Author: "Eleonora Fabianova" / Publication Year Range: Last 10 years - Searchworks@Jio Institute Digital Library Search Results

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56 results on '"Eleonora Fabianova"'

1. Respirable crystalline silica and lung cancer in community-based studies: impact of job-exposure matrix specifications on exposure–response relationships

Author: Johan Ohlander, Hans Kromhout, Roel Vermeulen, Lützen Portengen, Benjamin Kendzia, Barbara Savary, Domenico Cavallo, Andrea Cattaneo, Enrica Migliori, Lorenzo Richiardi, Nils Plato, Heinz-Erich Wichmann, Stefan Karrasch, Dario Consonni, Maria Teresa Landi, Neil E Caporaso, Jack Siemiatycki, Per Gustavsson, Karl-Heinz Jöckel, Wolfgang Ahrens, Hermann Pohlabeln, Guillermo Fernández-Tardón, David Zaridze, Jolanta Lissowska Jolanta Lissowska, Beata Swiatkowska Beata Swiatkowska, John K Field John K Field, John R McLaughlin, Paul A Demers, Tamas Pandics, Francesco Forastiere, Eleonora Fabianova, Miriam Schejbalova, Lenka Foretova, Vladimir Janout, Dana Mates, Christine Barul, Thomas Brüning, Thomas Behrens, Kurt Straif, Joachim Schüz, Ann Olsson, and Susan Peters
Subjects: case-control study, cancer, lung cancer, job-exposure matrix, general population, lung neoplasm, jem, quantitative exposure assessment, exposure–response, respirable crystalline silica, respirable quartz exposure, Public aspects of medicine, RA1-1270
Abstract: OBJECTIVES: The quantitative job-exposure matrix SYN-JEM consists of various dimensions: job-specific estimates, region-specific estimates, and prior expert ratings of jobs by the semi-quantitative DOM-JEM. We analyzed the effect of different JEM dimensions on the exposure–response relationships between occupational silica exposure and lung cancer risk to investigate how these variations influence estimates of exposure by a quantitative JEM and associated health endpoints. METHODS: Using SYN-JEM, and alternative SYN-JEM specifications with varying dimensions included, cumulative silica exposure estimates were assigned to 16 901 lung cancer cases and 20 965 controls pooled from 14 international community-based case-control studies. Exposure–response relationships based on SYN-JEM and alternative SYN-JEM specifications were analyzed using regression analyses (by quartiles and log-transformed continuous silica exposure) and generalized additive models (GAM), adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk. RESULTS: SYN-JEM and alternative specifications generated overall elevated and similar lung cancer odds ratios ranging from 1.13 (1st quartile) to 1.50 (4th quartile). In the categorical and log-linear analyses SYN-JEM with all dimensions included yielded the best model fit, and exclusion of job-specific estimates from SYN-JEM yielded the poorest model fit. Additionally, GAM showed the poorest model fit when excluding job-specific estimates. CONCLUSION: The established exposure–response relationship between occupational silica exposure and lung cancer was marginally influenced by varying the dimensions of SYN-JEM. Optimized modelling of exposure–response relationships will be obtained when incorporating all relevant dimensions, namely prior rating, job, time, and region. Quantitative job-specific estimates appeared to be the most prominent dimension for this general population JEM.
Published: 2024
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2. Corrigendum: Temporal trends of COVID-19 antibodies in vaccinated healthcare workers undergoing repeated serological sampling: an individual-level analysis within 13 months in the ORCHESTRA cohort

Author: Giulia Collatuzzo, Giuseppe De Palma, Francesco S. Violante, Stefano Porru, Francesca Larese Filon, Eleonora Fabianova, Concepción Violán, Luigi Vimercati, Mihaela Leustean, Marta Maria Rodriguez-Suarez, Emanuele Sansone, Emma Sala, Carlotta Zunarelli, Vittorio Lodi, Maria Grazia Lourdes Monaco, Gianluca Spiteri, Corrado Negro, Jana Beresova, LucÌa A. Carrasco-Ribelles, Silvio Tafuri, Shuffield S. Asafo, Giorgia Ditano, Mahsa Abedini, and Paolo Boffetta
Subjects: serial serology, antibodies, temporal trends, COVID-19 vaccination, health care workers, Immunologic diseases. Allergy, RC581-607
Published: 2023
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3. Temporal trends of COVID-19 antibodies in vaccinated healthcare workers undergoing repeated serological sampling: An individual-level analysis within 13 months in the ORCHESTRA cohort

Author: Giulia Collatuzzo, Giuseppe De Palma, Francesco S. Violante, Stefano Porru, Francesca Larese Filon, Eleonora Fabianova, Concepción Violán, Luigi Vimercati, Mihaela Leustean, Marta Maria Rodriguez-Suarez, Emanuele Sansone, Emma Sala, Carlotta Zunarelli, Vittorio Lodi, Maria Grazia Lourdes Monaco, Gianluca Spiteri, Corrado Negro, Jana Beresova, LucÌa A. Carrasco-Ribelles, Silvio Tafuri, Shuffield S. Asafo, Giorgia Ditano, Mahsa Abedini, and Paolo Boffetta
Subjects: serial serology, antibodies, temporal trends, COVID-19 vaccination, health care workers, Immunologic diseases. Allergy, RC581-607
Abstract: Short summaryWe investigated changes in serologic measurements after COVID-19 vaccination in 19,422 subjects. An individual-level analysis was performed on standardized measurements. Age, infection, vaccine doses, time between doses and serologies, and vaccine type were associated with changes in serologic levels within 13 months.BackgroundPersistence of vaccine immunization is key for COVID-19 prevention.MethodsWe investigated the difference between two serologic measurements of anti-COVID-19 S1 antibodies in an individual-level analysis on 19,422 vaccinated healthcare workers (HCW) from Italy, Spain, Romania, and Slovakia, tested within 13 months from first dose. Differences in serologic levels were divided by the standard error of the cohort-specific distribution, obtaining standardized measurements. We fitted multivariate linear regression models to identify predictors of difference between two measurements.ResultsWe observed a progressively decreasing difference in serologic levels from
Published: 2023
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4. Application of two job indices for general occupational demands in a pooled analysis of case–control studies on lung cancer

Author: Jan Hovanec, Jack Siemiatycki, David I Conway, Ann Olsson, Pascal Guenel, Danièle Luce, Karl-Heinz Jöckel, Hermann Pohlabeln, Wolfgang Ahrens, Stefan Karrasch, Heinz-Erich Wichmann, Per Gustavsson, Dario Consonni, Franco Merletti, Lorenzo Richiardi, Simonato Lorenzo, Cristina Fortes, Marie-Élise Parent, John R McLaughlin, Paul Demers, Maria Teresa Landi, Neil Caporaso, Guillermo Fernández-Tardón, David Zaridze, Beata Świątkowska, Tamas Pándics, Jolanta Lissowska, Eleonora Fabianova, John K Field, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Hans Kromhout, Roel Vermeulen, Paolo Boffetta, Kurt Straif, Joachim Schüz, Swaantje Casjens, Beate Pesch, Thomas Brüning, and Thomas Behrens
Subjects: cancer, smoking, lung cancer, psychosocial, job index, case–control, tumor subtype, social prestige, occupational demand, Public aspects of medicine, RA1-1270
Abstract: OBJECTIVES: We investigated general job demands as a risk factor for lung cancer as well as their role in the association between occupational prestige and lung cancer. METHODS: In 13 case–control studies on lung cancer, as part of the international SYNERGY project, we applied indices for physical (PHI) and psychosocial (PSI) job demands – each with four categories (high to low). We estimated odds ratios (OR) and 95% confidence intervals (CI) for lung cancer by unconditional logistic regression, separately for men and women and adjusted for study centre, age, smoking behavior, and former employment in occupations with potential exposure to carcinogens. Further, we investigated, whether higher risks among men with low occupational prestige (Treiman’s Standard International Occupational Prestige Scale) were affected by adjustment for the job indices. RESULTS: In 30 355 men and 7371 women, we found increased risks (OR) for lung cancer with high relative to low job demands in both men [PHI 1.74 (95% CI 1.56–1.93), PSI 1.33 (95% CI 1.17–1.51)] and women [PHI 1.62 (95% CI 1.24–2.11), PSI 1.31 (95% CI 1.09–1.56)]. OR for lung cancer among men with low occupational prestige were slightly reduced when adjusting for PHI [low versus high prestige OR from 1.44 (95% CI 1.32–1.58) to 1.30 (95% CI 1.17–1.45)], but not PSI. CONCLUSIONS: Higher physical job demands were associated with increased risks of lung cancer, while associations for higher psychosocial demands were less strong. In contrast to physical demands, psychosocial demands did not contribute to clarify the association of occupational prestige and lung cancer.
Published: 2021
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5. Determinants of Anti-S Immune Response at 9 Months after COVID-19 Vaccination in a Multicentric European Cohort of Healthcare Workers—ORCHESTRA Project

Author: Giulia Collatuzzo, Vittorio Lodi, Daniela Feola, Giuseppe De Palma, Emanuele Sansone, Emma Sala, Christian Janke, Noemi Castelletti, Stefano Porru, Gianluca Spiteri, Maria Grazia Lourdes Monaco, Francesca Larese Filon, Corrado Negro, Luca Cegolon, Jana Beresova, Eleonora Fabianova, Lucia A. Carrasco-Ribelles, Pere Toràn-Monserrat, Marta Maria Rodriguez-Suarez, Guillermo Fernandez-Tardon, Shuffield S. Asafo, Giorgia Ditano, Mahsa Abedini, and Paolo Boffetta
Subjects: COVID-19, vaccine, serology, antibody level, immunization, temporal trends, Microbiology, QR1-502
Abstract: Background: The persistence of antibody levels after COVID-19 vaccination has public health relevance. We analyzed the determinants of quantitative serology at 9 months after vaccination in a multicenter cohort. Methods: We analyzed data on anti-SARS-CoV-2 spike antibody levels at 9 months from the first dose of vaccinated HCW from eight centers in Italy, Germany, Spain, Romania and Slovakia. Serological levels were log-transformed to account for the skewness of the distribution and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log antibody level and the corresponding 95% confidence interval (CI), and combined them in random-effects meta-analyses. Finally, we conducted a trend analysis of 1 to 7 months’ serology within one cohort. Results: We included 20,216 HCW with up to two vaccine doses and showed that high antibody levels were associated with female sex (p = 0.01), age (RR = 0.87, 95% CI = 0.86–0.88 per 10-year increase), 10-day increase in time since last vaccine (RR = 0.97, 95% CI 0.97–0.98), previous infection (3.03, 95% CI = 2.92–3.13), two vaccine doses (RR = 1.22, 95% CI = 1.09–1.36), use of Spikevax (OR = 1.51, 95% CI = 1.39–1.64), Vaxzevria (OR = 0.57, 95% CI = 0.44–0.73) or heterologous vaccination (OR = 1.33, 95% CI = 1.12–1.57), compared to Comirnaty. The trend in the Bologna cohort, based on 3979 measurements, showed a decrease in mean standardized antibody level from 8.17 to 7.06 (1–7 months, p for trend 0.005). Conclusions: Our findings corroborate current knowledge on the determinants of COVID-19 vaccine-induced immunity and declining trend with time.
Published: 2022
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6. Circulating tumour-derived KRAS mutations in pancreatic cancer cases are predominantly carried by very short fragments of cell-free DNA

Author: Maria Zvereva, Gabriel Roberti, Geoffroy Durand, Catherine Voegele, Minh Dao Nguyen, Tiffany M. Delhomme, Priscilia Chopard, Eleonora Fabianova, Zora Adamcakova, Ivana Holcatova, Lenka Foretova, Vladimir Janout, Paul Brennan, Matthieu Foll, Graham B. Byrnes, James D. McKay, Ghislaine Scelo, and Florence Le Calvez-Kelm
Subjects: Cell-free DNA, KRAS mutations, Plasma, Pancreatic cancer detection, Medicine, Medicine (General), R5-920
Abstract: Background: The DNA released into the bloodstream by malignant tumours· called circulating tumour DNA (ctDNA), is often a small fraction of total cell-free DNA shed predominantly by hematopoietic cells and is therefore challenging to detect. Understanding the biological properties of ctDNA is key to the investigation of its clinical relevance as a non-invasive marker for cancer detection and monitoring. Methods: We selected 40 plasma DNA samples of pancreatic cancer cases previously reported to carry a KRAS mutation at the ‘hotspot’ codon 12 and re-screened the cell-free DNA using a 4-size amplicons strategy (57 bp, 79 bp, 167 bp and 218 bp) combined with ultra-deep sequencing in order to investigate whether amplicon lengths could impact on the capacity of detection of ctDNA, which in turn could provide inference of ctDNA and non-malignant cell-free DNA size distribution. Findings: Higher KRAS amplicon size (167 bp and 218 bp) was associated with lower detectable cell-free DNA mutant allelic fractions (p
Published: 2020
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7. Genome-wide association study identifies multiple risk loci for renal cell carcinoma

Author: Ghislaine Scelo, Mark P. Purdue, Kevin M. Brown, Mattias Johansson, Zhaoming Wang, Jeanette E. Eckel-Passow, Yuanqing Ye, Jonathan N. Hofmann, Jiyeon Choi, Matthieu Foll, Valerie Gaborieau, Mitchell J. Machiela, Leandro M. Colli, Peng Li, Joshua N. Sampson, Behnoush Abedi-Ardekani, Celine Besse, Helene Blanche, Anne Boland, Laurie Burdette, Amelie Chabrier, Geoffroy Durand, Florence Le Calvez-Kelm, Egor Prokhortchouk, Nivonirina Robinot, Konstantin G. Skryabin, Magdalena B. Wozniak, Meredith Yeager, Gordana Basta-Jovanovic, Zoran Dzamic, Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Anush Mukeriya, Stefan Rascu, David Zaridze, Vladimir Bencko, Cezary Cybulski, Eleonora Fabianova, Viorel Jinga, Jolanta Lissowska, Jan Lubinski, Marie Navratilova, Peter Rudnai, Neonila Szeszenia-Dabrowska, Simone Benhamou, Geraldine Cancel-Tassin, Olivier Cussenot, Laura Baglietto, Heiner Boeing, Kay-Tee Khaw, Elisabete Weiderpass, Borje Ljungberg, Raviprakash T. Sitaram, Fiona Bruinsma, Susan J. Jordan, Gianluca Severi, Ingrid Winship, Kristian Hveem, Lars J. Vatten, Tony Fletcher, Kvetoslava Koppova, Susanna C. Larsson, Alicja Wolk, Rosamonde E. Banks, Peter J. Selby, Douglas F. Easton, Paul Pharoah, Gabriella Andreotti, Laura E. Beane Freeman, Stella Koutros, Demetrius Albanes, Satu Männistö, Stephanie Weinstein, Peter E. Clark, Todd L. Edwards, Loren Lipworth, Susan M. Gapstur, Victoria L. Stevens, Hallie Carol, Matthew L. Freedman, Mark M. Pomerantz, Eunyoung Cho, Peter Kraft, Mark A. Preston, Kathryn M. Wilson, J. Michael Gaziano, Howard D. Sesso, Amanda Black, Neal D. Freedman, Wen-Yi Huang, John G. Anema, Richard J. Kahnoski, Brian R. Lane, Sabrina L. Noyes, David Petillo, Bin Tean Teh, Ulrike Peters, Emily White, Garnet L. Anderson, Lisa Johnson, Juhua Luo, Julie Buring, I-Min Lee, Wong-Ho Chow, Lee E. Moore, Christopher Wood, Timothy Eisen, Marc Henrion, James Larkin, Poulami Barman, Bradley C. Leibovich, Toni K. Choueiri, G. Mark Lathrop, Nathaniel Rothman, Jean-Francois Deleuze, James D. McKay, Alexander S. Parker, Xifeng Wu, Richard S. Houlston, Paul Brennan, and Stephen J. Chanock
Subjects: Science
Abstract: Risk for renal cell carcinoma (RCC) is higher when there are first-degree family members with the disease. Here, Scelo and colleagues perform a genome-wide association meta-analysis and new genome-wide scan to identify seven new loci with significant RCC association.
Published: 2017
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8. The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study.

Author: Mattias Johansson, Robert Carreras-Torres, Ghislaine Scelo, Mark P Purdue, Daniela Mariosa, David C Muller, Nicolas J Timpson, Philip C Haycock, Kevin M Brown, Zhaoming Wang, Yuanqing Ye, Jonathan N Hofmann, Matthieu Foll, Valerie Gaborieau, Mitchell J Machiela, Leandro M Colli, Peng Li, Jean-Guillaume Garnier, Helene Blanche, Anne Boland, Laurie Burdette, Egor Prokhortchouk, Konstantin G Skryabin, Meredith Yeager, Sanja Radojevic-Skodric, Simona Ognjanovic, Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Anush Mukeriya, Stefan Rascu, David Zaridze, Vladimir Bencko, Cezary Cybulski, Eleonora Fabianova, Viorel Jinga, Jolanta Lissowska, Jan Lubinski, Marie Navratilova, Peter Rudnai, Simone Benhamou, Geraldine Cancel-Tassin, Olivier Cussenot, Elisabete Weiderpass, Börje Ljungberg, Raviprakash Tumkur Sitaram, Christel Häggström, Fiona Bruinsma, Susan J Jordan, Gianluca Severi, Ingrid Winship, Kristian Hveem, Lars J Vatten, Tony Fletcher, Susanna C Larsson, Alicja Wolk, Rosamonde E Banks, Peter J Selby, Douglas F Easton, Gabriella Andreotti, Laura E Beane Freeman, Stella Koutros, Satu Männistö, Stephanie Weinstein, Peter E Clark, Todd L Edwards, Loren Lipworth, Susan M Gapstur, Victoria L Stevens, Hallie Carol, Matthew L Freedman, Mark M Pomerantz, Eunyoung Cho, Kathryn M Wilson, J Michael Gaziano, Howard D Sesso, Neal D Freedman, Alexander S Parker, Jeanette E Eckel-Passow, Wen-Yi Huang, Richard J Kahnoski, Brian R Lane, Sabrina L Noyes, David Petillo, Bin Tean Teh, Ulrike Peters, Emily White, Garnet L Anderson, Lisa Johnson, Juhua Luo, Julie Buring, I-Min Lee, Wong-Ho Chow, Lee E Moore, Timothy Eisen, Marc Henrion, James Larkin, Poulami Barman, Bradley C Leibovich, Toni K Choueiri, G Mark Lathrop, Jean-Francois Deleuze, Marc Gunter, James D McKay, Xifeng Wu, Richard S Houlston, Stephen J Chanock, Caroline Relton, J Brent Richards, Richard M Martin, George Davey Smith, and Paul Brennan
Subjects: Medicine
Abstract: BackgroundSeveral obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findingsGenetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.ConclusionsThis study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
Published: 2019
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9. Lung cancer and socioeconomic status in a pooled analysis of case-control studies.

Author: Jan Hovanec, Jack Siemiatycki, David I Conway, Ann Olsson, Isabelle Stücker, Florence Guida, Karl-Heinz Jöckel, Hermann Pohlabeln, Wolfgang Ahrens, Irene Brüske, Heinz-Erich Wichmann, Per Gustavsson, Dario Consonni, Franco Merletti, Lorenzo Richiardi, Lorenzo Simonato, Cristina Fortes, Marie-Elise Parent, John McLaughlin, Paul Demers, Maria Teresa Landi, Neil Caporaso, Adonina Tardón, David Zaridze, Neonila Szeszenia-Dabrowska, Peter Rudnai, Jolanta Lissowska, Eleonora Fabianova, John Field, Rodica Stanescu Dumitru, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Hans Kromhout, Roel Vermeulen, Paolo Boffetta, Kurt Straif, Joachim Schüz, Benjamin Kendzia, Beate Pesch, Thomas Brüning, and Thomas Behrens
Subjects: Medicine, Science
Abstract: An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study.Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens.The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61-2.09); ESeC OR 1.53 (95% CI 1.44-1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20-1.98); ESeC OR 1.34 (95% CI 1.19-1.52)).SES remained a risk factor for lung cancer after adjustment for smoking behavior.
Published: 2018
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10. Lung cancer among coal miners, ore miners and quarrymen: smoking-adjusted risk estimates from the synergy pooled analysis of case–control studies

Author: Dirk Taeger, Beate Pesch, Benjamin Kendzia, Thomas Behrens, Karl-Heinz Jöckel, Dirk Dahmann, Jack Siemiatycki, Hans Kromhout, Roel Vermeulen, Susan Peters, Ann Olsson, Irene Brüske, Heinz-Erich Wichmann, Isabelle Stücker, Florence Guida, Adonina Tardón, Franco Merletti, Dario Mirabelli, Lorenzo Richiardi, Hermann Pohlabeln, Wolfgang Ahrens, Maria Teresa Landi, Neil Caporaso, Angela Cecilia Pesatori, Anush Mukeriya, Neonila Szeszenia-Dabrowska, Jolanta Lissowska, Per Gustavsson, John Field, Michael W Marcus, Eleonora Fabianova, Andrea ’t Mannetje, Neil Pearce, Peter Rudnai, Vladimir Bencko, Vladimir Janout, Rodica Stanescu Dumitru, Lenka Foretova, Francesco Forastiere, John McLaughlin, Paul Demers Paul Demers, Bas Bueno-de-Mesquita, Joachim Schüz, Kurt Straif, and Thomas Brüning
Subjects: coal mining, histological subtype, ore mining, ore miner, cancer, smoking, lung cancer, mining, risk estimate, population-based study, coal miner, case–control study, pooled analysis, quarrymen, Public aspects of medicine, RA1-1270
Abstract: OBJECTIVES: Working in mines and quarries has been associated with an elevated lung cancer risk but with inconsistent results for coal miners. This study aimed to estimate the smoking-adjusted lung cancer risk among coal miners and compare the risk pattern with lung cancer risks among ore miners and quarrymen. METHODS: We estimated lung cancer risks of coal and ore miners and quarrymen among 14 251 lung cancer cases and 17 267 controls from the SYNERGY pooled case–control study, controlling for smoking and employment in other at-risk occupations. RESULTS: Ever working as miner or quarryman (690 cases, 436 controls) was associated with an elevated odds ratio (OR) of 1.55 [95% confidence interval (95% CI) 1.34–1.79] for lung cancer. Ore miners (53 cases, 24 controls) had a higher OR (2.34, 95% CI 1.36-4.03) than quarrymen (67 cases, 39 controls; OR 1.92, 95% CI 1.21–3.05) and coal miners (442 cases, 297 controls; OR 1.40, 95% CI 1.18–1.67), but CI overlapped. We did not observe trends by duration of exposure or time since last exposure. CONCLUSIONS: This pooled analysis of population-based studies demonstrated an excess lung cancer risk among miners and quarrymen that remained increased after adjustment for detailed smoking history and working in other at-risk occupations. The increase in risk among coal miners were less pronounced than for ore miners or quarrymen.
Published: 2015
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11. The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract.

Author: Manon Delahaye-Sourdeix, Javier Oliver, Maria N Timofeeva, Valérie Gaborieau, Mattias Johansson, Amélie Chabrier, Magdalena B Wozniak, Darren R Brenner, Maxime P Vallée, Devasena Anantharaman, Pagona Lagiou, Ivana Holcátová, Lorenzo Richiardi, Kristina Kjaerheim, Antonio Agudo, Xavier Castellsagué, Tatiana V Macfarlane, Luigi Barzan, Cristina Canova, Nalin S Thakker, David I Conway, Ariana Znaor, Claire M Healy, Wolfgang Ahrens, David Zaridze, Neonilia Szeszenia-Dabrowska, Jolanta Lissowska, Eleonora Fabianova, Ioan Nicolae Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Maria Paula Curado, Sergio Koifman, Ana Menezes, Victor Wünsch-Filho, José Eluf-Neto, Paolo Boffetta, Leticia Fernández Garrote, Diego Serraino, Marcin Lener, Ewa Jaworowska, Jan Lubiński, Stefania Boccia, Thangarajan Rajkumar, Tanuja A Samant, Manoj B Mahimkar, Keitaro Matsuo, Silvia Franceschi, Graham Byrnes, Paul Brennan, and James D McKay
Subjects: Medicine, Science
Abstract: Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.
Published: 2015
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12. Supplementary Tables 1-3 from A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers

Author: James D. McKay, Paul Brennan, Paolo Boffetta, Richard B. Hayes, Mia Hashibe, Stefania Boccia, Leticia Fernandez, José Eluf-Neto, Victor Wünsch-Filho, Ana Menezes, Sergio Koifman, Maria Paula Curado, Vladimir Janout, Lenka Foretova, Vladimir Bencko, Alexandru Bucur, Eleonora Fabianova, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, David Zaridze, Wolfgang Ahrens, Claire M. Healy, Ariana Znaor, David I. Conway, Nalin S. Thakker, Cristina Canova, Luigi Barzan, Tatiana V. Macfarlane, Xavier Castellsagué, Antonio Agudo, Kristina Kjaerheim, Lorenzo Richiardi, Ivana Holcátová, Pagona Lagiou, Simone Benhamou, Chu Chen, Stephen M. Schwartz, Renyi Wang, Shen-Chih Chang, Zuo-Feng Zhang, Erich M. Sturgis, Qingyi Wei, Philip Lazarus, Joshua E. Muscat, Marcin Lener, Joanna Trubicka, Jan Lubiński, Wilbert H. M. Peters, Johannes J. Manni, Martin Lacko, Michael D. McClean, Brock Christensen, Karl T. Kelsey, Renato Talamini, Rolando Herrero, Silvia Franceschi, Tomoko Nukui, Shama Buch, Marjorie Romkes, Jingchun Luo, Mark C. Weissler, Andrew F. Olshan, Shu-chun Chuang, Amelie Chabrier, Graham Byrnes, Valerie Gaborieau, Therese Truong, and Dan Chen
Abstract: Supplementary Tables 1-3 from A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers
Published: 2023

13. Supplementary Tables S1-S6 from Effect of Occupational Exposures on Lung Cancer Susceptibility: A Study of Gene–Environment Interaction Analysis

Author: Paolo Boffetta, Vladimir Janout, Lenka Foretova, Isabelle Stücker, Valerie Gaborieau, Vladimir Bencko, Dana Mates, Eleonora Fabianova, Jolanta Lissowska, Peter Rudnai, Beata Świątkowska, Neonila Szeszenia-Dabrowska, David Zaridze, Paul Brennan, Samantha Sartori, and Jyoti Malhotra
Abstract: Supplementary Tables S1-S6. Table S1. Number and percentage of cases and control with exposure to each occupational agent. Table S2. SNP-level significant occupational exposure interactions for known occupational lung carcinogens. Table S3. SNP-level significant occupational exposure interactions for occupational exposures with increased risk for lung cancer not clear. Table S4. Gene-level significant occupational exposure interactions for occupational exposures with increased risk for lung cancer not clear. Table S5. Significant genomic regions for occupational exposure interactions and the significant genes identified in these regions. Table S6. Main categories of proteins coded by the significant genes identified by the gene-occupational interaction analyses.
Published: 2023

14. Data from Effect of Occupational Exposures on Lung Cancer Susceptibility: A Study of Gene–Environment Interaction Analysis

Author: Paolo Boffetta, Vladimir Janout, Lenka Foretova, Isabelle Stücker, Valerie Gaborieau, Vladimir Bencko, Dana Mates, Eleonora Fabianova, Jolanta Lissowska, Peter Rudnai, Beata Świątkowska, Neonila Szeszenia-Dabrowska, David Zaridze, Paul Brennan, Samantha Sartori, and Jyoti Malhotra
Abstract: Background: Occupational exposures are known risk factors for lung cancer. Role of genetically determined host factors in occupational exposure–related lung cancer is unclear.Methods: We used genome-wide association (GWA) data from a case–control study conducted in 6 European countries from 1998 to 2002 to identify gene–occupation interactions and related pathways for lung cancer risk. GWA analysis was performed for each exposure using logistic regression and interaction term for genotypes, and exposure was included in this model. Both SNP-based and gene-based interaction P values were calculated. Pathway analysis was performed using three complementary methods, and analyses were adjusted for multiple comparisons. We analyzed 312,605 SNPs and occupational exposure to 70 agents from 1,802 lung cancer cases and 1,725 cancer-free controls.Results: Mean age of study participants was 60.1 ± 9.1 years and 75% were male. Largest number of significant associations (P ≤ 1 × 10−5) at SNP level was demonstrated for nickel, brick dust, concrete dust, and cement dust, and for brick dust and cement dust at the gene-level (P ≤ 1 × 10−4). Approximately 14 occupational exposures showed significant gene–occupation interactions with pathways related to response to environmental information processing via signal transduction (P < 0.001 and FDR < 0.05). Other pathways that showed significant enrichment were related to immune processes and xenobiotic metabolism.Conclusion: Our findings suggest that pathways related to signal transduction, immune process, and xenobiotic metabolism may be involved in occupational exposure–related lung carcinogenesis.Impact: Our study exemplifies an integrative approach using pathway-based analysis to demonstrate the role of genetic variants in occupational exposure–related lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 24(3); 570–9. ©2015 AACR.
Published: 2023

15. Data from A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers

Author: James D. McKay, Paul Brennan, Paolo Boffetta, Richard B. Hayes, Mia Hashibe, Stefania Boccia, Leticia Fernandez, José Eluf-Neto, Victor Wünsch-Filho, Ana Menezes, Sergio Koifman, Maria Paula Curado, Vladimir Janout, Lenka Foretova, Vladimir Bencko, Alexandru Bucur, Eleonora Fabianova, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, David Zaridze, Wolfgang Ahrens, Claire M. Healy, Ariana Znaor, David I. Conway, Nalin S. Thakker, Cristina Canova, Luigi Barzan, Tatiana V. Macfarlane, Xavier Castellsagué, Antonio Agudo, Kristina Kjaerheim, Lorenzo Richiardi, Ivana Holcátová, Pagona Lagiou, Simone Benhamou, Chu Chen, Stephen M. Schwartz, Renyi Wang, Shen-Chih Chang, Zuo-Feng Zhang, Erich M. Sturgis, Qingyi Wei, Philip Lazarus, Joshua E. Muscat, Marcin Lener, Joanna Trubicka, Jan Lubiński, Wilbert H. M. Peters, Johannes J. Manni, Martin Lacko, Michael D. McClean, Brock Christensen, Karl T. Kelsey, Renato Talamini, Rolando Herrero, Silvia Franceschi, Tomoko Nukui, Shama Buch, Marjorie Romkes, Jingchun Luo, Mark C. Weissler, Andrew F. Olshan, Shu-chun Chuang, Amelie Chabrier, Graham Byrnes, Valerie Gaborieau, Therese Truong, and Dan Chen
Abstract: Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35).Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case–control studies.Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08–1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95–1.09, P = 0.66; P-heterogeneity (Phet) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12–1.34, P = 7 × 10−6) but not males (OR = 1.02, 95% CI = 0.97–1.08, P = 0.35; Phet = 6 × 10−4). There was little evidence for a sexdifference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (Phet = 0.86).Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers.Impact: Further research is warranted to elucidate the mechanisms underlying these observations. Cancer Epidemiol Biomarkers Prev; 20(4); 658–64. ©2011 AACR.
Published: 2023

16. Supplementary Table 2 from No Causal Association Identified for Human Papillomavirus Infections in Lung Cancer

Author: Paul Brennan, Massimo Tommasino, Ghislaine Scelo, Michael Pawlita, Mattias Johansson, Elisabete Weiderpass, Françoise Clavel-Chapelon, Anastasia Kotanidou, H. Bas Bueno-de-Mesquita, Vittorio Krogh, Mikael Johansson, J. Ramón Quirós, Heiner Boeing, Ruth C. Travis, Anne Tjønneland, Eleonora Fabianova, Peter Rudnai, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Dana Mates, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, Anush Mukeria, David Zaridze, Sandrine McKay-Chopin, Behnoush Abedi-Ardekani, Christine Carreira, Gordana Halec, Tim Waterboer, Tarik Gheit, and Devasena Anantharaman
Abstract: PDF file - 67KB, Antibodies to type-specific HPV proteins and the risk of lung cancer.
Published: 2023

17. Data from No Causal Association Identified for Human Papillomavirus Infections in Lung Cancer

Author: Paul Brennan, Massimo Tommasino, Ghislaine Scelo, Michael Pawlita, Mattias Johansson, Elisabete Weiderpass, Françoise Clavel-Chapelon, Anastasia Kotanidou, H. Bas Bueno-de-Mesquita, Vittorio Krogh, Mikael Johansson, J. Ramón Quirós, Heiner Boeing, Ruth C. Travis, Anne Tjønneland, Eleonora Fabianova, Peter Rudnai, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Dana Mates, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, Anush Mukeria, David Zaridze, Sandrine McKay-Chopin, Behnoush Abedi-Ardekani, Christine Carreira, Gordana Halec, Tim Waterboer, Tarik Gheit, and Devasena Anantharaman
Abstract: Human papillomavirus (HPV) infections have been implicated in lung carcinogenesis, but causal associations remain uncertain. We evaluated a potential causal role for HPV infections in lung cancer through an analysis involving serology, tumor DNA, RNA, and p16 protein expression. Association between type-specific HPV antibodies and risk of lung cancer was examined among 3,083 cases and 4,328 controls in two case–control studies (retrospective) and one nested case–control study (prospective design). Three hundred and thirty-four available tumors were subjected to pathologic evaluation and subsequent HPV genotyping following stringent conditions to detect all high-risk and two low-risk HPV types. All HPV DNA-positive tumors were further tested for the expression of p16 protein and type-specific HPV mRNA. On the basis of the consistency of the results, although HPV11 and HPV31 E6 antibodies were associated with lung cancer risk in the retrospective study, no association was observed in the prospective design. Presence of type-specific antibodies correlated poorly with the presence of the corresponding HPV DNA in the tumor. Although nearly 10% of the lung tumors were positive for any HPV DNA (7% for HPV16 DNA), none expressed the viral oncogenes. No association was observed between HPV antibodies or DNA and lung cancer survival. In conclusion, we found no supportive evidence for the hypothesized causal association between HPV infections and lung cancer. Cancer Res; 74(13); 3525–34. ©2014 AACR.
Published: 2023

18. Supplementary Table 1 from No Causal Association Identified for Human Papillomavirus Infections in Lung Cancer

Author: Paul Brennan, Massimo Tommasino, Ghislaine Scelo, Michael Pawlita, Mattias Johansson, Elisabete Weiderpass, Françoise Clavel-Chapelon, Anastasia Kotanidou, H. Bas Bueno-de-Mesquita, Vittorio Krogh, Mikael Johansson, J. Ramón Quirós, Heiner Boeing, Ruth C. Travis, Anne Tjønneland, Eleonora Fabianova, Peter Rudnai, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Dana Mates, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, Anush Mukeria, David Zaridze, Sandrine McKay-Chopin, Behnoush Abedi-Ardekani, Christine Carreira, Gordana Halec, Tim Waterboer, Tarik Gheit, and Devasena Anantharaman
Abstract: PDF file - 55KB, Association between type-specific HPV antibodies and risk of lung cancer by seropositivity threshold.
Published: 2023

19. Supplementary Table 3 from No Causal Association Identified for Human Papillomavirus Infections in Lung Cancer

Author: Paul Brennan, Massimo Tommasino, Ghislaine Scelo, Michael Pawlita, Mattias Johansson, Elisabete Weiderpass, Françoise Clavel-Chapelon, Anastasia Kotanidou, H. Bas Bueno-de-Mesquita, Vittorio Krogh, Mikael Johansson, J. Ramón Quirós, Heiner Boeing, Ruth C. Travis, Anne Tjønneland, Eleonora Fabianova, Peter Rudnai, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Dana Mates, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, Anush Mukeria, David Zaridze, Sandrine McKay-Chopin, Behnoush Abedi-Ardekani, Christine Carreira, Gordana Halec, Tim Waterboer, Tarik Gheit, and Devasena Anantharaman
Abstract: PDF file - 52KB, Comparison of HPV16 DNA positivity by sex, smoking status and lung histology.
Published: 2023

20. Author response for 'Risk factors for head and neck cancer in more and less developed countries: Analysis from the INHANCE Consortium'

Author: null Neerav Goyal, null Max Hennessy, null Erik Lehman, null Wenxue Lin, null Antonio Agudo, null Wolfgang Ahrens, null Stefania Boccia, null Paul Brennan, null Hermann Brenner, null Gabriella Cadoni, null Cristina Canova, null Chu Chen, null David Conway, null Maria Paula Curado, null Luigino Dal Maso, null Alexander W. Daudt, null Valeria Edefonti, null Eleonora Fabianova, null Leticia Fernandez, null Silvia Franceschi, null Werner Garavello, null Maura Gillison, null Richard B. Hayes, null Claire Healy, null Rolando Herrero, null Ivana Holcatova, null Jossy L. Kanda, null Karl Kelsey, null Bo T Hansen, null Rosalina Koifman, null Pagona Lagiou, null Carlo La Vecchia, null Fabio Levi, null Guojun Li, null Jolanta Lissowska, null Rossana Mendoza López, null Danièle Luce, null Gary Macfarlane, null Dana Mates, null Keitaro Matsuo, null Michael McClean, null Ana Menezes, null Gwenn Menvielle, null Hal Morgenstern, null Kirsten Moysich, null Eva Negri, null Andrew F. Olshan, null Tamas Pandics, null Jerry Polesel, null Mark Purdue, null Loredana Radoi, null Heribert Ramroth, null Lorenzo Richiardi, null Stimson Schantz, null Stephen M. Schwartz, null Diego Serraino, null Oxana Shangina, null Elaine Smith, null Erich M. Sturgis, null Beata Świątkowska, null Peter Thomson, null Thomas L. Vaughan, null Marta Vilensky, null Deborah M. Winn, null Victor Wunsch‐Filho, null Guo‐Pei Yu, null Jose P. Zevallos, null Zuo‐Feng Zhang, null Tongzhang Zheng, null Ariana Znaor, null Paolo Boffetta, null Mia Hashibe, null Yuan‐Chin Amy Lee, and null Joshua E Muscat
Published: 2022

21. Risk factors for head and neck cancer in more and less developed countries: Analysis from the INHANCE consortium

Author: Neerav Goyal, Max Hennessy, Erik Lehman, Wenxue Lin, Antonio Agudo, Wolfgang Ahrens, Stefania Boccia, Paul Brennan, Hermann Brenner, Gabriella Cadoni, Cristina Canova, Chu Chen, David Conway, Maria Paula Curado, Luigino Dal Maso, Alexander W. Daudt, Valeria Edefonti, Eleonora Fabianova, Leticia Fernandez, Silvia Franceschi, Werner Garavello, Maura Gillison, Richard B. Hayes, Claire Healy, Rolando Herrero, Ivana Holcatova, Jossy L. Kanda, Karl Kelsey, Bo T. Hansen, Rosalina Koifman, Pagona Lagiou, Carlo La Vecchia, Fabio Levi, Guojun Li, Jolanta Lissowska, Rossana Mendoza López, Danièle Luce, Gary Macfarlane, Dana Mates, Keitaro Matsuo, Michael McClean, Ana Menezes, Gwenn Menvielle, Hal Morgenstern, Kirsten Moysich, Eva Negri, Andrew F. Olshan, Tamas Pandics, Jerry Polesel, Mark Purdue, Loredana Radoi, Heribert Ramroth, Lorenzo Richiardi, Stimson Schantz, Stephen M. Schwartz, Diego Serraino, Oxana Shangina, Elaine Smith, Erich M. Sturgis, Beata Świątkowska, Peter Thomson, Thomas L. Vaughan, Marta Vilensky, Deborah M. Winn, Victor Wunsch‐Filho, Guo‐Pei Yu, Jose P. Zevallos, Zuo‐Feng Zhang, Tongzhang Zheng, Ariana Znaor, Paolo Boffetta, Mia Hashibe, Yuan‐Chin A. Lee, Joshua E. Muscat, Pennsylvania State University (Penn State), Penn State System, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Glasgow, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Bologna/Università di Bologna, University of Utah School of Medicine [Salt Lake City], This work was supported by the European Community (5th Framework Programme) grant no QLK1-CT-2001-00182, INHANCE Pooled Data Project: NCI R03CA113157NIDCR R03DE016611 and the Intramural Program of the NCI, NIH, United States. Individual studies were supported by: Aviano study: Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research, Baltimore study: NIH [DE016631], Boston study: NIH [R01CA078609, R01CA100679], Central Europe study: World Cancer Research Fund and the European Commission INCO-COPERNICUS Program [Contract No. IC15- CT98-0332], France 2001–2007 (ICARE): French National Research Agency (ANR), French National Cancer Institute (INCA), French Agency for Food, Environmental and Occupational Health and Safety (ANSES), French Institute for Public Health Surveillance (InVS), Fondation pour la Recherche Médicale (FRM), Fondation de France, Fondation ARC pour la Recherche sur le Cancer, French Ministry of Labour (Direction Générale du Travail), French Ministry of Health (Direction Générale de la Santé), Germany-Heidelberg study: grant No. 01GB9702/3 from the German Ministry of Education and Research, IARC Multicenter study: Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government [FIS 97/0024, FIS 97/0662, BAE 01/5013], International Union Against Cancer (UICC), and Yamagiwa-Yoshida Memorial International Cancer Study Grant, Iowa study: NIH [NIDCR R01DE011979, NIDCR R01DE013110, NIH FIRCA TW001500] and Veterans Affairs Merit Review Funds, Italy multicenter study: Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research, Japan study (2001–2005): Scientific Research grant from the Ministry of Education, Science, Sports, Culture and Technology of Japan (17015052) and grant for the Third-Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan (H20-002), Latin America study: Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundaco de Amparo a` Pesquisa no Estado de Sao Paulo (FAPESP) [No 01/01768-2, 04/12054-9, 10/51168-0], and European Commission [IC18-CT97-0222], Los Angeles Study: NIH [P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667] and the Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center, MSKCC study: NIH [R01CA051845], Northeast US study: NIH R01DE013158, North Carolina Study: NIH [R01CA061188], & NIEHS [P30ES010126], NY multicenter study: NIH [P01CA068384 K07CA104231], Milan study: Italian Association for Research on Cancer (AIRC), Puerto Rico study: jointly funded by National Institutes of Health (NCI) US and NIDCR intramural programs, Rome study: AIRC (Italian Agency for Research on Cancer), Saarland study: Ministry of Science, Research and Arts Baden-Wurttemberg, Seattle study: NIH [R01CA048996, R01DE012609], Seattle-LEO study: NIH [R01CA030022., and ANR-05-SEST-0033,ICARE,Facteurs de risques professionnels des cancers du poumon et des voies aéro-digestives supérieures Etude ICARE (Investigations sur les Cancers Respiratoires et l'Environnement professionnel)(2005)
Subjects: socioeconomic status, head and neck, INHANCE, Otorhinolaryngology, alcohol use, head and neck cancer, smoking, [SDV.CAN]Life Sciences [q-bio]/Cancer, Settore MED/31 - OTORINOLARINGOIATRIA, General Dentistry
Abstract: Objective:\ud We analyzed the pooled case-control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries.\ud \ud Subjects and Methods:\ud The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared.\ud \ud Results:\ud The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20 years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20 years conferred a higher risk for oropharynx, hypopharynx, and larynx cancer in less developed countries. The proportion of cases that were young (
Published: 2022

22. Application of two job indices for general occupational demands in a pooled analysis of case–control studies on lung cancer

Author: Neil E. Caporaso, Ann Olsson, Dana Mates, Cristina Fortes, Tamás Pándics, Simonato Lorenzo, Jolanta Lissowska, Kurt Straif, Beate Pesch, Jan Hovanec, Guillermo Fernández-Tardón, Hans Kromhout, Pascal Guénel, Karl-Heinz Jöckel, Eleonora Fabianova, Roel Vermeulen, Wolfgang Ahrens, Stefan Karrasch, Hermann Pohlabeln, John K. Field, Joachim Schüz, Vladimir Bencko, Beata Świątkowska, Thomas Brüning, Dario Consonni, Danièle Luce, Thomas Behrens, Maria Teresa Landi, David I. Conway, John R. McLaughlin, Per Gustavsson, Paolo Boffetta, Marie-Élise Parent, Vladimir Janout, Franco Merletti, Lorenzo Richiardi, Lenka Foretova, Heinz-Erich Wichmann, David Zaridze, Swaantje Casjens, Paul A. Demers, Jack Siemiatycki, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Ruhr-Universität Bochum [Bochum], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), University of Glasgow, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Ruhrlandklinik University Hospital, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Universität Bremen, Helmholtz Zentrum München = German Research Center for Environmental Health, Ludwig-Maximilians-Universität München (LMU), Karolinska Institute, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli studi di Torino = University of Turin (UNITO), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Toronto, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Universidad de Oviedo [Oviedo], CIBER de Epidemiología y Salud Pública (CIBERESP), N.N. Blokhin National Medical Research Center of Oncology, Nofer Institute of Occupational Medicine (NIOM), National Public Health Centre, Medical University of Warsaw - Poland, University of Liverpool, National Institute of Public Health [Romania] (INSP), Charles University [Prague] (CU), Masaryk Memorial Cancer Institute (MMCI), Palacky University Olomouc, Universiteit Utrecht, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Stony Brook University [SUNY] (SBU), State University of New York (SUNY), German Social Accident Insurance [FP 271], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Helmholtz-Zentrum München (HZM), University of Turin, University Hospital of Padua, Masaryk Memorial Cancer Institute (RECAMO), Chard-Hutchinson, Xavier, Hovanec J., Siemiatycki J., Conway D.I., Olsson A., Guenel P., Luce D., Jockel K.-H., Pohlabeln H., Ahrens W., Karrasch S., Wichmann H.-E., Gustavsson P., Consonni D., Merletti F., Richiardi L., Simonato L., Fortes C., Parent M.-E., McLaughlin J.R., Demers P., Landi M.T., Caporaso N., Fernandez-Tardon G., Zaridze D., Swiatkowska B., Pandics T., Lissowska J., Fabianova E., Field J.K., Mates D., Bencko V., Foretova L., Janout V., Kromhout H., Vermeulen R., Boffetta P., Straif K., Schuz J., Casjens S., Pesch B., Bruning T., and Behrens T.
Subjects: Male, Lung Neoplasms, Occupational prestige, Short Communication, [SDV]Life Sciences [q-bio], Medizin, Logistic regression, 03 medical and health sciences, occupational demand, 0302 clinical medicine, Occupational Exposure, medicine, Odds Ratio, case–control, Humans, cancer, Risk factor, Occupations, Lung cancer, job index, business.industry, Environmental and Occupational Health, Smoking, Public Health, Environmental and Occupational Health, Cancer, Odds ratio, Social prestige, medicine.disease, 030210 environmental & occupational health, Confidence interval, Key terms job index, [SDV] Life Sciences [q-bio], lung cancer, Tumor subtype, Case-Control Studies, Female, Public Health, Public aspects of medicine, RA1-1270, business, Psychosocial, Tumor Subtype, Job index, Social Prestige, Demography
Abstract: The German Social Accident Insurance supported this study (grant number FP 271)., Hovanec J, Siemiatycki J, Conway DI, Olsson A, Guenel P, Luce D, Jöckel KH, Pohlabeln H, Ahrens W, Karrasch S, Wichmann HE, Gustavsson P, Consonni D, Merletti F, Richiardi L, Lorenzo S, Fortes C, Parent MÉ, McLaughlin JR, Demers P, Landi MT, Caporaso N, Fernández-Tardón G, Zaridze D, Świątkowska B, Pándics T, Lissowska J, Fabianova E, Field JK, Mates D, Bencko V, Foretova L, Janout V, Kromhout H, Vermeulen R, Boffetta P, Straif K, Schüz J, Casjens S, Pesch B, Brüning T, Behrens T.
Published: 2021

23. Gallbladder disease, cholecystectomy, and pancreatic cancer risk in the International Pancreatic Cancer Case-Control Consortium (PanC4)

Author: Valentina Rosato, Eva Negri, Cristina Bosetti, Núria Malats, Paulina Gomez-Rubio, PanGenEU Consortium, Patrick Maisonneuve, Anthony B. Miller, H. Bas Bueno-de-Mesquita, Peter A. Baghurst, Witold Zatonski, Gloria M. Petersen, Ghislaine Scelo, Ivana Holcatova, Eleonora Fabianova, Diego Serraino, Sara H. Olson, Jesús Vioque, Pagona Lagiou, Eric J. Duell, Paolo Boffetta, Carlo La Vecchia, V. Rosato, E. Negri, C. Bosetti, N. Malat, P. Gomez-Rubio, Consortium PanGenEU, P. Maisonneuve, A. B. Miller, H. B. Bueno-de-Mesquita, P. A. Baghurst, W. Zatonski, G. M. Petersen, G. Scelo, I. Holcatova, E. Fabianova, D. Serraino, S. H. Olson, J. Vioque, P. Lagiou, E. J. Duell, P. Boffetta, and C. La Vecchia
Subjects: Male, Cancer Research, medicine.medical_specialty, Epidemiology, medicine.medical_treatment, Gallbladder disease, pancreatic cancer, Gallbladder Diseases, cholecystectomy, Gastroenterology, risks factors, 03 medical and health sciences, 0302 clinical medicine, gallbladder disease, Risk Factors, Internal medicine, Pancreatic cancer, Humans, Medicine, risk factors, pooled analysi, Cholecystectomy, Medical history, 030212 general & internal medicine, Aged, case-control-studie, business.industry, case-control studies, Public Health, Environmental and Occupational Health, Case-control study, International Agencies, Odds ratio, Middle Aged, Prognosis, medicine.disease, Confidence interval, Pancreatic Neoplasms, Oncology, Case-Control Studies, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, pooled analysis, business
Abstract: BACKGROUND: The association among gallbladder disease, cholecystectomy, and pancreatic cancer is unclear. Moreover, time interval between gallbladder disease or cholecystectomy and pancreatic cancer diagnosis is not considered in most previous studies. AIM: To quantify the association among gallbladder disease, cholecystectomy, and pancreatic cancer, considering time since first diagnosis of gallbladder disease or cholecystectomy. METHODS: We used data from nine case-control studies within the Pancreatic Cancer Case-Control Consortium, including 5760 cases of adenocarcinoma of the exocrine pancreas and 8437 controls. We estimated pooled odds ratios and the corresponding 95% confidence intervals by estimating study-specific odds ratios through multivariable unconditional logistic regression models, and then pooling the obtained estimates using fixed-effects models. RESULTS: Compared with patients with no history of gallbladder disease, the pooled odds ratio of pancreatic cancer was 1.69 (95% confidence interval, 1.51-1.88) for patients reporting a history of gallbladder disease. The odds ratio was 4.90 (95% confidence interval, 3.45-6.97) for gallbladder disease diagnosed
Published: 2020

24. A Plasma-Derived Protein-Metabolite Multiplexed Panel for Early-Stage Pancreatic Cancer

Author: Anirban Maitra, Jody Vykoukal, C. Max Schmidt, Paul Brennan, Eleonora Fabianova, Jennifer B. Dennison, Ivana Holcatova, Michele T. Yip-Schneider, Ghislaine Scelo, Samir M. Hanash, Ayumu Taguchi, Ziding Feng, Nikul Patel, Vladimir Janout, Michela Capello, Lenka Foretova, Johannes F. Fahrmann, Deepali L. Kundnani, Randall E. Brand, Eunice Murage, Leonidas E. Bantis, and Jianjun Zhang
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Metabolite, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Pancreatic cancer, Biomarkers, Tumor, medicine, Humans, Neoplasm Invasiveness, Stage (cooking), Neoplasm Staging, Intraductal papillary mucinous neoplasm, Plasma derived, business.industry, Articles, medicine.disease, Adenocarcinoma, Mucinous, Carcinoma, Papillary, Confidence interval, 3. Good health, Pancreatic Neoplasms, chemistry, LRG1, Case-Control Studies, 030220 oncology & carcinogenesis, Metabolome, Pancreatic cysts, Transcriptome, business, Carcinoma, Pancreatic Ductal, Follow-Up Studies
Abstract: Background We applied a training and testing approach to develop and validate a plasma metabolite panel for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC) alone and in combination with a previously validated protein panel for early-stage PDAC. Methods A comprehensive metabolomics platform was initially applied to plasmas collected from 20 PDAC cases and 80 controls. Candidate markers were filtered based on a second independent cohort that included nine invasive intraductal papillary mucinous neoplasm cases and 51 benign pancreatic cysts. Blinded validation of the resulting metabolite panel was performed in an independent test cohort consisting of 39 resectable PDAC cases and 82 matched healthy controls. The additive value of combining the metabolite panel with a previously validated protein panel was evaluated. Results Five metabolites (acetylspermidine, diacetylspermine, an indole-derivative, and two lysophosphatidylcholines) were selected as a panel based on filtering criteria. A combination rule was developed for distinguishing between PDAC and healthy controls using the Training Set. In the blinded validation study with early-stage PDAC samples and controls, the five metabolites yielded areas under the curve (AUCs) ranging from 0.726 to 0.842, and the combined metabolite model yielded an AUC of 0.892 (95% confidence interval [CI] = 0.828 to 0.956). Performance was further statistically significantly improved by combining the metabolite panel with a previously validated protein marker panel consisting of CA 19–9, LRG1, and TIMP1 (AUC = 0.924, 95% CI = 0.864 to 0.983, comparison DeLong test one-sided P= .02). Conclusions A metabolite panel in combination with CA19-9, TIMP1, and LRG1 exhibited substantially improved performance in the detection of early-stage PDAC compared with a protein panel alone.
Published: 2018

25. Genetic Contributions to The Association Between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis

Author: Luigi Barzan, Vladimir Janout, Anna Puggina, Kristina Kjærheim, James McKay, Valerie Gaborieau, Paul Brennan, Pagona Lagiou, Jolanta Lissowska, Antonio Agudo, Cristina Canova, Ioan Nicolae Mates, David I. Conway, Ivana Holcatova, Xavier Castellsagué, Lorenzo Richiardi, Eleonora Fabianova, Ariana Znaor, Vladimir Bencko, Lenka Foretova, Nalin Thakker, Wolfgang Ahrens, Neonilia Szeszenia-Dabrowska, Stefania Boccia, Tatiana V. Macfarlane, Claire M. Healy, Roberta Pastorino, David Zaridze, Robert Carreras-Torres, and Nofer Institute of Occupational Medicine
Subjects: 0301 basic medicine, Oncology, Male, lcsh:Medicine, 0302 clinical medicine, risk factors, lcsh:Science, Multidisciplinary, Confounding, Mendelian Randomization Analysis, Middle Aged, 3. Good health, Creixement humà, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Female, cancer epidemiology, medicine.medical_specialty, Single-nucleotide polymorphism, Cancer epidemiology, Risk factors, Human growth, Polymorphism, Single Nucleotide, Article, POOLED ANALYSIS, EPIDEMIOLOGY CONSORTIUM, 03 medical and health sciences, Internal medicine, Mendelian randomization, medicine, Genetic predisposition, Genetics, Humans, Genetic Predisposition to Disease, Settore MED/42 - IGIENE GENERALE E APPLICATA, Genetic association, Aged, business.industry, lcsh:R, Odds ratio, Neck cancer, Confidence interval, Body Height, Càncer de coll, 030104 developmental biology, PROSPECTIVE COHORT, Case-Control Studies, RISK-FACTORS, lcsh:Q, business, Genètica, Genome-Wide Association Study
Abstract: With the aim to dissect the effect of adult height on head and neck cancer (HNC), we use the Mendelian randomization (MR) approach to test the association between genetic instruments for height and the risk of HNC. 599 single nucleotide polymorphisms (SNPs) were identified as genetic instruments for height, accounting for 16% of the phenotypic variation. Genetic data concerning HNC cases and controls were obtained from a genome-wide association study. Summary statistics for genetic association were used in complementary MR approaches: the weighted genetic risk score (GRS) and the inverse-variance weighted (IVW). MR-Egger regression was used for sensitivity analysis and pleiotropy evaluation. From the GRS analysis, one standard deviation (SD) higher height (6.9 cm; due to genetic predisposition across 599 SNPs) raised the risk for HNC (Odds ratio (OR), 1.14; 95% Confidence Interval (95%CI), 0.99–1.32). The association analyses with potential confounders revealed that the GRS was associated with tobacco smoking (OR = 0.80, 95% CI (0.69–0.93)). MR-Egger regression did not provide evidence of overall directional pleiotropy. Our study indicates that height is potentially associated with HNC risk. However, the reported risk could be underestimated since, at the genetic level, height emerged to be inversely associated with smoking.
Published: 2018

26. KRASmutations in blood circulating cell-free DNA: a pancreatic cancer case-control

Author: Maroulio Pertesi, Florence Le Calvez-Kelm, Maxime Vallée, Ghislaine Scelo, Tiffany M. Delhomme, Matthieu Foll, Sabina Rinaldi, Zora Adamcakova, Priscilia Chopard, Paul Brennan, Lenka Foretova, James McKay, Eleonora Fabianova, Vladimir Janout, Magdalena B. Wozniak, Ivana Holcatova, Graham Byrnes, and Geoffroy Durand
Subjects: Male, 0301 basic medicine, KRAS mutations, Slovakia, CA-19-9 Antigen, DNA Mutational Analysis, Mutant, pancreatic cancer detection, Pilot Projects, medicine.disease_cause, Deep sequencing, Circulating Tumor DNA, cell-free DNA, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Predictive Value of Tests, Pancreatic cancer, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Allele, plasma, Aged, Czech Republic, Neoplasm Staging, business.industry, Reproducibility of Results, Middle Aged, Amplicon, medicine.disease, Pancreatic Neoplasms, Phenotype, 030104 developmental biology, Oncology, Cell-free fetal DNA, Case-Control Studies, 030220 oncology & carcinogenesis, Mutation, Immunology, Cancer research, Pancreatitis, Female, KRAS, business, Research Paper, Carcinoma, Pancreatic Ductal
Abstract: The utility of KRAS mutations in plasma circulating cell-free DNA (cfDNA) samples as non-invasive biomarkers for the detection of pancreatic cancer has never been evaluated in a large case-control series. We applied a KRAS amplicon-based deep sequencing strategy combined with analytical pipeline specifically designed for the detection of low-abundance mutations to screen plasma samples of 437 pancreatic cancer cases, 141 chronic pancreatitis subjects, and 394 healthy controls. We detected mutations in 21.1% (N=92) of cases, of whom 82 (89.1%) carried at least one mutation at hotspot codons 12, 13 or 61, with mutant allelic fractions from 0.08% to 79%. Advanced stages were associated with an increased proportion of detection, with KRAS cfDNA mutations detected in 10.3%, 17,5% and 33.3% of cases with local, regional and systemic stages, respectively. We also detected KRAS cfDNA mutations in 3.7% (N=14) of healthy controls and in 4.3% (N=6) of subjects with chronic pancreatitis, but at significantly lower allelic fractions than in cases. Combining cfDNA KRAS mutations and CA19-9 plasma levels on a limited set of case-control samples did not improve the overall performance of the biomarkers as compared to CA19-9 alone. Whether the limited sensitivity and specificity observed in our series of KRAS mutations in plasma cfDNA as biomarkers for pancreatic cancer detection are attributable to methodological limitations or to the biology of cfDNA should be further assessed in large case-control series.
Published: 2016

27. Joint effects of intensity and duration of cigarette smoking on the risk of head and neck cancer: A bivariate spline model approach

Author: Philip Lazarus, Claire M. Healy, Richard B. Hayes, Rolando Herrero, Elaine M. Smith, Stefania Boccia, Leonardo F. Boaventura Rios, Paolo Boffetta, Dana Mates, Jerry Polesel, Marta Vilensky, Jose P. Zevallos, Diego Serraino, Gypsyamber D'Souza, Joshua E. Muscat, Kirsten B. Moysich, Yuan Chin Amy Lee, Mark P. Purdue, Carlo La Vecchia, Heribert Ramroth, Thomas L. Vaughan, Peter Thomson, Karl T. Kelsey, Nicola Torelli, Wolfgang Ahrens, Hermann Brenner, Lorenzo Richiardi, Victor Wünsch-Filho, Kristina Kjærheim, Beata Swiatkowska, Keitaro Matsuo, Fabio Levi, Erich M. Sturgis, Eva Negri, Lorenzo Simonato, Danièle Luce, Guo Pei Yu, Chu Chen, Pagona Lagiou, Silvia Franceschi, Andrew F. Olshan, Alexander W. Daudt, Antonio Agudo, Maria Paula Curado, Peter Rudnai, Tatiana V. Macfarlane, Zuo-Feng Zhang, Mia Hashibe, Paul Brennan, Tatiana Natasha Toporcov, Stimson P. Schantz, Maura L. Gillison, Isabelle Stücker, Tongzhang Zheng, Shu Chun Chuang, Oxana Shangina, Eleonora Fabianova, Hal Morgenstern, David I. Conway, Valeria Edefonti, Cristina Bosetti, Ariana Znaor, Leticia Fernandez, Michael D. McClean, Luigino Dal Maso, Neil D. Gross, Stephen M. Schwartz, Ivana Holcatova, Guojun Li, Ana M. B. Menezes, Francesco Pauli, Gioia Di Credico, Deborah M. Winn, Rosalina Jorge Koifman, Gwenn Menvielle, Gabriella Cadoni, Werner Garavello, Jolanda Lissowska, Università degli Studi di Milano [Milano] (UNIMI), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Glasgow, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), TW001500, National Institutes of Health, P30ES010126, National Institute of Environmental Health Sciences, Italian Ministry of Education, Università degli Studi di Milano, Jonsson Comprehensive Cancer Center, International Union Against Cancer, Fondo para la Investigacion Cientifica y Tecnologica Argentina, Institut Hospital del Mar d’Investigacions Mediquès (IMIM), Fundação de Amparo à Pesquisa no Estado de São Paulo, Spanish Government, European Community, Ministry of Science, Research and Arts Baden-Wurttemberg, German Ministry of Education and Research, Scientific Research grant from the Ministry of Education, Science, Sports, Culture and Technology of Japan, Labor and Welfare of Japan, Italian Foundation for Cancer Research, Di Credico G., Edefonti V., Polesel J., Pauli F., Torelli N., Serraino D., Negri E., Luce D., Stucker I., Matsuo K., Brennan P., Vilensky M., Fernandez L., Curado M.P., Menezes A., Daudt A.W., Koifman R., Wunsch-Filho V., Holcatova I., Ahrens W., Lagiou P., Simonato L., Richiardi L., Healy C., Kjaerheim K., Conway D.I., Macfarlane T.V., Thomson P., Agudo A., Znaor A., Boaventura Rios L.F., Toporcov T.N., Franceschi S., Herrero R., Muscat J., Olshan A.F., Zevallos J.P., La Vecchia C., Winn D.M., Sturgis E.M., Li G., Fabianova E., Lissowska J., Mates D., Rudnai P., Shangina O., Swiatkowska B., Moysich K., Zhang Z.-F., Morgenstern H., Levi F., Smith E., Lazarus P., Bosetti C., Garavello W., Kelsey K., McClean M., Ramroth H., Chen C., Schwartz S.M., Vaughan T.L., Zheng T., Menvielle G., Boccia S., Cadoni G., Hayes R.B., Purdue M., Gillison M., Schantz S., Yu G.-P., Brenner H., D'Souza G., Gross N.D., Chuang S.-C., Boffetta P., Hashibe M., Lee Y.-C.A., Dal Maso L., Di Credico, G, Edefonti, V, Polesel, J, Pauli, F, Torelli, N, Serraino, D, Negri, E, Luce, D, Stucker, I, Matsuo, K, Brennan, P, Vilensky, M, Fernandez, L, Curado, M, Menezes, A, Daudt, A, Koifman, R, Wunsch-Filho, V, Holcatova, I, Ahrens, W, Lagiou, P, Simonato, L, Richiardi, L, Healy, C, Kjaerheim, K, Conway, D, Macfarlane, T, Thomson, P, Agudo, A, Znaor, A, Boaventura Rios, L, Toporcov, T, Franceschi, S, Herrero, R, Muscat, J, Olshan, A, Zevallos, J, La Vecchia, C, Winn, D, Sturgis, E, Li, G, Fabianova, E, Lissowska, J, Mates, D, Rudnai, P, Shangina, O, Swiatkowska, B, Moysich, K, Zhang, Z, Morgenstern, H, Levi, F, Smith, E, Lazarus, P, Bosetti, C, Garavello, W, Kelsey, K, Mcclean, M, Ramroth, H, Chen, C, Schwartz, S, Vaughan, T, Zheng, T, Menvielle, G, Boccia, S, Cadoni, G, Hayes, R, Purdue, M, Gillison, M, Schantz, S, Yu, G, Brenner, H, D'Souza, G, Gross, N, Chuang, S, Boffetta, P, Hashibe, M, Lee, Y, Dal Maso, L, Di Credico, Gioia, Edefonti, Valeria, Polesel, Jerry, Pauli, Francesco, Torelli, Nicola, Serraino, Diego, Negri, Eva, Luce, Daniele, Stucker, Isabelle, Matsuo, Keitaro, Brennan, Paul, Vilensky, Marta, Fernandez, Leticia, Curado, Maria Paula, Menezes, Ana, Daudt, Alexander W., Koifman, Rosalina, Wunsch-Filho, Victor, Holcatova, Ivana, Ahrens, Wolfgang, Lagiou, Pagona, Simonato, Lorenzo, Richiardi, Lorenzo, Healy, Claire, Kjaerheim, Kristina, Conway, David I., Macfarlane, Tatiana V., Thomson, Peter, Agudo, Antonio, Znaor, Ariana, Boaventura Rios, Leonardo F., Toporcov, Tatiana N., Franceschi, Silvia, Herrero, Rolando, Muscat, Joshua, Olshan, Andrew F., Zevallos, Jose P., La Vecchia, Carlo, Winn, Deborah M., Sturgis, Erich M., Li, Guojun, Fabianova, Eleonora, Lissowska, Jolanda, Mates, Dana, Rudnai, Peter, Shangina, Oxana, Swiatkowska, Beata, Moysich, Kirsten, Zhang, Zuo-Feng, Morgenstern, Hal, Levi, Fabio, Smith, Elaine, Lazarus, Philip, Bosetti, Cristina, Garavello, Werner, Kelsey, Karl, Mcclean, Michael, Ramroth, Heribert, Chen, Chu, Schwartz, Stephen M., Vaughan, Thomas L., Zheng, Tongzhang, Menvielle, Gwenn, Boccia, Stefania, Cadoni, Gabriella, Hayes, Richard B., Purdue, Mark, Gillison, Maura, Schantz, Stimson, Yu, Guo-Pei, Brenner, Hermann, D'Souza, Gypsyamber, Gross, Neil D., Chuang, Shu-Chun, Boffetta, Paolo, Hashibe, Mia, Lee, Yuan-Chin Amy, Dal Maso, Luigino, Università degli Studi di Milano = University of Milan (UNIMI), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Male, Oral cavity and pharyngeal cancers, Cancer Research, Bivariate spline model, medicine.medical_treatment, Logistic regression, Substance Misuse, 0302 clinical medicine, Risk Factors, Laryngeal cancer, 80 and over, 2.2 Factors relating to the physical environment, Aetiology, 030223 otorhinolaryngology, Head and neck cancer, Cancer, Aged, 80 and over, Confounding, Middle Aged, 3. Good health, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Bivariate spline models, Cigarette smoking duration, Cigarette smoking intensity, Public Health and Health Services, Female, Oral Surgery, Adult, INHANCE, Oncology and Carcinogenesis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bivariate analysis, Cigarette Smoking, 03 medical and health sciences, Rare Diseases, Clinical Research, Tobacco, medicine, Humans, Oncology & Carcinogenesis, Dental/Oral and Craniofacial Disease, Aged, Settore MED/06 - ONCOLOGIA MEDICA, Tobacco Smoke and Health, business.industry, Prevention, Case-control study, Odds ratio, medicine.disease, Former Smoker, Good Health and Well Being, Case-Control Studies, Dentistry, Smoking cessation, business, Demography
Abstract: Objectives: \ud This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures.\ud \ud Materials and Methods: \ud We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework.\ud \ud Results: \ud For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30 years. In former smokers who quit ≥10 years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers.\ud \ud Conclusion: \ud Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.
Published: 2019

28. Sex specific associations in genome wide association analysis of renal cell carcinoma

Author: Lenka Foretova, Peng Li, Jean-François Deleuze, Rosamonde E. Banks, Ghislaine Scelo, Christopher G. Wood, Florence Le Calvez-Kelm, Mattias Johansson, Beata Świątkowska, Elio Riboli, Kevin M. Brown, Roger L. Milne, David Petillo, Fiona Bruinsma, Eunyoung Cho, Wong Ho Chow, Anne Boland, David C. Muller, Konstantin G. Skryabin, Börje Ljungberg, Hallie Carol, Demetrius Albanes, Loren Lipworth, Lisa Johnson, Gianluca Severi, Stephen J. Chanock, Slavisa Savic, Jolanta Lissowska, David Zaridze, Olivier Cussenot, Graham G. Giles, Garnet L. Anderson, Richard J. Kahnoski, Paul Brennan, Sabrina L. Noyes, Ulrike Peters, Behnoush Abedi-Ardekani, Howard D. Sesso, Bin Tean Teh, Peter Rudnai, Yuanqing Ye, Peter Kraft, Tony Fletcher, Geoffroy Durand, Douglas F. Easton, Ivana Holcatova, Eleonora Fabianova, Laura E. Beane Freeman, Xifeng Wu, Antonia Trichopoulou, James McKay, Peter Selby, Amanda Black, Marie Navratilova, Kathryn M. Wilson, Kim Overvad, J. Michael Gaziano, Toni K. Choueiri, Matthew L. Freedman, Mark P. Purdue, Matthieu Foll, Geraldine Cancel-Tassin, Sanja Radojevic-Skodric, Egor Prokhortchouk, Vladimir Janout, Gabriella Andreotti, Nivonirina Robinot, Nathaniel Rothman, Laurie Burdett, Todd L. Edwards, John Anema, Stefan Rascu, Leandro M. Colli, Dana Mates, Mark A. Preston, Viorel Jinga, Brian R. Lane, Lee E. Moore, Emily White, Delphine Bacq-Daian, Jan Lubinski, Raviprakash T. Sitaram, Simone Benhamou, Kvetoslava Koppova, Peter E. Clark, Mark Pomerantz, Mark Lathrop, Joshua N. Sampson, Wen Yi Huang, Mitchell J. Machiela, Jonathan N. Hofmann, Cezary Cybulski, Ruhina Shirin Laskar, Satu Männistö, Meredith Yeager, Zhaoming Wang, Valerie Gaborieau, Paul D.P. Pharoah, Stephanie J. Weinstein, Juhua Luo, Anush Mukeria, Stella Koutros, Salvatore Panico, Susanna C. Larsson, Alicja Wolk, Neal D. Freedman, Hélène Blanché, Vladimir Bencko, Cancer Research UK, Muller, David C [0000-0002-2350-0417], Li, Peng [0000-0002-0682-9819], Ye, Yuanqing [0000-0001-5708-8961], Holcatova, Ivana [0000-0002-1366-0337], Cancel-Tassin, Geraldine [0000-0002-9583-6382], Ljungberg, Borje [0000-0002-4121-3753], Milne, Roger L [0000-0001-5764-7268], Larsson, Susanna C [0000-0003-0118-0341], Banks, Rosamonde E [0000-0002-0042-8715], Selby, Peter J [0000-0002-3782-069X], Easton, Douglas F [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], Huang, Wen-Yi [0000-0002-4440-3368], Chanock, Stephen J [0000-0002-2324-3393], and Apollo - University of Cambridge Repository
Subjects: Oncology, Male, medicine.medical_specialty, Biochemistry & Molecular Biology, Quantitative Trait Loci, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, Sex Factors, Renal cell carcinoma, Internal medicine, Genetic variation, Genetics, medicine, Genetic predisposition, Odds Ratio, Humans, Genetic Predisposition to Disease, SUSCEPTIBILITY LOCUS, Carcinoma, Renal Cell, Genetics (clinical), Genetic association, Genetics & Heredity, 0604 Genetics, Science & Technology, Incidence (epidemiology), Computational Biology, Odds ratio, medicine.disease, CANCER, Kidney Neoplasms, Female, Life Sciences & Biomedicine, Sex ratio, Genome-Wide Association Study
Abstract: Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (OR(male)) = 0.83 [95% CI = 0.78-0.89], P(male) = 1.71 × 10(−8) compared with female odds ratio (OR(female)) = 0.98 [95% CI = 0.90–1.07], P(female) = 0.68) and 12q23.3 (intergenic, OR(male) = 0.75 [95% CI = 0.68-0.83], P(male) = 1.59 × 10(−8) compared with OR(female) = 0.93 [95% CI = 0.82–1.06], P(female) = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.
Published: 2019

29. Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma

Author: Kathryn M. Wilson, Sharon A. Savage, I-Min Lee, Stella Koutros, Gabriella Andreotti, Rosamonde E. Banks, Simone Benhamou, David Petillo, Laurie Burdette, Douglas F. Easton, Susanna C. Larsson, Peter Kraft, Marc Henrion, Lenka Foretova, Peng Li, H. Bas Bueno-de-Mesquita, Amanda Black, Konstantin G. Skryabin, Börje Ljungberg, Toni K. Choueiri, Loren Lipworth, Stephen J. Chanock, Robert Carreras-Torres, Sabrina L. Noyes, Olivier Cussenot, Marie Navratilova, Matthew L. Freedman, Mark Pomerantz, Wong-Ho Chow, David Zaridze, Eunyoung Cho, Lee E. Moore, James McKay, Lars J. Vatten, Ghislaine Scelo, Christopher G. Wood, Anush Mukeriya, Mirjana Mijuskovic, Jonathan N. Hofmann, Kevin M. Brown, Ulrike Peters, Valerie Gaborieau, Mark P. Purdue, Fiona Bruinsma, Richard J. Kahnoski, Paul Brennan, Susan J. Jordan, V. Janout, Cezary Cybulski, Timothy Eisen, Paul D.P. Pharoah, Howard S. Sesso, Hallie Carol, Neonila Szeszenia-Dabrowska, Garnet L. Anderson, Gianluca Severi, Céline Besse, Egor Prokhortchouk, Eric J. Duell, Satu Männistö, Geraldine Cancel-Tassin, Mitchell J. Machiela, Meredith Yeager, Eleonora Fabianova, Laura E. Beane Freeman, Mark A. Preston, Kvetoslava Koppova, John Anema, Jean-François Deleuze, G. Mark Lathrop, Victoria L. Stevens, Emily White, Zhaoming Wang, Stephanie J. Weinstein, Juhua Luo, Julie E. Buring, Viorel Jinga, Joshua N. Sampson, Peter Rudnai, Raviprakash T. Sitaram, Brian R. Lane, Stefan Rascu, Lisa Johnson, Jan Lubinski, Demetrius Albanes, Kristian Hveem, Leandro M. Colli, Dana Mates, Peter Selby, Miodrag Ognjanovic, Todd E. Edwards, Nathaniel Rothman, Richard S. Houlston, Matthieu Foll, Xifeng Wu, Peter E. Clark, Jolanta Lissowska, Vladimir Bencko, Ivana Holcatova, Anne Boland, James Larkin, Bin Tean Teh, J. Michael Gaziano, Hélène Blanché, Alicja Wolk, Neal D. Freedman, Federico Canzian, Mattias Johansson, Susan M. Gapstur, Yuanqing Ye, Tony Fletcher, Wen-Yi Huang, Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], Eisen, Tim [0000-0001-9663-4873], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Risk, Genetic variants, Urology, Genome-wide association study, macromolecular substances, urologic and male genital diseases, Polymorphism, Single Nucleotide, Risk Assessment, Article, 03 medical and health sciences, 0302 clinical medicine, Telomere Homeostasis, Renal cell carcinoma, Risk Factors, Mendelian randomization, Carcinoma, Leukocytes, Odds Ratio, Medicine, Humans, Genetic Predisposition to Disease, Carcinoma, Renal Cell, Genetics, Telomere length, business.industry, Case-control study, Odds ratio, Mendelian Randomization Analysis, Telomere, medicine.disease, female genital diseases and pregnancy complications, Kidney Neoplasms, 030104 developmental biology, Phenotype, 030220 oncology & carcinogenesis, Case-Control Studies, Cancer research, business, Genome-Wide Association Study
Abstract: BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p
Published: 2018
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30. Corrigendum re 'Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma' [Eur Urol 2017;72:747-54]

Author: Jolanta Lissowska, Douglas F. Easton, Ivana Holcatova, Matthieu Foll, Mark Pomerantz, Susan M. Gapstur, Peter E. Clark, Mitchell J. Machiela, Amanda Black, G. Mark Lathrop, Miodrag Ognjanovic, Marie Navratilova, Bin Tean Teh, Yuanqing Ye, Tony Fletcher, Matthew L. Freedman, Zhaoming Wang, Alicja Wolk, Wen-Yi Huang, Timothy Eisen, Dana Mates, Mark A. Preston, Eric J. Duell, I-Min Lee, Anush Mukeriya, Fiona Bruinsma, James McKay, Jan Lubinski, Kathryn M. Wilson, Sharon A. Savage, Neal D. Freedman, Julie E. Buring, Raviprakash T. Sitaram, Hallie Carol, Rosamonde E. Banks, Victoria L. Stevens, Garnet L. Anderson, Joshua N. Sampson, Simone Benhamou, Céline Besse, Stefan Rascu, Mark P. Purdue, Konstantin G. Skryabin, Börje Ljungberg, Kristian Hveem, Federico Canzian, Marc Henrion, Richard S. Houlston, Xifeng Wu, Wong-Ho Chow, Neonila Szeszenia-Dabrowska, Jonathan N. Hofmann, Anne Boland, Peter Rudnai, Eunyoung Cho, Egor Prokhortchouk, Stella Koutros, Lee E. Moore, Cezary Cybulski, Mirjana Mijuskovic, Valerie Gaborieau, Paul D.P. Pharoah, Susan J. Jordan, Vladimir Janout, Susanna C. Larsson, Viorel Jinga, Stephen J. Chanock, Loren Lipworth, Kevin M. Brown, Olivier Cussenot, Sabrina L. Noyes, Brian R. Lane, Laurie Burdette, Ulrike Peters, Satu Männistö, Meredith Yeager, Mattias Johansson, James Larkin, Stephanie J. Weinstein, Juhua Luo, Demetrius Albanes, Robert Carreras-Torres, J. Michael Gaziano, H. B. Bueno-De-Mesquita, Christopher G. Wood, Lisa Johnson, David Petillo, Howard S. Sesso, Hélène Blanché, Vladimir Bencko, Peng Li, Ghislaine Scelo, Geraldine Cancel-Tassin, Lars J. Vatten, Jean-François Deleuze, Peter Selby, John Anema, Emily White, Lenka Foretova, Kvetoslava Koppova, David Zaridze, Gianluca Severi, Gabriella Andreotti, Paul Brennan, Leandro M. Colli, Todd E. Edwards, Eleonora Fabianova, Laura E. Beane Freeman, Richard J. Kahnoski, Nathaniel Rothman, Peter Kraft, and Toni K. Choueiri
Subjects: Oncology, medicine.medical_specialty, business.industry, Urology, Genetic variants, MEDLINE, medicine.disease, Article, Telomere, 03 medical and health sciences, 0302 clinical medicine, Increased risk, Renal cell carcinoma, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030212 general & internal medicine, business
Abstract: It has come to our attention that authors Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Anush Mukeriya, Stefan Rascu, David Zaridze, Vladimir Bencko, and Cezary Cybulski were not assigned to the correct affiliations. Their correct affiliations are as in the list above. Conflicts of interest: The authors have nothing to disclose.
Published: 2018

31. No association between global DNA methylation in peripheral blood and lung cancer risk in nonsmoking women: Results from a multicenter study in Eastern and Central Europe

Author: Eleonora Fabianova, Dana Mates, Lenka Foretova, Vladimir Bencko, Ioan Nicolae Mates, Vladimir Janout, Ghislaine Scelo, Paolo Boffetta, Jolanta Lissowska, Peter Rudnai, Meng-Hua Tao, David Zaridze, Ann Davis, Jia Chen, Davis, A., Tao, M.-H., Chen, J., Scelo, G., Bencko, V., Fabianova, E., Foretova, L., Janout, V., Lissowska, J., Mates, D., Mates, I.N., Rudnai, P., Zaridze, D., and Boffetta, P.
Subjects: 0301 basic medicine, Oncology, Adult, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Epidemiology, Luma, Logistic regression, Risk Assessment, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Biomarkers, Tumor, Medicine, Humans, Young adult, Lung cancer, Aged, global dna methylation, business.industry, Genome, Human, Public Health, Environmental and Occupational Health, Case-control study, Methylation, Non-Smokers, DNA Methylation, Middle Aged, medicine.disease, 3. Good health, Europe, 030104 developmental biology, 030220 oncology & carcinogenesis, Case-Control Studies, DNA methylation, Immunology, Blood Buffy Coat, Female, business
Abstract: Alterations in global DNA methylation have been suggested to play an important role in cancer development. We evaluated the association of global DNA methylation in peripheral blood with the risk of lung cancer in nonsmoking women from six countries in Central and Eastern Europe. This multicenter case-control study included primary, incident lung cancer cases diagnosed from 1998 to 2001 and controls frequency-matched for geographic area, sex, and age. Global methylation was assessed in peripheral blood DNA from 83 nonsmoking female cases and 181 nonsmoking female controls using the luminometric methylation assay (LUMA). Unconditional logistic regression models were used to estimate associations between DNA methylation in the blood and the risk of lung cancer. LUMA methylation level was not associated with the risk of lung cancer in nonsmoking women. Associations were not significantly different according to different strata of age, BMI, alcohol drinking, or second-hand tobacco smoke exposure status. In our study of nonsmoking women, the LUMA methylation level in peripheral blood was not associated with the risk of lung cancer. Our findings do not support an association of global blood DNA methylation with the risk of lung cancer in nonsmoking women. © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Published: 2018

32. The INHANCE consortium: toward a better understanding of the causes and mechanisms of head and neck cancer

Author: Neonila Szeszenia-Dabrowska, Dana Mates, Danièle Luce, Lorenzo Simonato, José Eluf-Neto, Michael Pawlita, Elaine M. Smith, Kim De Ruyck, Gwenn Menvielle, Cristina Bosetti, Deborah M. Winn, David Zaridze, Gabriella Cadoni, Keitaro Matsuo, Diego Serraino, Isabelle Stücker, Richard B. Hayes, Mia Hashibe, Andrew F. Olshan, Robert I. Haddad, David I. Conway, Guo-Pei Yu, Tatiana V. Macfarlane, Simone Benhamou, Chu Chen, Brenda Diergaarde, Maura L. Gillison, Paul Brennan, Michael D. McClean, Kristina Kjærheim, Vladimir Bencko, Peter Rudnai, Guojun Li, Eleonora Fabianova, Pagona Lagiou, Thomas L. Vaughan, Witold Zatonski, Silvia Franceschi, Gypsyamber D'Souza, Rayjean J. Hung, Victor Wünsch-Filho, Antonio Agudo, Yuan Chin Amy Lee, Martin Lacko, Erich M. Sturgis, Xavier Castellsagué, Fabio Levi, Luigino Dal Maso, Jolanta Lissowska, Carlo La Vecchia, Franco Merletti, Steve Schwartz, Oxana Shangina, Ariana Znaor, Gregory T. Wolf, Jonathan N. Hofmann, Ivana Holcatova, Wolfgang Ahrens, Rolando Herrero, Alexander W. Daudt, Kirsten B. Moysich, Heribert Ramroth, Karl T. Kelsey, Maria Paula Curado, Zuo-Feng Zhang, Ana M. B. Menezes, Philip Lazarus, Laura S. Rozek, Tongzhang Zheng, Paolo Boffetta, Jose P. Zevallos, Peter Thomson, Claire M. Healy, Stefania Boccia, Wilbert H.M. Peters, Stimson P. Schantz, Marta Vilensky, Joshua E. Muscat, Hermann Brenner, Sergio Koifman, Geoffrey Liu, Manoj B. Mahimkar, Leticia Fernandez, Winn, D.M., Lee, Y.-C., Hashibe, M., Boffetta, P., Agudo, A., Ahrens, W., Bencko, V., Benhamou, S., Boccia, S., Bosetti, C., Brennan, P., Brenner, H., Cadoni, G., Castellsague, X., Chen, C., Conway, D., Curado, M.P., D'Souza, G., Maso, L.D., Daudt, A.W., Ruyck, K.D., Diergaarde, B., Eluf-Neto, J., Fabianova, E., Fernandez, L., Franceschi, S., Gillison, M., Haddad, R.I., Hayes, R., Healy, C., Herrero, R., Hofmann, J., Holcátová, I., Hung, R., Kelsey, K., Kjaerheim, K., Koifman, S., Vecchia, C.L., Lacko, M., Lagiou, P., Lazarus, P., Levi, F., Li, G., Lissowska, J., Liu, G., Luce, D., Macfarlane, T., Mahimkar, M., Mates, D., Matsuo, K., McClean, M., Menezes, A., Menvielle, G., Merletti, F., Moysich, K., Muscat, J., Olshan, A., Pawlita, M., Peters, W.H.M., Ramroth, H., Rozek, L., Rudnai, P., Schantz, S., Schwartz, S., Serraino, D., Shangina, O., Simonato, L., Smith, E., Stucker, I., Sturgis, E.M., Szeszenia-Dabrowska, Neonila and Thomson, P., Vaughan, T., Vilensky, M., Wolf, G., Wünsch-Filho, V., Yu, G., Zaridze, D., Zatonski, W., Zevallos, J.P., Zhang, Z.-F., Zheng, T.-Z., and Znaor, A.
Subjects: Larynx, Data Pooling, Oncology, medicine.medical_specialty, Research groups, Alcohol Drinking, Scientific productivity, Risk Factors, Internal medicine, Epidemiology, Humans, Medicine, Cooperative Behavior, Family history, Settore MED/42 - IGIENE GENERALE E APPLICATA, General Dentistry, business.industry, Smoking, Head and neck cancer, Confounding, medicine.disease, Diet, Surgery, medicine.anatomical_structure, Socioeconomic Factors, Otorhinolaryngology, Head and Neck Neoplasms, epidemiology, head and neck cancer, Settore MED/31 - OTORINOLARINGOIATRIA, business
Abstract: The International Head and Neck Cancer Epidemiology (INHANCE) consortium is a collaboration of research groups leading large epidemiology studies to improve the understanding of the causes and mechanisms of head and neck cancer. The consortium includes investigators of 35 studies who have pooled their data on 25 500 patients with head and neck cancer (i.e., cancers of the oral cavity, oropharynx, hypopharynx, and larynx) and 37 100 controls. The INHANCE analyses have confirmed that tobacco use and alcohol intake are key risk factors of these diseases and have provided precise estimates of risk and dose response, the benefit of quitting, and the hazard of smoking even a few cigarettes per day. Other risk factors include short height, lean body mass, low education and income, and a family history of head and neck cancer. Risk factors are generally similar for oral cavity, pharynx, and larynx, although the magnitude of risk may vary. Some major strengths of pooling data across studies include more precise estimates of risk and the ability to control for potentially confounding factors and to examine factors that may interact with each other. The INHANCE consortium provides evidence of the scientific productivity and discoveries that can be obtained from data pooling projects. © 2015 John Wiley & Sons A/S.
Published: 2015

33. Effect of Occupational Exposures on Lung Cancer Susceptibility: A Study of Gene–Environment Interaction Analysis

Author: Paul Brennan, Vladimir Bencko, Lenka Foretova, Beata Świątkowska, Dana Mates, Eleonora Fabianova, Jyoti Malhotra, Paolo Boffetta, Peter Rudnai, Valerie Gaborieau, Samantha Sartori, Isabelle Stücker, Neonila Szeszenia-Dabrowska, Jolanta Lissowska, Vladimir Janout, David Zaridze, Malhotra, J., Sartori, S., Brennan, P., Zaridze, D., Szeszenia-Dabrowska, N., wiatkowska, B., Rudnai, P., Lissowska, J., Fabianova, E., Mates, D., Bencko, V., Gaborieau, V., Stücker, I., Foretova, L., Janout, V., and Boffetta, P.
Subjects: Male, Oncology, medicine.medical_specialty, Pathology, Lung Neoplasms, Genotype, Epidemiology, Single-nucleotide polymorphism, Genome-wide association study, Polymorphism, Single Nucleotide, Risk Factors, Occupational Exposure, Internal medicine, Humans, SNP, Medicine, Gene–environment interaction, Occupational exposures - lung cancer, Lung cancer, business.industry, Case-control study, Cancer, Middle Aged, medicine.disease, Lung cancer susceptibility, Europe, Occupational Diseases, Case-Control Studies, Female, Gene-Environment Interaction, business, Genome-Wide Association Study, Signal Transduction
Abstract: Background: Occupational exposures are known risk factors for lung cancer. Role of genetically determined host factors in occupational exposure–related lung cancer is unclear. Methods: We used genome-wide association (GWA) data from a case–control study conducted in 6 European countries from 1998 to 2002 to identify gene–occupation interactions and related pathways for lung cancer risk. GWA analysis was performed for each exposure using logistic regression and interaction term for genotypes, and exposure was included in this model. Both SNP-based and gene-based interaction P values were calculated. Pathway analysis was performed using three complementary methods, and analyses were adjusted for multiple comparisons. We analyzed 312,605 SNPs and occupational exposure to 70 agents from 1,802 lung cancer cases and 1,725 cancer-free controls. Results: Mean age of study participants was 60.1 ± 9.1 years and 75% were male. Largest number of significant associations (P ≤ 1 × 10−5) at SNP level was demonstrated for nickel, brick dust, concrete dust, and cement dust, and for brick dust and cement dust at the gene-level (P ≤ 1 × 10−4). Approximately 14 occupational exposures showed significant gene–occupation interactions with pathways related to response to environmental information processing via signal transduction (P < 0.001 and FDR < 0.05). Other pathways that showed significant enrichment were related to immune processes and xenobiotic metabolism. Conclusion: Our findings suggest that pathways related to signal transduction, immune process, and xenobiotic metabolism may be involved in occupational exposure–related lung carcinogenesis. Impact: Our study exemplifies an integrative approach using pathway-based analysis to demonstrate the role of genetic variants in occupational exposure–related lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 24(3); 570–9. ©2015 AACR.
Published: 2015

34. Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

Author: Maria Paula Curado, Zuo-Feng Zhang, Hal Morgenstern, Philip Lazarus, Jolanta Lissowska, Paul Brennan, Leticia Fernandez, Peter Rudnai, Chu Chen, Julien Berthiller, Paolo Boffetta, Eleonora Fabianova, Andrew F. Olshan, Sergio Koifman, Mia Hashibe, Rolando Herrero, Luigino Dal Maso, Erich M. Sturgis, Fabio Levi, José Eluf-Neto, Deborah M. Winn, Xavier Castellsagué, Alexander W. Daudt, Neolilia Szeszenia-Dabrowska, Stephen M. Schwartz, Karl T. Kelsey, Silva Franceschi, Joshua E. Muscat, Simone Benhamou, Ana M. B. Menezes, Elena Matos, Richard B. Hayes, Carlo La Vecchia, Mia M. Gaudet, Shu Chun Chuang, David Zaridze, V. Wünsch-Filho, Renato Talamini, Alexandru Bucur, Qingyi Wei, Gaudet, M.M., Olshan, A.F., Chuang, S.-C., Berthiller, J., Zhang, Z.-F., Lissowska, J., Zaridze, D., Winn, D.M., Wei, Q., Talamini, R., Szeszenia-Dabrowska, N., Sturgis, E.M., Schwartz, S.M., Rudnai, P., Eluf-Neto, J., Muscat, J., Morgenstern, H., Menezes, A., Matos, E., Bucur, A., Levi, F., Lazarus, P., La Vecchia, C., Koifman, S., Kelsey, K., Herrero, R., Hayes, R.B., Franceschi, S., Wunsch-Filho, V., Fernandez, L., Fabianova, E., Daudt, A.W., Dal Maso, L., Curado, M.P., Chen, C., Castellsague, X., Benhamou, S., Boffetta, P., Brennan, P., and Hashibe, M.
Subjects: Male, Epidemiology, Overweight, 0302 clinical medicine, Risk Factors, Odds Ratio, pooled analysi, 030212 general & internal medicine, Child, 10. No inequality, Prospective cohort study, Body mass index, Cancer, Aged, 80 and over, 2. Zero hunger, Incidence, Smoking, Confounding, General Medicine, Middle Aged, 3. Good health, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Female, medicine.symptom, case-control, Adult, medicine.medical_specialty, INHANCE, Adolescent, Alcohol Drinking, Young Adult, 03 medical and health sciences, Thinness, medicine, Humans, Risk factor, Aged, business.industry, Case-control study, Odds ratio, United States, Surgery, Case-Control Studies, International Head and Neck Cancer Epidemiology, head and neck cancer, business, Consortium, Demography
Abstract: Background: Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. Methods: We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. Results: Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) =18.5 kg/m2 (2.13, 1.75-2.58) and reduced for BMI >25.0-30.0 kg/m2 (0.52, 0.44-0.60) and BMI =30 kg/m2 (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m2. These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI =18.5 kg/m2 was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m2 was present only in smokers and drinkers. Conclusions: In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies. © The Author 2010; Published by Oxford University Press on behalf of the International Epidemiological Association. All rights reserved.
Published: 2017

35. Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls

Author: Neonilia Szeszenia-Dabrowska, Olaide Y. Raji, John R. Gosney, Margaret R. Spitz, Darren R. Brenner, James McKay, Inger Njølstad, Kari Stefansson, Rayjean J. Hung, Chu Chen, H.-Erich Wichmann, Juncheng Dai, Christopher I. Amos, Dakai Zhu, John K. Field, Yufei Wang, Thomas Muley, Hans E. Krokan, Gary E. Goodman, Vladimir Bencko, Mari Nelis, Vladimir Janout, Mala Pande, Valerie Gaborieau, Tõnu Vooder, Frank Skorpen, Hongbing Shen, Michael J. Thun, Kristjan Välk, Peter Rudnai, Albert Rosenberger, Heike Bickeböller, T. Eisen, Jolanta Lissowska, John R. McLaughlin, Steven A. Narod, Thorunn Rafnar, David C. Christiani, Maiken Elvestad Gabrielsen, Demetrius Albanes, Maria Teresa Landi, Lenka Foretova, Ying Chen, Triantafillos Liloglou, Hendrik Dienemann, Paul Brennan, Richard S. Houlston, Angela Risch, Yang Zhao, Wei Chen, Andres Metspalu, David Zaridze, Maria Timofeeva, Xifeng Wu, Younghun Han, Gudmar Thorleifsson, Simone Benhamou, Eleonora Fabianova, Neil E. Caporaso, Lars J. Vatten, Mark Lathrop, and Dana Mates
Subjects: Asian Continental Ancestry Group, Risk, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714, Lung Neoplasms, European Continental Ancestry Group, Genome-wide association study, Single-nucleotide polymorphism, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714, Biology, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, 0302 clinical medicine, Asian People, CDKN2A, Genetic variation, Genetics, medicine, Genetic predisposition, Humans, Lung cancer, Molecular Biology, CHEK2, Genetics (clinical), 030304 developmental biology, Genetic association, 0303 health sciences, Association Studies Articles, Genetic Variation, General Medicine, medicine.disease, 3. Good health, genetic variation, lung cancer risk, 030220 oncology & carcinogenesis, Case-Control Studies, Genome-Wide Association Study
Abstract: Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p21-6p22 and 15q25.1 associated with lung cancer risk. Several other genetic regions including variants of CHEK2 (22q12), TP53BP1 (15q15) and RAD52 (12p13) have been demonstrated to influence lung cancer risk in candidate- or pathway-based analyses. To identify novel risk variants for lung cancer, we performed a meta-analysis of 16 GWASs, totaling 14 900 cases and 29 485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P = 7.2 × 10(-16)), 6p21 (P = 2.3 × 10(-14)) and 15q25 (P = 2.2 × 10(-63)). Furthermore, we demonstrated histology-specific effects for 5p15, 6p21 and 12p13 loci but not for the 15q25 region. Subgroup analysis also identified a novel disease locus for squamous cell carcinoma at 9p21 (CDKN2A/p16(INK4A)/p14(ARF)/CDKN2B/p15(INK4B)/ANRIL; rs1333040, P = 3.0 × 10(-7)) which was replicated in a series of 5415 Han Chinese (P = 0.03; combined analysis, P = 2.3 × 10(-8)). This large analysis provides additional evidence for the role of inherited genetic susceptibility to lung cancer and insight into biological differences in the development of the different histological types of lung cancer. peerReviewed
Published: 2017

36. Alcohol and lung cancer risk among never smokers: A pooled analysis from the international lung cancer consortium and the SYNERGY study

Author: Gordon, Fehringer, Darren R, Brenner, Zuo-Feng, Zhang, Yuan-Chin Amy, Lee, Keitaro, Matsuo, Hidemi, Ito, Qing, Lan, Paolo, Vineis, Mattias, Johansson, Kim, Overvad, Elio, Riboli, Antonia, Trichopoulou, Carlotta, Sacerdote, Isabelle, Stucker, Paolo, Boffetta, Paul, Brennan, David C, Christiani, Yun-Chul, Hong, Maria Teresa, Landi, Hal, Morgenstern, Ann G, Schwartz, Angela S, Wenzlaff, Gad, Rennert, John R, McLaughlin, Curtis C, Harris, Susan, Olivo-Marston, Irene, Orlow, Bernard J, Park, Marjorie, Zauderer, Juan M, Barros Dios, Alberto, Ruano Raviña, Jack, Siemiatycki, Anita, Koushik, Philip, Lazarus, Ana, Fernández-Somoano, Adonina, Tardon, Loic, Le Marchand, Hermann, Brenner, Kai-Uwe, Saum, Eric J, Duell, Angeline S, Andrew, Neonila, Szeszenia-Dabrowska, Jolanta, Lissowska, David, Zaridze, Peter, Rudnai, Eleonora, Fabianova, Dana, Mates, Lenka, Foretova, Vladimir, Janout, Vladimir, Bencko, Ivana, Holcatova, Angela Cecilia, Pesatori, Dario, Consonni, Ann, Olsson, Kurt, Straif, and Rayjean J, Hung
Subjects: Male, Asia, Lung Neoplasms, Alcohol Drinking, education, Oncology and Carcinogenesis, Cardiovascular, Article, DIET, Cohort Studies, Alcohol Use and Health, Substance Misuse, liquor, ENVIRONMENTAL TOBACCO-SMOKE, Risk Factors, Tobacco, Humans, EXPOSURE, Oncology & Carcinogenesis, wine, Lung, METAANALYSIS, Cancer, Aged, Science & Technology, Tobacco Smoke and Health, alcohol, Prevention, Alcoholic Beverages, Smoking, food and beverages, CONSUMPTION, Middle Aged, ETIOLOGY, Stroke, Europe, Alcoholism, lung cancer, Good Health and Well Being, Oncology, Case-Control Studies, North America, Respiratory, beer, LIFE-STYLE, Female, Life Sciences & Biomedicine, BEVERAGE PREFERENCE, 1112 Oncology And Carcinogenesis
Abstract: It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.
Published: 2016

37. Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

Author: Stefania Boccia, Wilbert H.M. Peters, Kristina Kjærheim, James McKay, Christopher I. Amos, David I. Conway, Dana Mates, Ana Maria Menezes, Antonio Agudo, Brenda Diergaarde, Rolando Herrero, Valerie Gaborieau, Martin Lacko, Cristina Canova, Neonila Szeszenia-Dąbrowska, Lorenzo Richiardi, Xiangjun Xiao, Victor Wünsch-Filho, Pagona Lagiou, David Zaridze, Maria Paula Curado, H. Bas Bueno-de-Mesquita, Mark C. Weissler, Rayjean J. Hung, Paolo Boffetta, Claire M. Healy, Marcos Brasilino de Carvalho, Fábio Daumas Nunes, Steve Thomas, Devasena Anantharaman, Paul Brennan, Mattias Johansson, Geoffrey Liu, Oxana Shangina, Ariana Znaor, Corina Lesseur, Eleonora Fabianova, Gabriella Cadoni, Andy R Ness, Eloiza H. Tajara, Gary J. Macfarlane, Jennifer R. Grandis, Annika Steffen, Jerry Polesel, Max Robinson, Marta Vilensky, Andrew F. Olshan, Wolfgang Ahrens, Silvia Franceschi, Amelie Chabrier, José Eluf-Neto, Jolanta Lissowska, Ivana Holcatova, Xavier Castellsagué, Nofer Institute of Occupational Medicine, Łódź, Poland, RS: GROW - R2 - Basic and Translational Cancer Biology, MUMC+: MA Keel Neus Oorheelkunde (9), Lesseur, C., Diergaarde, B., Olshan, A.F., Wünsch-Filho, V., Ness, A.R., Liu, G., Lacko, M., Eluf-Neto, J., Franceschi, S., Lagiou, P., Macfarlane, G.J., Richiardi, L., Boccia, S., Polesel, J., Kjaerheim, K., Zaridze, D., Johansson, M., Menezes, A.M., Curado, M.P., Robinson, M., Ahrens, W., Canova, C., Znaor, A., Castellsagué, X., Conway, D.I., Holcátová, I., Mates, D., Vilensky, M., Healy, C.M., Szeszenia-Dabrowska, N., Fabiánová, E., Lissowska, J., Grandis, J.R., Weissler, M.C., Tajara, E.H., Nunes, F.D., De Carvalho, M.B., Thomas, S., Hung, R.J., Peters, W.H.M., Herrero, R., Cadoni, G., Bueno-De-Mesquita, H.B., Steffen, A., Agudo, A., Shangina, O., Xiao, X., Gaborieau, V., Chabrier, A., Anantharaman, D., Boffetta, P., Amos, C.I., McKay, J.D., and Brennan, P.
Subjects: Male, 0301 basic medicine, Epidemiology, Genome-wide association study, Gastroenterology, Genome-wide association studies, INCIDÊNCIA, HLA Antigens, Genetics research, Aged, Case-Control Studies, Female, Genetic Markers, Genetic Variation, Haplotypes, Humans, Middle Aged, Mouth, Mouth Neoplasms, Papillomaviridae, Papillomavirus Infections, Pharyngeal Neoplasms, Genetic Predisposition to Disease, Genome-Wide Association Study, Genetics, Oral cancer, genetic research, 3. Good health, Settore MED/31 - OTORINOLARINGOIATRIA, medicine.medical_specialty, Papillomaviruses, Genome-wide - oral cavity and pharyngeal cancer, Human leukocyte antigen, Biology, Article, 03 medical and health sciences, Internal medicine, medicine, Allele, Papil·lomavirus, Haplotype, Case-control study, Odds ratio, oral cancer, medicine.disease, Càncer de boca, 030104 developmental biology, Nasopharyngeal carcinoma, Immunology, Imputation (genetics)
Abstract: We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers. Genotyping performed at the Center for Inherited Disease Research (CIDR) was funded through the U.S. National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780-0. Genotyping for shared controls with the Lung OncoArray initiative was funded through the grant X01HG007492-0. Corina Lesseur undertook this work during the tenure of a Postdoctoral Fellowship awarded by the International Agency for Research on Cancer. The funders did not participate in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge all of the participants involved in this research and the funders and support. We thank Dr. Leticia Fernandez (Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba) for her contribution to the IARC ORC multicenter study. We are also grateful to Sergio Koifman (Escola Nacional de Saúde Pública, Rio de Janeiro, Brazil) for his contribution to the IARC Latin America multicenter study (Sergio Koifman passed away in May 2014) and to Xavier Castellsagué from the ARCAGE Barcelona Center who recently passed away (June 2016). The University of Pittsburgh head and neck cancer case-control study is supported by National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01-CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). The authors thank all the members of the GENCAPO team. The HN5000 study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034), the views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19 CA148127) and the Cancer Care Ontario Research Chair. The alcohol-related cancers and genetic susceptibility study in Europe (ARCAGE) was funded by the European Commission’s 5th Framework Program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte, and Padova University (CPDA057222).The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG 2011 10491 and IG2013 14220 to SB, and Fondazione Veronesi to SB. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). The IARC Central Europe study was supported by European Commission’s INCO-COPERNICUS Program (IC15-CT98-0332), NIH/National Cancer Institute grant CA92039, and the World Cancer Research Foundation grant WCRF 99A28.The IARC Oral Cancer Multicenter study was funded by: grant S06 96 202489 05F02 from Europe against Cancer; Grants FIS 97/0024, FIS 97/0662, and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; UICC Yamagiwa-Yoshida Memorial International Cancer Study; National Cancer Institute of Canada; Italian Association for Research on Cancer; and the Pan American Health Organization. The coordination of EPIC study is financially supported
Published: 2016

38. The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study

Author: Elisabete Weiderpass, J. Brent Richards, Peter Selby, Emily White, Peng Li, Ghislaine Scelo, David C. Muller, Garnet L. Anderson, Nicholas J. Timpson, David Zaridze, Mattias Johansson, Poulami Barman, Laura E. Beane Freeman, Alexander S. Parker, Simone Benhamou, Mark P. Purdue, Ingrid Winship, Victoria L. Stevens, Wong-Ho Chow, Valerie Gaborieau, Neal D. Freedman, Jean-François Deleuze, Juhua Luo, Philip C Haycock, Kevin M. Brown, Todd L. Edwards, Jeanette E. Eckel-Passow, Tony Fletcher, Ulrike Peters, Anush Mukeriya, Christel Häggström, Fiona Bruinsma, Timothy Eisen, Richard J. Kahnoski, George Davey Smith, I-Min Lee, Laurie Burdette, Lisa Johnson, Hallie Carol, Alicja Wolk, Jolanta Lissowska, Zhaoming Wang, Stephen J. Chanock, Yuanqing Ye, Sabrina L. Noyes, Jan Lubinski, Marie Navratilova, Matthew L. Freedman, Xifeng Wu, Ivana Holcatova, Stella Koutros, Vladimir Janout, Richard S. Houlston, James D. McKay, Toni K. Choueiri, Anne Boland, Susanna C. Larsson, Rosamonde E. Banks, Gabriella Andreotti, Sanja Radojevic-Skodric, Egor Prokhortchouk, Eunyoung Cho, Stefan Rascu, Paul Brennan, Hélène Blanché, David Petillo, James Larkin, Konstantin G. Skryabin, Börje Ljungberg, Marc J. Gunter, Viorel Jinga, Howard D. Sesso, Matthieu Foll, Brian R. Lane, Peter Rudnai, Jean-Guillaume Garnier, J. Michael Gaziano, Geraldine Cancel-Tassin, Caroline L Relton, Julie E. Buring, Meredith Yeager, Raviprakash T. Sitaram, Kristian Hveem, Loren Lipworth, Olivier Cussenot, Bin Tean Teh, Robert Carreras-Torres, Peter E. Clark, Vladimir Bencko, Simona Ognjanovic, Mark Pomerantz, Stephanie J. Weinstein, Mitchell J. Machiela, G. Mark Lathrop, Dana Mates, Lenka Foretova, Gianluca Severi, Bradley C. Leibovich, Leandro M. Colli, Daniela Mariosa, Marc Henrion, Satu Männistö, Susan J. Jordan, Kathryn M. Wilson, Richard M. Martin, Eleonora Fabianova, Jonathan N. Hofmann, Lars J. Vatten, Susan M. Gapstur, Cezary Cybulski, Wen-Yi Huang, Douglas F. Easton, Lee E. Moore, Cancer Research UK, Carreras-Torres, Robert [0000-0002-2925-734X], Timpson, Nicolas J [0000-0002-7141-9189], Haycock, Philip C [0000-0001-5001-3350], Brown, Kevin M [0000-0002-8558-6711], Machiela, Mitchell J [0000-0001-6538-9705], Li, Peng [0000-0002-0682-9819], Radojevic-Skodric, Sanja [0000-0002-5395-8285], Holcatova, Ivana [0000-0002-1366-0337], Mates, Dana [0000-0002-6219-9807], Mukeriya, Anush [0000-0002-6847-9295], Fabianova, Eleonora [0000-0002-5519-8427], Jinga, Viorel [0000-0001-7632-5328], Cancel-Tassin, Geraldine [0000-0002-9583-6382], Cussenot, Olivier [0000-0002-9912-0533], Weiderpass, Elisabete [0000-0003-2237-0128], Bruinsma, Fiona [0000-0002-9356-2015], Jordan, Susan J [0000-0002-4566-1414], Severi, Gianluca [0000-0001-7157-419X], Winship, Ingrid [0000-0001-8535-6003], Fletcher, Tony [0000-0003-3385-200X], Larsson, Susanna C [0000-0003-0118-0341], Wolk, Alicja [0000-0001-7387-6845], Banks, Rosamonde E [0000-0002-0042-8715], Beane Freeman, Laura E [0000-0003-1294-4124], Weinstein, Stephanie [0000-0002-3834-1535], Edwards, Todd L [0000-0003-4318-6119], Gapstur, Susan M [0000-0002-1934-2110], Stevens, Victoria L [0000-0003-0259-4407], Carol, Hallie [0000-0001-8890-9785], Pomerantz, Mark M [0000-0003-4914-1157], Freedman, Neal D [0000-0003-0074-1098], Huang, Wen-Yi [0000-0002-4440-3368], Petillo, David [0000-0001-7234-4644], Anderson, Garnet L [0000-0001-5087-7837], Moore, Lee E [0000-0002-5957-8283], Henrion, Marc [0000-0003-1242-839X], Barman, Poulami [0000-0002-4604-9868], Choueiri, Toni K [0000-0002-9201-3217], McKay, James D [0000-0002-1787-3874], Richards, J Brent [0000-0002-3746-9086], Martin, Richard M [0000-0002-7992-7719], Davey Smith, George [0000-0002-1407-8314], Brennan, Paul [0000-0002-0518-8714], and Apollo - University of Cambridge Repository
Subjects: Blood Glucose, Male, Physiology, Epidemiology, Blood Pressure, Genome-wide association study, 030204 cardiovascular system & hematology, urologic and male genital diseases, Bioinformatics, Biochemistry, Vascular Medicine, Body Mass Index, Endocrinology, Mathematical and Statistical Techniques, 0302 clinical medicine, Risk Factors, Renal cell carcinoma, Medicine and Health Sciences, Insulin, Medicine, 030212 general & internal medicine, 2. Zero hunger, Cancer Risk Factors, Statistics, Public Health, Global Health, Social Medicine and Epidemiology, Mendelian Randomization Analysis, Genomics, 11 Medical And Health Sciences, General Medicine, Lipids, Kidney Neoplasms, 3. Good health, Oncology, Physiological Parameters, Physical Sciences, Female, ICEP, Research Article, Genetic Markers, medicine.medical_specialty, Research and Analysis Methods, Instrumental Variable Analysis, Carcinomas, 03 medical and health sciences, General & Internal Medicine, Mendelian randomization, Genome-Wide Association Studies, Genetics, Carcinoma, Humans, VDP::Medisinske Fag: 700, Obesity, Statistical Methods, Carcinoma, Renal Cell, Diabetic Endocrinology, Cancer och onkologi, business.industry, Body Weight, Renal Cell Carcinoma, Cancers and Neoplasms, Biology and Life Sciences, Computational Biology, Cancer, Human Genetics, Genome Analysis, medicine.disease, Hormones, VDP::Medical disciplines: 700, Genitourinary Tract Tumors, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Diabetes Mellitus, Type 2, Medical Risk Factors, Cancer and Oncology, Etiology, business, Mathematics, Genome-Wide Association Study
Abstract: Background Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation. Methods and findings Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose. Conclusions This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk., Using mendelian randomization approaches, Paul Brennan and colleagues reveal an association between 12 obesity-related factors, including insulin and the development of renal cell carcinoma., Author summary Why was this study done? Traditional observational studies wherein putative risk factors are measured directly have found several obesity-related factors associated with increased risk of renal cell carcinoma (RCC). Traditional observational studies are subject to confounding and reverse causation and have not been able to disentangle which obesity-related risk factors directly influence RCC risk. This study used an alternative methodology commonly referred to as mendelian randomization (MR). MR circumvents many of the inherent limitations of traditional observational study by use of genetic proxies of putative risk factors when evaluating their associations with disease risk, as they are not subject to reverse causation and are less likely to be confounded by other risk factors. What did the researchers do and find? First, we used large-scale genome-wide association studies (GWAS) to identify genetic variants associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose. Second, these genetic variants were used as proxies for the above-mentioned risk factors and evaluated in relation RCC risk using GWAS data from 10,000 RCC patients and 20,000 control participants. Based on these genetic data, we found that multiple measures of obesity, as well as diastolic blood pressure (DBP) and fasting insulin, are associated with RCC risk. In contrast, we found little evidence for an association with RCC risk for systolic blood pressure (SBP), circulating lipids, overall diabetes, or fasting glucose. What do these findings mean? This study provided robust and confirmatory evidence of an important role of obesity as an important risk factor of RCC. Further confirmatory evidence was found for elevated DBP as a risk factor of RCC, but it is not clear why DBP rather than SBP is important in RCC. The study, to our knowledge, provided novel evidence of an important role of circulating insulin in RCC etiology. This study provided some novel insights into the pathways involved in mediating the risk increase in RCC that is caused by obesity, most notably through insulin and DBP, but further research is needed to fully elucidate the important relationship between obesity and RCC.
Published: 2019

39. P025 Lung cancer risk among firefighters when accounting for tobacco smoking – preliminary results from a pooled analysis of case-control studies from europe, canada, new zealand and china

Author: Neil Pearce, Neonila Szeszenia-Dabrowska, Ignatius Tak-sun Yu, Susan Peters, Neil E. Caporaso, Ann Olsson, Isabelle Stücker, Hermann Pohlabeln, Lenka Foretova, Adonina Tardón, Carolina Bigert, Paul A. Demers, Dirk Taeger, Vladimir Janout, John K. Field, Joachim Schüz, Maria Teresa Landi, David Zaridze, Lorenzo Simonato, John McLaughlin, Kurt Straif, Wolfgang Ahrens, Peter Rudnai, Florence Guida, Benjamin Kendzia, Jack Siemiatycki, Karl-Heinz Jöckel, Rodica Stanescu Dumitru, Jérôme Lavoué, Lap Ah Tse, Lorenzo Richardi, Hans Kromhout, Dario Mirabelli, Jolanta Lissowska, Paolo Boffetta, Heinz-Erich Wichmann, Irene Brüske, Beate Pesch, Eleonora Fabianova, Angela Cecilia Pesatori, Andrea 't Mannetje, Thomas Brüning, Vladimir Bencko, Per Gustavsson, and Roel Vermeulen
Subjects: Smoke, Lung, business.industry, Case-control study, Odds ratio, medicine.disease, Logistic regression, Confidence interval, medicine.anatomical_structure, Pooled analysis, Environmental health, Medicine, business, Lung cancer
Abstract: Objectives Firefighters are potentially exposed to a wide variety of chemical compounds during the course of their work and inhalation is considered to be the major source of exposure. A large number of human carcinogens have been detected in smoke at fires. The aim was to investigate the risk of lung cancer among firefighters, while controlling for smoking habits. Methods We used data from the SYNERGY project including pooled information on lifetime work histories and smoking habits for 14,748 male lung cancer cases and 17,543 controls from 14 case-control studies conducted in Europe, Canada, New Zealand and China. There were 190 men who had ever worked as a firefighter (based on ISCO-68), among them 86 cases and 104 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression, adjusted for study, age, smoking, and ever employment in an occupation with established lung cancer risk. Results We observed no increased risk of lung cancer in firefighters, neither before (OR = 1.03, 95% CI: 0.77–1.38) nor after (OR = 0.95, 95% CI: 0.68–1.32) adjustment for smoking and exposure to other occupational lung carcinogens. There was no evidence of a trend of increasing lung cancer risk with increasing duration of work as a firefighter (p = 0.58) and no significant heterogeneity in lung cancer risk among firefighters across the studies. None of the major histological subtypes of lung cancer was associated with work as a firefighter. Conclusions We found no evidence of an excess lung cancer risk related to occupational exposure as a firefighter, when lifetime history of tobacco smoking and exposure to other occupational lung carcinogens was taken into account.
Published: 2016

40. Relation of allium vegetables intake with head and neck cancers: evidence from the INHANCE consortium

Author: Valentina Guercio, Dana Mates, Paul Brennan, Diego Serraino, Eleonora Fabianova, Fabio Levi, Carlo La Vecchia, Yuan Chin Amy Lee, Federica Turati, Mark P. Purdue, Hermann Brenner, Peter Rudnai, Oxana Shangina, Paolo Boffetta, Zuo-Feng Zhang, Cristina Bosetti, Alessandra Tavani, Carlotta Galeone, Jola Lissowska, Karl T. Kelsey, Michael D. McClean, Neonila Szeszenia-Dabrowska, Mia Hashibe, Claudio Pelucchi, Richard B. Hayes, Thomas L. Vaughan, Galeone, C., Turati, F., Zhang, Z.-F., Guercio, V., Tavani, A., Serraino, D., Brennan, P., Fabianova, E., Lissowska, J., Mates, D., Rudnai, P., Shangina, O., Szeszenia-Dabrowska, N., Vaughan, T.L., Kelsey, K., Mcclean, M., Levi, F., Hayes, R.B., Purdue, M.P., Bosetti, C., Brenner, H., Pelucchi, C., Lee, Y.-C.A., Hashibe, M., Boffetta, P., and La Vecchia, C.
Subjects: Oncology, medicine.medical_specialty, Article, Allium, Rare Diseases, Food Sciences, Risk Factors, Internal medicine, Epidemiology, Vegetables, medicine, Humans, Dental/Oral and Craniofacial Disease, Head and neck, Garlic, Cancer, Nutrition and Dietetics, biology, Nutrition & Dietetics, business.industry, Head and neck cancer, food and beverages, medicine.disease, biology.organism_classification, Surgery, Diet, Allium vegetables - head and neck cancers, Logistic Models, Head and Neck Neoplasms, Case-Control Studies, Allium vegetables, Public Health and Health Services, Onion, business, Biotechnology, Food Science
Abstract: Scope: Only a few studies analyzed the role of allium vegetables with reference to head and neck cancers (HNC), with mixed results. We investigated the potential favorable role of garlic and onion within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Methods and results: We analyzed pooled individual-level data from eight case-control studies, including 4590 cases and 7082 controls. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between garlic and onion intakes and HNC risk. Compared with no or low garlic use, the ORs of HNC were 0.95 (95% CI 0.71-1.27) for intermediate and 0.74 (95% CI 0.55-0.99) for high garlic use (p for trend = 0.02). The ORs of HNC for increasing categories of onion intake were 0.91 (95% CI 0.68-1.21) for >1 to =3 portions per week, and 0.83 (95% CI 0.60-1.13) for >3 portions per week (p for trend = 0.02), as compared to
Published: 2015

41. Identification of lung cancer histology-specific variants applying Bayesian framework variant prioritization approaches within the TRICL and ILCCO consortia

Author: Keitaro Matsuo, Neil E. Caporaso, John R. Gosney, Juncheng Dai, Maiken Elvestad Gabrielsen, Margaret R. Spitz, Frank Skorpen, Tõnu Vooder, Neonila Szeszenia-Dabrowska, Paul Brennan, Brian E. Henderson, Shelley S. Tworoger, Vladimir Bencko, Xuchen Zong, Younghun Han, Olaide Y. Raji, Yufei Wang, Andres Metspalu, Hidemi Ito, Irene Orlow, Michael W. Marcus, Eleonora Fabianova, Chu Chen, James McKay, Ping Yang, Gary E. Goodman, Hans E. Krokan, Demetrius Albanes, Timothy Eisen, Geoffrey Liu, Ying Chen, Triantafillos Liloglou, Jolanta Lissowska, Lynne R. Wilkens, Mari Nelis, Mark Lathrop, John K. Field, Fumihiko Matsuda, Di Zhang, Yongyue Wei, Dana Mates, Peter Rudnai, Yonathan Brhane, Jun She, Victoria L. Stevens, Inger Njølstad, Hongbing Shen, Darren R. Brenner, Maria Teresa Landi, Susan M. Gapstur, Li Su, Michael P.A. Davies, David Zaridze, Loic Le Marchand, John R. McLaughlin, Dong Xie, Paolo Boffetta, Rayjean J. Hung, Peter Broderick, Albert Rosenberger, Hendrik Dienemann, Lenka Foretova, Thomas Muley, Christopher I. Amos, Vladimi Janout, David C. Christiani, Joachim Heinrich, Yafang Li, Lars J. Vatten, Mattias Johansson, Richard S. Houlston, Xifeng Wu, Kristjan Välk, Wei V. Chen, Heike Bickeböller, Angela Risch, Maria Timofeeva, Brenner, D.R., Amos, C.I., Brhane, Y., Timofeeva, M.N., Caporaso, N., Wang, Y., Christiani, D.C., Bickeböller, H., Yang, P., Albanes, D., Stevens, V.L., Gapstur, S., McKay, J., Boffetta, P., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Mates, D., Bencko, V., Foretova, L., Janout, V., Krokan, H.E., Skorpen, F., Gabrielsen, M.E., Vatten, L., Njølstad, I., Chen, C., Goodman, G., Lathrop, M., Vooder, T., Välk, K., Nelis, M., Metspalu, A., Broderick, P., Eisen, T., Wu, X., Zhang, D., Chen, W., Spitz, M.R., Wei, Y., Su, L., Xie, D., She, J., Matsuo, K., Matsuda, F., Ito, H., Risch, A., Heinrich, J., Rosenberger, A., Muley, T., Dienemann, H., Field, J.K., Raji, O., Chen, Y., Gosney, J., Liloglou, T., Davies, M.P.A., Marcus, M., McLaughlin, J., Orlow, I., Han, Y., Li, Y., Zong, X., Johansson, M., Liu, G., Tworoger, S.S., Le Marchand, L., Henderson, B.E., Wilkens, L.R., Dai, J., Shen, H., Houlston, R.S., Landi, M.T., Brennan, P., and Hung, R.J.
Subjects: Cancer Research, Lung Neoplasms, Bayesian probability, Genome-wide association study, Original Manuscript, Computational biology, Adenocarcinoma, Bioinformatics, 03 medical and health sciences, Bayes' theorem, 0302 clinical medicine, medicine, Humans, Genetic Predisposition to Disease, Lung cancer, 030304 developmental biology, Genetic association, 0303 health sciences, business.industry, Case-control study, Bayes Theorem, General Medicine, medicine.disease, 3. Good health, ComputingMethodologies_PATTERNRECOGNITION, 030220 oncology & carcinogenesis, Meta-analysis, Case-Control Studies, Carcinoma, Squamous Cell, business, Genome-Wide Association Study
Abstract: Large-scale genome-wide association studies (GWAS) have likely uncovered all common variants at the GWAS significance level. Additional variants within the suggestive range (0.0001> P > 5×10(-8)) are, however, still of interest for identifying causal associations. This analysis aimed to apply novel variant prioritization approaches to identify additional lung cancer variants that may not reach the GWAS level. Effects were combined across studies with a total of 33456 controls and 6756 adenocarcinoma (AC; 13 studies), 5061 squamous cell carcinoma (SCC; 12 studies) and 2216 small cell lung cancer cases (9 studies). Based on prior information such as variant physical properties and functional significance, we applied stratified false discovery rates, hierarchical modeling and Bayesian false discovery probabilities for variant prioritization. We conducted a fine mapping analysis as validation of our methods by examining top-ranking novel variants in six independent populations with a total of 3128 cases and 2966 controls. Three novel loci in the suggestive range were identified based on our Bayesian framework analyses: KCNIP4 at 4p15.2 (rs6448050, P = 4.6×10(-7)) and MTMR2 at 11q21 (rs10501831, P = 3.1×10(-6)) with SCC, as well as GAREM at 18q12.1 (rs11662168, P = 3.4×10(-7)) with AC. Use of our prioritization methods validated two of the top three loci associated with SCC (P = 1.05×10(-4) for KCNIP4, represented by rs9799795) and AC (P = 2.16×10(-4) for GAREM, represented by rs3786309) in the independent fine mapping populations. This study highlights the utility of using prior functional data for sequence variants in prioritization analyses to search for robust signals in the suggestive range.
Published: 2015

42. A systematic investigation of the contribution of genetic variation within the MHC region to HPV seropositivity

Author: Paolo Boffetta, Huibo Wang, Mark Lathrop, Tim Waterboer, James McKay, Paul Brennan, Peter Rudnai, Eleonora Fabianova, Vladimir Janout, Valerie Gaborieau, Yao Zhao, Dan Chen, Amelie Chabrier, Jolanta Lissowska, Michael Pawlita, Vladimir Bencko, Lenka Foretova, Ioan Nicolae Mates, David Zaridze, Neonila Szeszenia-Dabrowska, Ulf Gyllensten, Chen, D., Gaborieau, V., Zhao, Y., Chabrier, A., Wang, H., Waterboer, T., Zaridze, D., Lissowska, J., Rudnai, P., Fabianova, E., Bencko, V., Janout, V., Foretova, L., Mates, I.N., Szeszenia-Dabrowska, N., Boffetta, P., Pawlita, M., Lathrop, M., Gyllensten, U., Brennan, P., and McKay, J.D.
Subjects: Male, medicine.medical_specialty, viruses, Single-nucleotide polymorphism, Human leukocyte antigen, Biology, Major histocompatibility complex, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Major Histocompatibility Complex, HLA Antigens, Genetic variation, Genetics, medicine, Odds Ratio, High-risk mucosal types of human papillomavirus (HPV) - anogenital and oropharyngeal cancers, Humans, Genetic Predisposition to Disease, Allele, Molecular Biology, Papillomaviridae, Genetics (clinical), Alleles, Papillomavirus Infections, virus diseases, Mucous membrane, Genetic Variation, General Medicine, medicine.disease, Virology, female genital diseases and pregnancy complications, medicine.anatomical_structure, Haplotypes, Case-Control Studies, Immunology, biology.protein, Medical genetics, Female, Skin cancer
Abstract: High-risk mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas cutaneous types (e.g. HPV8 and 77) are suspected to be involved in non-melanoma skin cancer. The antibody response to HPVs is a key determinant of protective immunity, but not all infected individuals seroconvert. Genetic variability of the host may have large impact on seroconversion. A previous genome-wide association study (GWAS) has identified a susceptibility locus (rs41270488) for HPV8 seropositivity within the major histocompatibility complex (MHC) region. To further study this locus, we imputed alleles at classical leukocyte antigen (HLA) loci using HLA*IMP:02 with a reference panel from the HapMap Project and the 1958 Birth Cohort, and conducted an integrated analysis among 4811 central European subjects to assess the contribution of classical HLA alleles and gene copy number variation (CNV) at the hypervariable DRB locus within the MHC region to HPV seropositivity at both the individual HPV type level and the phylogenetic species level. Our study provides evidence that the association noted between rs41270488 and HPV8 seropositivity is driven by two independent variants, namely DQB1*0301 [odds ratio (OR) = 1.51, 95% confidence interval (CI) = 1.36-1.68, P = 1.0 × 10-14] and DRB1*1101 (OR = 1.89, 95%CI = 1.57-2.28, P = 1.5 × 10-11) within the HLA class II region. Additionally, we identified two correlated alleles DRB1*0701 (OR = 1.67, 95%CI = 1.41-1.98, P = 2.6 × 10-9) and DQA1*0201 (OR = 1.67, 95%CI = 1.38-1.93, P = 1.7 × 10-8), to be associated with HPV77 seropositivity. Comparable results were observed through imputation using SNP2HLA with another reference panel from the Type 1 diabetes Genetics Consortium. This study provides support for an important role of HLA class II alleles in antibody response to HPV infection. © The Author 2015.
Published: 2015

43. Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium

Author: Gabriella Cadoni, Stefania Boccia, Alexander W. Daudt, Maria Paula Curado, Philip Lazarus, Kristina Kjærheim, Renato Talamini, Zuo-Feng Zhang, Wolfgang Ahrens, Thomas L. Vaughan, Marta Vilensky, Joshua E. Muscat, Mark P. Purdue, Qingyi Wei, OtÃ¡vio Alberto Curioni, Guo Pei Yu, Claire M. Healy, Keitaro Matsuo, Dana Mates, Yuan Chin Amy Lee, Rolando Herrero, Paolo Boffetta, JosÃ© Leopoldo Ferreira Antunes, Mia Hashibe, Elaine M. Smith, Lorenzo Richiardi, Oxana Shangina, Chu Chen, Antonio Agudo, Victor WÃ¼nsch Filho, Sergio Koifman, Pagona Lagiou, Deborah M. Winn, Michael D. McClean, Cristina Canova, Heribert Ramroth, Karl T. Kelsey, Peter Rudnai, Peter Thomson, Leticia Fernandez, P Brennan, Neonila Szeszenia-Dabrowska, Eleonora Fabianova, Hal Morgenstern, Stephen M. Schwartz, Xavier Castellsagué, Jolanta Lissowska, Andrew F. Olshan, Tatiana V. Macfarlane, Carlo La Vecchia, Ivana Holcatova, Ariana Znaor, Raquel Ajub Moyses, JosÃ© Eluf-Neto, David I. Conway, Tatiana Natasha Toporcov, Stimson P. Schantz, Richard B. Hayes, Fabio Levi, Erich M. Sturgis, Luigino Dal Maso, Ana M. B. Menezes, Silvia Franceschi, International Prevention Research Institute (IPRI), The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Toporcov, T.N., Znaor, A., Zhang, Z.-F., Yu, G.-P., Winn, D.M., Wei, Q., Vilensky, M., Vaughan, T., Thomson, P., Talamini, R., Szeszenia-Dabrowska, N., Sturgis, E.M., Smith, E., Shangina, O., Schwartz, S.M., Schantz, S., Rudnai, P., Richiardi, L., Ramroth, H., Purdue, M.P., Olshan, A.F., Eluf-Neto, J., Muscat, J., Moyses, R.A., Morgenstern, H., Menezes, A., McClean, M., Matsuo, K., Mates, D., Macfarlane, T.V., Lissowska, J., Levi, F., Lazarus, P., Vecchia, C.L., Lagiou, P., Koifman, S., Kjaerheim, K., Kelsey, K., Holcatova, I., Herrero, R., Healy, C., Hayes, R.B., Franceschi, S., Fernandez, L., Fabianova, E., Daudt, A.W., Curioni, O.A., Maso, L.D., Curado, M.P., Conway, D.I., Chen, C., Castellsague, X., Canova, C., Cadoni, G., Brennan, P., Boccia, S., Antunes, J.L.F., Ahrens, W., Agudo, A., Boffetta, P., Hashibe, M., Lee, Y.-C.A., and Filho, V.W.
Subjects: Male, Aging, Epidemiology, head and neck cancer (HNC), Adult Age Factors Alcohol Drinking/*epidemiology Case-Control Studies Female Genetic Predisposition to Disease Head and Neck Neoplasms/*epidemiology/genetics Humans Incidence Male Middle Aged Odds Ratio Registries Risk Factors Sex Factors Smoking/*epidemiology Head and neck neoplasms alcohol drinking diet smoking, Risk Factors, Odds Ratio, Registries, Family history, Young adult, Cancer, Incidence (epidemiology), Incidence, Medicine (all), Statistics, Smoking, Age Factors, General Medicine, Middle Aged, 3. Good health, Public Health and Health Services, Female, Settore MED/31 - OTORINOLARINGOIATRIA, Adult, medicine.medical_specialty, Alcohol Drinking, Head and neck neoplasms, smoking, Rare Diseases, Sex Factors, Clinical Research, Internal medicine, Tobacco, medicine, Humans, Genetic Predisposition to Disease, Dental/Oral and Craniofacial Disease, Tobacco Smoke and Health, business.industry, Prevention, Head and neck cancer, Alcohol drinking, Diet, Case-Control Studies, Head and Neck Neoplasms, Case-control study, prognostic factors, Odds ratio, medicine.disease, Confidence interval, Surgery, Good Health and Well Being, Attributable risk, head and neck cancer, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, diet, Digestive Diseases, business
Abstract: Toporcov, Tatiana Natasha Znaor, Ariana Zhang, Zuo-Feng Yu, Guo-Pei Winn, Deborah M Wei, Qingyi Vilensky, Marta Vaughan, Thomas Thomson, Peter Talamini, Renato Szeszenia-Dabrowska, Neonila Sturgis, Erich M Smith, Elaine Shangina, Oxana Schwartz, Stephen M Schantz, Stimson Rudnai, Peter Richiardi, Lorenzo Ramroth, Heribert Purdue, Mark P Olshan, Andrew F Eluf-Neto, Jose Muscat, Joshua Moyses, Raquel Ajub Morgenstern, Hal Menezes, Ana McClean, Michael Matsuo, Keitaro Mates, Dana Macfarlane, Tatiana V Lissowska, Jolanta Levi, Fabio Lazarus, Philip La Vecchia, Carlo Lagiou, Pagona Koifman, Sergio Kjaerheim, Kristina Kelsey, Karl Holcatova, Ivana Herrero, Rolando Healy, Claire Hayes, Richard B Franceschi, Silvia Fernandez, Leticia Fabianova, Eleonora Daudt, Alexander W Curioni, Otavio Alberto Maso, Luigino Dal Curado, Maria Paula Conway, David I Chen, Chu Castellsague, Xavier Canova, Cristina Cadoni, Gabriella Brennan, Paul Boccia, Stefania Antunes, Jose Leopoldo Ferreira Ahrens, Wolfgang Agudo, Antonio Boffetta, Paolo Hashibe, Mia Lee, Yuan-Chin Amy Filho, Victor Wunsch eng FIRCA TW01500/TW/FIC NIH HHS/ K07CA104231/CA/NCI NIH HHS/ P01CA068384/CA/NCI NIH HHS/ P30ES010126/ES/NIEHS NIH HHS/ P50CA90388/CA/NCI NIH HHS/ R01CA048996/CA/NCI NIH HHS/ R01CA100264/CA/NCI NIH HHS/ R01CA30022/CA/NCI NIH HHS/ R01CA51845/CA/NCI NIH HHS/ R01CA61188/CA/NCI NIH HHS/ R01DA11386/DA/NIDA NIH HHS/ R01DE012609/DE/NIDCR NIH HHS/ R01DE11979/DE/NIDCR NIH HHS/ R01DE13110/DE/NIDCR NIH HHS/ R01DE13158/DE/NIDCR NIH HHS/ R01ES11740/ES/NIEHS NIH HHS/ R03CA113157/CA/NCI NIH HHS/ R03CA77954/CA/NCI NIH HHS/ R03DE016611/DE/NIDCR NIH HHS/ R21ES011667/ES/NIEHS NIH HHS/ T32CA09142/CA/NCI NIH HHS/ U01CA96134/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2015/01/24 06:00 Int J Epidemiol. 2015 Feb;44(1):169-85. doi: 10.1093/ije/dyu255. Epub 2015 Jan 22.; International audience; BACKGROUND: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. METHODS: We pooled data from 25 case-control studies and conducted separate analyses for adults 45 years old ('older adults', 17700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI=9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking=5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR=2.27 (95% CI=1.26, 4.10)], but not in the older adults [OR=1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults. CONCLUSIONS: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.
Published: 2015

44. A rare truncating BRCA2 variant and genetic susceptibility to upper aerodigestive tract cancer

Author: Maria Paula Curado, Ioan Nicolae Mates, Pagona Lagiou, Kristina Kjærheim, Graham Byrnes, Jerry Polesel, Ariana Znaor, Lenka Foretová, James McKay, Valerie Gaborieau, Keitaro Matsuo, Manoj B. Mahimkar, Maxime Vallée, Stefania Boccia, Devasena Anantharaman, Wolfgang Ahrens, Antonio Agudo, Ana Paula de O. Menezes, Paolo Boffetta, Cristina Canova, Tatiana V. Macfarlane, Vladimir Bencko, Lorenzo Richiardi, Jolanta Lissowska, Manon Delahaye-Sourdeix, Jan Lubinski, David Zaridze, Ivana Holcatova, Silvia Franceschi, V. Wünsch-Filho, Amelie Chabrier, Nalin S. Thakker, Marcin Lener, Ewa Jaworowska, Maria Timofeeva, Leticia Fernández Garrote, Tanuja A. Samant, Claire M. Healy, Thangarajan Rajkumar, Vladimir Janout, Sergio Koifman, David I. Conway, Neonilia Szeszenia-Dabrowska, Paul Brennan, Eleonora Fabianova, Xavier Castellsagué, José Eluf-Neto, Luigi Barzan, International Prevention Research Institute (IPRI), The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Delahaye-Sourdeix, M., Anantharaman, D., Timofeeva, M.N., Gaborieau, V., Chabrier, A., Vallée, M.P., Lagiou, P., Holcátová, I., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsagué, X., Macfarlane, T.V., Barzan, L., Canova, C., Thakker, N.S., Conway, D.I., Znaor, A., Healy, C.M., Ahrens, W., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Fabianova, E., Mates, I.N., Bencko, V., Foretova, L., Janout, V., Curado, M.P., Koifman, S., Menezes, A., Wünsch-Filho, V., Eluf-Neto, J., Boffetta, P., Fernández Garrote, L., Polesel, J., Lener, M., Jaworowska, E., Lubinski, J., Boccia, S., Rajkumar, T., Samant, T.A., Mahimkar, M.B., Matsuo, K., Franceschi, S., Byrnes, G., Brennan, P., and Mckay, J.D.
Subjects: Oncology, Adult, Aged, Alcohol Drinking, BRCA2 Protein, Carcinoma, Squamous Cell, Case-Control Studies, Female, Genetic Predisposition to Disease, Head and Neck Neoplasms, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Risk Assessment, Risk Factors, Smoking, Polymorphism, Single Nucleotide, Cancer Research, Medicine (all), HOMOLOGOUS RECOMBINATION, Adult Aged Alcohol Drinking/adverse effects/epidemiology BRCA2 Protein/*genetics Carcinoma, BRCA2 genetic variants - Breast cancer - Lung squamous cell carcinoma, POPULATION, Single Nucleotide, 3. Good health, PREVALENCE, Single Nucleotide Risk Assessment Risk Factors Smoking/adverse effects/epidemiology, SQUAMOUS-CELL CARCINOMA, Risk assessment, medicine.medical_specialty, Single-nucleotide polymorphism, Biology, Brief Communication, Breast cancer, Internal medicine, medicine, Carcinoma, Genetic predisposition, SNP, GENOME-WIDE ASSOCIATION, Polymorphism, Settore MED/42 - IGIENE GENERALE E APPLICATA, POLYMORPHIC STOP CODON, cancer, Japanese, breast cancer, neoplasms, genetics, smoking, BRAC2 gene, single nucleotide polymorphism, squamous cell carcinoma of lung, breast cancer risk, squamous cell carcinoma, upper aerodigestive tract, upper aerodigestive tract neoplasms, genetic predisposition to disease, BRCA2 protein, mutation, cancer risk, Case-control study, Odds ratio, Squamous Cell/*genetics Case-Control Studies Female Genetic Predisposition to Disease Head and Neck Neoplasms/*genetics Humans Logistic Models Male Middle Aged Odds Ratio *Polymorphism, medicine.disease, Squamous Cell, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Delahaye-Sourdeix, Manon Anantharaman, Devasena Timofeeva, Maria N Gaborieau, Valerie Chabrier, Amelie Vallee, Maxime P Lagiou, Pagona Holcatova, Ivana Richiardi, Lorenzo Kjaerheim, Kristina Agudo, Antonio Castellsague, Xavier Macfarlane, Tatiana V Barzan, Luigi Canova, Cristina Thakker, Nalin S Conway, David I Znaor, Ariana Healy, Claire M Ahrens, Wolfgang Zaridze, David Szeszenia-Dabrowska, Neonilia Lissowska, Jolanta Fabianova, Eleonora Mates, Ioan Nicolae Bencko, Vladimir Foretova, Lenka Janout, Vladimir Curado, Maria Paula Koifman, Sergio Menezes, Ana Wunsch-Filho, Victor Eluf-Neto, Jose Boffetta, Paolo Fernandez Garrote, Leticia Polesel, Jerry Lener, Marcin Jaworowska, Ewa Lubinski, Jan Boccia, Stefania Rajkumar, Thangarajan Samant, Tanuja A Mahimkar, Manoj B Matsuo, Keitaro Franceschi, Silvia Byrnes, Graham Brennan, Paul McKay, James D eng 1R03DE020116/DE/NIDCR NIH HHS/ R01CA092039 05/05S1/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural 2015/04/04 06:00 J Natl Cancer Inst. 2015 Apr 2;107(5). pii: djv037. doi: 10.1093/jnci/djv037. Print 2015 May.; International audience; Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10(-10)) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.
Published: 2015

45. Interpreting biomarker data from the COPHES/DEMOCOPHES twin projects : using external exposure data to understand biomarker differences among countries

Author: Louis Bloemen, Lisbeth E. Knudsen, Eleonora Fabianova, Marc E. Fischer, Ioana-Rodica Lupsa, Ulrike Fiddicke, Pierre Crettaz, Pierre Biot, Holger M. Koch, Margarete Seiwert, Ovnair Sepai, Jeanette K.S. Nielsen, Marike Kolossa-Gehring, Ludwine Casteleyn, Silvia Gómez, Michael P. Ryan, Andromachi Katsonouri, E. Den Hond, Milena Horvat, Marek Jakubowski, Gudrun Koppen, Gerda Schwedler, Peter Rudnai, Kristin Larsson, Andrea Krsková, Dominique Aerts, Anca Elena Gurzau, Karen Exley, Danuta Ligocka, Arno C. Gutleb, J. Tratnik Snoj, Reinhard Joas, Greet Schoeters, Anke Joas, Darja Mazej, S. González, Juergen Angerer, David S. Evans, Milena Černá, Eva Govarts, Marta Esteban, Sónia Namorado, Adamos Hadjipanayis, Argelia Castaño, Katarina Halzlova, Szilvia Kozepesy, Marika Berglund, Andrea Lehmann, Hanny Willems, Roel Smolders, M. F. Reis, and Repositório da Universidade de Lisboa
Subjects: Adult, Rural Population, Urban Population, human biomonitoring, Interpreting, External exposure data, Biochemistry, chemistry.chemical_compound, Surveys and Questionnaires, Environmental health, Biomonitoring, Environmental monitoring, Humans, Child, Cotinine, Biology, Environmental quality, General Environmental Science, external exposure data, Smoking, Hair analysis, Interpretation, COPHES/DEMOCOPHES, Environmental Exposure, Mercury, Environmental exposure, Fish consumption, Europe, Human biomonitoring, Chemistry, Seafood, chemistry, Data Interpretation, Statistical, Government Regulation, Environmental Pollutants, Female, Human medicine, Biomarkers, Exposure data, Cadmium, Environmental Monitoring, Hair
Abstract: © 2014 Elsevier Inc. All rights reserved., In 2011 and 2012,the COPHES/DEMOCOPHES twin projects performedt he first ever harmonized human biomonitoring survey in 17 European countries.In more than 1800 mother–child pairs,individual lifestyle data were collected and cadmium,cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples.While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures,the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality and lifestyle.In general,13 countries having implemented DEMOCOPHES provided high quality data from external sources that were relevant for interpretation purposes.However,some data were not available for reporting or were not in line with predefined specifications. Therefore,only part of the external information could be included in the statistical analyses. Nonetheless,there was a highly significant correlation between national levels of fish consumption and mercury in hair,the strength of antismoking legislation was significantly related to urinary cotinine levels,and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality.These results again show the potential of biomonitoring data to provide added value for(the evaluation of)evidence-informed policy making., The European Commission,Belgium,DG for Research and Innovation(RTD),who is funding COPHES in the 7th Framework Programme(No.244237).DEMOCOPHES(LIFE09ENV/BE/000410)received 50% funding through the LIFE+ financial instrument of the European Union(DGENV),as well as 50% through funding received from the DEMOCOPHES partners.
Published: 2015

46. Determinants of Anti-S Immune Response at 12 Months after SARS-CoV-2 Vaccination in a Multicentric European Cohort of Healthcare Workers—ORCHESTRA Project

Author: Ludovica Leomanni, Giulia Collatuzzo, Emanuele Sansone, Emma Sala, Giuseppe De Palma, Stefano Porru, Gianluca Spiteri, Maria Grazia Lourdes Monaco, Daniela Basso, Sofia Pavanello, Maria Luisa Scapellato, Francesca Larese Filon, Luca Cegolon, Marcella Mauro, Vittorio Lodi, Tiziana Lazzarotto, Ivan Noreña, Christina Reinkemeyer, Le Thi Thu Giang, Eleonóra Fabiánová, Jozef Strhársky, Marco Dell’Omo, Nicola Murgia, Lucía A. Carrasco-Ribelles, Concepción Violán, Dana Mates, Agripina Rascu, Luigi Vimercati, Luigi De Maria, Shuffield S. Asafo, Giorgia Ditano, Mahsa Abedini, and Paolo Boffetta
Subjects: COVID-19, coronavirus, vaccine, serology, antibody level, immunization, Medicine
Abstract: Background: The effectiveness of the immunity provided by SARS-CoV-2 vaccines is an important public health issue. We analyzed the determinants of 12-month serology in a multicenter European cohort of vaccinated healthcare workers (HCW). Methods: We analyzed the sociodemographic characteristics and levels of anti-SARS-CoV-2 spike antibodies (IgG) in a cohort of 16,101 vaccinated HCW from eleven centers in Germany, Italy, Romania, Slovakia and Spain. Considering the skewness of the distribution, the serological levels were transformed using log or cubic standardization and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log or cubic antibody level and the corresponding 95% confidence interval (CI) for different factors and combined them in random-effects meta-analyses. Results: We included 16,101 HCW in the analysis. A high antibody level was positively associated with age (RR = 1.04, 95% CI = 1.00–1.08 per 10-year increase), previous infection (RR = 1.78, 95% CI 1.29–2.45) and use of Spikevax [Moderna] with combinations compared to Comirnaty [BioNTech/Pfizer] (RR = 1.07, 95% CI 0.97–1.19) and was negatively associated with the time since last vaccine (RR = 0.94, 95% CI 0.91–0.98 per 30-day increase). Conclusions: These results provide insight about vaccine-induced immunity to SARS-CoV-2, an analysis of its determinants and quantification of the antibody decay trend with time since vaccination.
Published: 2023
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47. Multimorbidity and Serological Response to SARS-CoV-2 Nine Months after 1st Vaccine Dose: European Cohort of Healthcare Workers—Orchestra Project

Author: Concepción Violán, Lucía A. Carrasco-Ribelles, Giulia Collatuzzo, Giorgia Ditano, Mahsa Abedini, Christian Janke, Christina Reinkemeyer, Le Thi Thu Giang, Filippo Liviero, Maria Luisa Scapellato, Marcella Mauro, Francesca Rui, Stefano Porru, Gianluca Spiteri, Maria Grazia Lourdes Monaco, Angela Carta, Marina Otelea, Agripina Rascu, Eleonóra Fabiánová, Zuzana Klöslová, Paolo Boffetta, and Pere Torán-Monserrat
Subjects: SARS-CoV-2, antibodies, IgG, humoral immunity, seroprevalence, COVID-19, Medicine
Abstract: Understanding antibody persistence concerning multimorbidity is crucial for vaccination policies. Our goal is to assess the link between multimorbidity and serological response to SARS-CoV-2 nine months post-first vaccine. We analyzed Healthcare Workers (HCWs) from three cohorts from Italy, and one each from Germany, Romania, Slovakia, and Spain. Seven groups of chronic diseases were analyzed. We included 2941 HCWs (78.5% female, 73.4% ≥ 40 years old). Multimorbidity was present in 6.9% of HCWs. The prevalence of each chronic condition ranged between 1.9% (cancer) to 10.3% (allergies). Two regression models were fitted, one considering the chronic conditions groups and the other considering whether HCWs had diseases from ≥2 groups. Multimorbidity was present in 6.9% of HCWs, and higher 9-months post-vaccine anti-S levels were significantly associated with having received three doses of the vaccine (RR = 2.45, CI = 1.92–3.13) and with having a prior COVID-19 infection (RR = 2.30, CI = 2.15–2.46). Conversely, lower levels were associated with higher age (RR = 0.94, CI = 0.91–0.96), more time since the last vaccine dose (RR = 0.95, CI = 0.94–0.96), and multimorbidity (RR = 0.89, CI = 0.80–1.00). Hypertension is significantly associated with lower anti-S levels (RR = 0.87, CI = 0.80–0.95). The serological response to vaccines is more inadequate in individuals with multimorbidity.
Published: 2023
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48. Erratum: Corrigendum: Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer

Author: Mari Nelis, Neil E. Caporaso, Tõnu Vooder, H. Bas Bueno-de-Mesquita, Ben Kinnersley, Frank Skorpen, Stephen J. Chanock, Mattias Johansson, Gary E. Goodman, Athena Matakidou, Kay-Tee Khaw, Amy Lloyd, Dana Mates, Neonilia Szeszenia-Dabrowska, Elisabete Weiderpass, Maiken Elvestad Gabrielsen, Paul Brennan, David C. Christiani, Maria Teresa Landi, Susan M. Gapstur, Yuanqing Ye, Andres Metspalu, Hendrik Dienemann, Nilanjan Chatterjee, Margaret R. Spitz, Younghun Han, Christopher I. Amos, James McKay, Manon Delahaye-Sourdeix, Lars J. Vatten, William Wheeler, Eleonora Fabianova, Daniel Chubb, Simone Benhamou, T. Eisen, Peter Rudnai, Chu Chen, Ghislaine Scelo, Antonio Agudo, Paolo Vineis, Marcin Lener, Mikael Johansson, Angela Risch, Maria Timofeeva, Mark Lathrop, Li Su, Yongyue Wei, Victoria L. Stevens, Peter Broderick, Maxime Vallée, Inger Njølstad, Rayjean J. Hung, David Zaridze, Thorunn Rafnar, Vladimir Janout, Yufei Wang, Jian Gu, Hans E. Krokan, Marc Henrion, Lenka Foretova, Kari Stefansson, Gudmar Thorleifsson, Demetrius Albanes, Patrick Sulem, Geoffrey Liu, Rudolf Kaaks, Marina Laplana, Jan Lubinski, Xuchen Zong, Vladimir Bencko, Elio Riboli, Zhaoming Wang, Françoise Clavel-Chapelon, Albert Rosenberger, Dimitrios Trichopoulos, Valerie Gaborieau, Florence Le Calvez-Kelm, Anne Tjønneland, Wei V. Chen, Jolanta Lissowska, Kristjan Välk, Richard S. Houlston, and Xifeng Wu
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Biology, Affect (psychology), medicine.disease, 3. Good health, 03 medical and health sciences, 030104 developmental biology, Internal medicine, Genetics, medicine, Lung cancer, CHEK2
Abstract: Nat. Genet. 46, 736–741 (2014); published online 1 June 2014; corrected after print 23 January 2017 In the version of this article initially published, the name of author Florence Le Calvez-Kelm appeared incorrectly as Florence LeCalvez-Kelm. The error has been corrected in the HTML and PDF versionsof the article.
Published: 2017

49. Determinants of anti-S immune response at 6 months after COVID-19 vaccination in a multicentric European cohort of healthcare workers – ORCHESTRA project

Author: Giulia Collatuzzo, Giovanni Visci, Francesco S. Violante, Stefano Porru, Gianluca Spiteri, Maria Grazia Lourdes Monaco, Francesca Larese Fillon, Corrado Negro, Christian Janke, Noemi Castelletti, Giuseppe De Palma, Emanuele Sansone, Dana Mates, Silvia Teodorescu, Eleonóra Fabiánová, Jana Bérešová, Luigi Vimercati, Silvio Tafuri, Mahsa Abedini, Giorgia Ditano, Shuffield S. Asafo, Paolo Boffetta, Orchestra WP5 Working Group, Carlotta Zunarelli, Roberta Bonfiglioli, Angela Carta, Giuseppe Verlato, Giuseppe Lippi, Davide Gibellini, Maria Diletta Pezzani, Lorena Torroni, Michael Hoelscher, Andreas Wieser, Christina Reinkemeyer, Michael Plank, Ivan Noreña, Raquel Rubio-Acero, Simon Winter, Mihaela Leustean, Ovidiu Perseca, Madalina Ipate, Agripina Rascu, Jozef Strhársky, Petra Hellebrandt, Daniela Križanová, Marianna Mrázová, Luigi De Maria, Stefania Sponselli, Pasquale Stefanizzi, and Antonio Caputi
Subjects: vaccine, COVID – 19, serology, health care workers (HCW), immune response, Immunologic diseases. Allergy, RC581-607
Abstract: BackgroundThe duration of immune response to COVID-19 vaccination is of major interest. Our aim was to analyze the determinants of anti-SARS-CoV-2 IgG titer at 6 months after 2-dose vaccination in an international cohort of vaccinated healthcare workers (HCWs).MethodsWe analyzed data on levels of anti-SARS-CoV-2 Spike antibodies and sociodemographic and clinical characteristics of 6,327 vaccinated HCWs from 8 centers from Germany, Italy, Romania and Slovakia. Time between 1st dose and serology ranged 150-210 days. Serological levels were log-transformed to account for the skewness of the distribution and normalized by dividing them by center-specific standard errors, obtaining standardized values. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of 1 standard deviation of log antibody level and corresponding 95% confidence interval (CI), and finally combined them in random-effects meta-analyses.ResultsA 6-month serological response was detected in 99.6% of HCWs. Female sex (RR 1.10, 95%CI 1.00-1.21), past infection (RR 2.26, 95%CI 1.73-2.95) and two vaccine doses (RR 1.50, 95%CI 1.22-1.84) predicted higher IgG titer, contrary to interval since last dose (RR for 10-day increase 0.94, 95%CI 0.91-0.97) and age (RR for 10-year increase 0.87, 95%CI 0.83-0.92). M-RNA-based vaccines (p
Published: 2022
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50. Abstract 3137: NGS-based detection of KRAS hotspot mutations in plasma cell-free DNA of pancreatic cancer cases

Author: Geoffroy Durand, Priscilia Chopard, Paul Brennan, Vladimir Janout, Eleonora Fabianova, Graham Byrnes, Ivana Holcatova, Maroulio Pertesi, James McKay, Matthieu Foll, Florence Le Calvez-Kelm, Ghislaine Scelo, Magdalena B. Wozniak, Lenka Foretova, Maxime Vallée, and Tiffany M. Delhomme
Subjects: Genetics, Cancer Research, Ion semiconductor sequencing, Biology, medicine.disease, medicine.disease_cause, Deep sequencing, 3. Good health, Minor allele frequency, Oncology, Pancreatic cancer, Cancer research, medicine, Pancreatitis, KRAS, Allele, Gene
Abstract: Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by hotspot mutations in the KRAS gene (codons 12, 13 or 61) in 85-90% of cases. Codon 12 KRAS mutations have been detected in pancreatic juice, blood and stool samples from pancreatic cancer cases and represent promising biomarkers for early detection. However, the proportion of tumor-derived KRAS mutations in cell-free DNA fragments (cfDNA) has shown large variations, probably because of the heterogeneity in biosamples and assays tested. Deep sequencing technologies (NGS) allow the identification of low-abundance somatic variants, but have not previously been applied to the detection of KRAS hotspot mutations in cfDNA of PDAC cases. Moreover, variant calling methods have rarely been tested against cancer-free individuals so the proportion of false positives is unknown. We investigated whether deep sequencing of KRAS mutations at codons 12, 13 and 61 in plasma samples could represent a robust assay to distinguish pancreatic cancer from chronic pancreatitis and healthy controls. Methods: We developed an Ion Torrent-based NGS KRAS assay (partial exons 2 and 3, totalling 208bp) to screen cfDNA from plasma samples of 461 PDAC cases, 154 individuals with chronic pancreatitis and 421 healthy controls. cfDNA extraction (>4ng) and sequencing (>1000x coverage on average, and absence of systematic high sequencing error rates on the 208bp) performed well on 431 (93%) PDAC cases, 138 (90%) chronic pancreatitis, and 388 (95%) controls. We fit a robust negative-binomial regression to estimate the distribution of the sequencing errors at each DNA bp position and identified outlying samples, which were considered as KRAS positive when q-value Results: Sequencing of the serial dilutions of KRAS p.G12V mutated DNA indicated a detection threshold at a minor allele frequency of 0.2%. KRAS mutations in cfDNA were detected in 83 (19.3%) PDAC cases (73 on codon 12; 8 on codon 61; 1 on codon 13; and 1 multiple codons, i.e., similar in proportions as reported in tumor tissue from the International Cancer Genomic Consortium); 3 (2.2%) chronic pancreatitis (all on codon 12); and 8 (2.1%) healthy controls (4 on codon 12 and 4 on codon 61). Stage was significantly associated with the proportion of detected mutations in cancer cases (chi-squared p = 0.0005): the proportions of cases with detectable KRAS mutations in plasma were 7.9%, 14.9%, and 31.1% for local, regional, and advanced stages, respectively. Conclusions: The NGS-based KRAS mutation screening is a sensitive approach to detect low allelic fraction in plasma cfDNA, although its utility for early detection is still limited. However, it has the capacity to identify specific KRAS mutations, which could be useful in a panel of other non-invasive biomarkers. Citation Format: Florence Le Calvez-Kelm, Matthieu Foll, Magdalena B. Wozniak, Geoffroy Durand, Priscilia Chopard, Maroulio Pertesi, Tiffany Delhomme, Ivana Holcatova, Lenka Foretova, Vladimir Janout, Eleonora Fabianova, Maxime P. Vallée, Paul Brennan, James D. McKay, Graham Byrnes, Ghislaine Scélo. NGS-based detection of KRAS hotspot mutations in plasma cell-free DNA of pancreatic cancer cases. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3137.
Published: 2016

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