks. These cases and controls are matched by age at blood sampling. Results and discussions Preliminary results from LASSO and decision tree methods show differentiation in the miRNA/piRNA patterns between the control and the TGCT samples after adjusting individual read counts for age at sampling. Classification performance was better when trained using piRNAs, 58% of control samples were classified as normal and 60% of TGCT cases being classified as TGCT patients. Further inclusion of life-style covariates in the model as well as age and time of diagnosis is still to be performed to increase classification performance further. By using interpretable machine learning methods, we aim to identify biomarkers that allow the accurate classification of the samples. Conclusion These results show that the piRNA composition seen in pre-diagnostic serum samples may contain potential biomarkers that can lead to accurate classification of whether a patient was at increased risk of testicular cancer before the initial diagnosis. Preliminary results should be further expanded with different sncRNA datasets and lifestyle covariates.
- Published
- 2018
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