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141 results on '"Vermeulen, R.C.H."'

101. Transient receptor potential genes, smoking, occupational exposures and cough in adults

Author

Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Smit, L.A., Kogevinas, M., Antó, J., Bouzigon, E., González, J.R., Le Moual, N., Kromhout, J., Carsin, A., Pin, I., Jarvis, D., Vermeulen, R.C.H., Janson, C., Heinrich, J., Gut, I., Lathrop, M., Valverde, M.A., Demenais, F., Kauffmann, F., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Smit, L.A., Kogevinas, M., Antó, J., Bouzigon, E., González, J.R., Le Moual, N., Kromhout, J., Carsin, A., Pin, I., Jarvis, D., Vermeulen, R.C.H., Janson, C., Heinrich, J., Gut, I., Lathrop, M., Valverde, M.A., Demenais, F., and Kauffmann, F.

Published
2012

103. 2-Naphthol levels and genotoxicity in rubber workers

Author

Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Talaska, G., Gaultney, B., Peters, S., Succop, P., Vermeulen, R.C.H., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Talaska, G., Gaultney, B., Peters, S., Succop, P., and Vermeulen, R.C.H.

Published
2012

104. Malignant mesothelioma and asbestos-related lung cancer: diagnosis, prognosis and burden

Author

Child Health, Circulatory Health, Infection & Immunity, JC onderzoeksprogramma Methodologie, Other research (not in main researchprogram), Cancer, General Practice & Nursing Science, Moons, KGM, de Mol, B.A.J.M., Koffijberg, Erik, Vermeulen, R.C.H., van der Bij, S., Child Health, Circulatory Health, Infection & Immunity, JC onderzoeksprogramma Methodologie, Other research (not in main researchprogram), Cancer, General Practice & Nursing Science, Moons, KGM, de Mol, B.A.J.M., Koffijberg, Erik, Vermeulen, R.C.H., and van der Bij, S.

Published
2012

105. Biomarkers in kidney damage

Author

Spierenburg, E.A.J., Vermeulen, R.C.H. (Thesis Advisor), Reiss, B., Spierenburg, E.A.J., Vermeulen, R.C.H. (Thesis Advisor), and Reiss, B.

Abstract

The aim of this review is to give a comprehensive overview of the current state of biomarkers and biomarker research in kidney damage. Kidneys play an important role in the maintenance of the physiologic balance in the body. It can therefore be very detrimental if the kidneys are damaged. Kidney injuries can be divided into to classes: acute and chronic kidney injury. Especially in acute kidney injury, early detection is essential for a successful treatment. Correct diagnosis of chronic forms of injury is very important. Standard biomarkers for kidney injury (e.g. serum creatinine levels) are non-specific and only detectable after at least several days after onset of kidney injury. Fortunately, new biomarkers are under development, which are very promising for clinical use as well as for research purposes.

Published
2011

107. Level of education and the risk of lymphoma in the European prospective investigation into cancer and nutrition.

Author

Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Hermann, S., Rohrmann, S., Linseisen, J., Nieters, A., Khan, A., Gallo, V., Overvad, K., Tjonneland, A., Raaschou-Nielsen, O., Bergmann, M.M., Boeing, H., Becker, N., Kaaks, R., Bueno-de-Mesquita, H.B., May, A.M., Vermeulen, R.C.H., Bingham, S, Khaw, K.T., Key, T.J., Travis, R.C., Trichopoulou, A., Georgila, C., Triantafylou, D., Celentano, E., Krogh, V., Masala, G., Tumino, R., Agudo, A., Altzibar, J.M., Ardanaz, E., Martinez-Garcia, C., Arguelles, M.V., Tormo, M.J., Braaten, T., Lund, E., Manjer, J., Zackrisson, S., Hallmans, G., Malmer, B., Boffetta, P., Brennan, P., Slimani, N., Vineis, P., Riboli, E., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Hermann, S., Rohrmann, S., Linseisen, J., Nieters, A., Khan, A., Gallo, V., Overvad, K., Tjonneland, A., Raaschou-Nielsen, O., Bergmann, M.M., Boeing, H., Becker, N., Kaaks, R., Bueno-de-Mesquita, H.B., May, A.M., Vermeulen, R.C.H., Bingham, S, Khaw, K.T., Key, T.J., Travis, R.C., Trichopoulou, A., Georgila, C., Triantafylou, D., Celentano, E., Krogh, V., Masala, G., Tumino, R., Agudo, A., Altzibar, J.M., Ardanaz, E., Martinez-Garcia, C., Arguelles, M.V., Tormo, M.J., Braaten, T., Lund, E., Manjer, J., Zackrisson, S., Hallmans, G., Malmer, B., Boffetta, P., Brennan, P., Slimani, N., Vineis, P., and Riboli, E.

Published
2010

108. Use of proteomics for the early diagnosis fo breast cancer

Author

JC onderzoeksprogramma Kanker, Cancer, Epidemiology & Health Economics, Beijnen, J.H., Peeters, Petra H.M., van Gils, CH, Vermeulen, R.C.H., van Winden, A.W.J., JC onderzoeksprogramma Kanker, Cancer, Epidemiology & Health Economics, Beijnen, J.H., Peeters, Petra H.M., van Gils, CH, Vermeulen, R.C.H., and van Winden, A.W.J.

Published
2010

109. Large-scale evaluation of candidate genes identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity.

Author

Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Dep Biologie, Lan, Q., Zhang, L., Shen, M., Jo, W.J., Vermeulen, R.C.H., Li, G., Vulpe, C., Lim, S.K., Ren, X., Rappaport, S.M., Berndt, S.I., Yeager, M., Yuenger, J., Hayes, R.B., Linet, M., Yin, S., Chanock, S., Smith, M.T., Rothman, N., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Dep Biologie, Lan, Q., Zhang, L., Shen, M., Jo, W.J., Vermeulen, R.C.H., Li, G., Vulpe, C., Lim, S.K., Ren, X., Rappaport, S.M., Berndt, S.I., Yeager, M., Yuenger, J., Hayes, R.B., Linet, M., Yin, S., Chanock, S., Smith, M.T., and Rothman, N.

Published
2009

110. Smoking and risk for amyotrophic lateral sclerosis: analysis of the EPIC cohort.

Author

Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Gallo, V., Bueno de Mesquita, H.B., Vermeulen, R.C.H., Andersen, P.M., Kyrozis, A., Linseisen, J., Kaaks, R., Allen, N.E., Roddam, A.W., Boshuizen, H.C., Peeters, P.H.M., Palli, D., Mattiello, A., Sieri, S., Tumino, R., Jimenez-Martin, J.M., Diaz, M.J., Suarez, L.R., Trichopoulou, A., Agudo, A., Arriola, L., Barricante-Gurrea, A., Bingham, S., Khaw, K.T., Manjer, J., Lindkvist, B., Overvad, K., Bach, F.W., Tjonneland, A., Olsen, A., Bergmann, M.M., Boeing, H., Clavel-Chapelon, F., Lund, E., Hallmans, G., Middleton, L., Vineis, P., Riboli, E., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Gallo, V., Bueno de Mesquita, H.B., Vermeulen, R.C.H., Andersen, P.M., Kyrozis, A., Linseisen, J., Kaaks, R., Allen, N.E., Roddam, A.W., Boshuizen, H.C., Peeters, P.H.M., Palli, D., Mattiello, A., Sieri, S., Tumino, R., Jimenez-Martin, J.M., Diaz, M.J., Suarez, L.R., Trichopoulou, A., Agudo, A., Arriola, L., Barricante-Gurrea, A., Bingham, S., Khaw, K.T., Manjer, J., Lindkvist, B., Overvad, K., Bach, F.W., Tjonneland, A., Olsen, A., Bergmann, M.M., Boeing, H., Clavel-Chapelon, F., Lund, E., Hallmans, G., Middleton, L., Vineis, P., and Riboli, E.

Published
2009

111. Changes in the peripheral blood transcriptome associated with occupational benzene exposure identified by cross-comparison on two microarray platforms.

Author

Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, McHale, C.M., Zhang, L., Lan, Q., Li, G., Hubbard, A.E., Forrest, M.S., Vermeulen, R.C.H., Chen, J., Shen, M., Rappaport, S.M., Yin, S., Smith, M.T., Rothman, N., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, McHale, C.M., Zhang, L., Lan, Q., Li, G., Hubbard, A.E., Forrest, M.S., Vermeulen, R.C.H., Chen, J., Shen, M., Rappaport, S.M., Yin, S., Smith, M.T., and Rothman, N.

Published
2009

112. Coal use, stove improvement, and adult pneumonia mortality in Xuanwei, China: a retrospective cohort study.

Author

Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Shen, M., Chapman, R.S., Vermeulen, R.C.H., Tian, L., Zheng, T., Chen, B.E., Engels, E.A., He, X., Blair, A., Lan, Q., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Shen, M., Chapman, R.S., Vermeulen, R.C.H., Tian, L., Zheng, T., Chen, B.E., Engels, E.A., He, X., Blair, A., and Lan, Q.

Published
2009

113. Determinants of urinary 1-hydroxypyrene glucuronide in South Korean children.

Author

Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Lee, K.H., Vermeulen, R.C.H., Lenters, V.C., Cho, S.H., Strickland, P., Kang, D., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Lee, K.H., Vermeulen, R.C.H., Lenters, V.C., Cho, S.H., Strickland, P., and Kang, D.

Published
2009

114. Exposure to atrazine and selected non-persistent pesticides among corn farmers during a growing season.

Author

Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Bakke, B., de Roos, A.J., Barr, D.B., Stewart, P.A., Blair, A., Freeman, L.B., Lynch, C.F., Allen, R.H., Alavanja, M.C., Vermeulen, R.C.H., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Bakke, B., de Roos, A.J., Barr, D.B., Stewart, P.A., Blair, A., Freeman, L.B., Lynch, C.F., Allen, R.H., Alavanja, M.C., and Vermeulen, R.C.H.

Published
2009

115. Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China.

Author

Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Shen, M., Vermeulen, R.C.H., Rajaraman, P., Menashe, I., He, X., Chapman, R.S., Yeager, M., Thomas, G., Burdett, L., Hutchinson, A., Yuenger, J., Chanock, S., Lan, Q., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Shen, M., Vermeulen, R.C.H., Rajaraman, P., Menashe, I., He, X., Chapman, R.S., Yeager, M., Thomas, G., Burdett, L., Hutchinson, A., Yuenger, J., Chanock, S., and Lan, Q.

Published
2009

116. Evidence that humans metabolize benzene via two pathways.

Author

Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Rappaport, S.M., Kim, S., Lan, Q., Vermeulen, R.C.H., Waidyanatha, S., Zhang, L., Li, G., Yin, S., Hayes, R.B., Rothman, N., Smith, M.T., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Rappaport, S.M., Kim, S., Lan, Q., Vermeulen, R.C.H., Waidyanatha, S., Zhang, L., Li, G., Yin, S., Hayes, R.B., Rothman, N., and Smith, M.T.

Published
2009

118. Early diagnostic protein biomarkers for breast cancer: how far have we come?

Author

Opstal - van Winden, A.W.J., Vermeulen, R.C.H., Peeters, P.H.M., Beijnen, J.H., van Gils, C.H., Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, and Sub Clinical Pharmacology

Subjects
Proteomics, Cancer Research, Protein biomarkers, Molecular Sequence Data, Proteinase Inhibitory Proteins, Secretory, Breast Neoplasms, Disease, Mass spectrometry, Bioinformatics, Breast cancer, medicine, Biomarkers, Tumor, Animals, Humans, Amino Acid Sequence, Early Detection of Cancer, Glycoproteins, Sample handling, business.industry, Blood Proteins, medicine.disease, Peptide Fragments, Matrix-assisted laser desorption/ionization, Oncology, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Complement C3a, Female, Breast cancer specific, business
Abstract

Many studies have used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to search for blood-based proteins that are related to the presence of breast cancer. We review the biomarkers discovered or targeted measured by these methods and discuss the strengths and weaknesses of these studies. We highlight two proteins that were most often related to breast cancer: C3a des-arginine anaphylatoxin (C3a(desArg)) (molecular weight: 8,938 Da) and fragments of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4). In addition, we elaborate on three important methodological aspects related to these studies: protein identification, specificity of the markers, and disease heterogeneity. Finally, we propose some points to be addressed in future studies. These include the use of other analytical measurement techniques, need of protein identification, the importance of identical sample handling protocols for cases and controls, and the stratification of the results according to molecular subtypes and stages of breast cancer. Ultimately this may lead to the discovery of new and valid breast cancer specific biomarkers.

Published
2012

120. Urinary pesticide mixture patterns and exposure determinants in the adult population from the Netherlands and Switzerland: Application of a suspect screening approach.

Author

Ottenbros, I.B., Ammann, P., Imboden, M., Fuhrimann, S., Zock, J.-P., Lebret, E., Vermeulen, R.C.H., Nijssen, R., Lommen, A., Mol, H., Vlaanderen, J.J., and Probst-Hensch, N.

Subjects
*PESTICIDES, *ORGANIC foods, *URINALYSIS, *AGRICULTURE
Abstract

Non-occupational sources of pesticide exposure may include domestic pesticide usage, diet, occupational exposure of household members, and agricultural activities in the residential area. We conducted a study with the ambition to characterize pesticide mixture patterns in a sample of the adult population of the Netherlands and Switzerland, using a suspect screening approach and to identify related exposure determinants. A total of 105 and 295 adults participated in the Dutch and Swiss studies, respectively. First morning void urine samples were collected and analyzed in the same laboratory. Harmonized questionnaires about personal characteristics, pesticide-related activities, and diet were administered. Detection rates and co-occurrence patterns were calculated to explore internal pesticide exposure patterns. Censored linear and logistic regression models were constructed to investigate the association between exposure and domestic pesticide usage, consumption of homegrown and organic foods, household members' exposure, and distance to agricultural and forest areas. From the 37 detected biomarkers, 3 (acetamiprid (-CH2), chlorpropham (4-HSA), and flonicamid (-C2HN)) were detected in ≥40% of samples. The most frequent combination of biomarkers (acetamiprid-flonicamid) was detected in 22 (5.5%) samples. Regression models revealed an inverse association between high organic vegetable and fruit consumption and exposure to acetamiprid, chlorpropham, propamocarb (+O), and pyrimethanil (+O + SO3). Within-individual correlations in repeated samples (summer/winter) from the Netherlands were low (≤0.3), and no seasonal differences in average exposures were observed in Switzerland. High consumption of organic fruit and vegetables was associated with lower pesticide exposure. In the two countries, detection rates and co-occurrence were typically low, and within-person variability was high. Our study results provide an indication for target biomarkers to include in future studies aimed at quantifying urinary exposure levels in European adult populations. [Display omitted] • Detection of numerous pesticide metabolites in single morning void urine samples. • Similar pesticide exposure patterns in NL and CH; higher detection frequency in NL. • Generally low detection rates and frequency of co-occurrence; no seasonal differences. • Most frequently detected metabolites from: acetamiprid, chlorpropham and flonicamid. • High consumption of organic fruit/vegetables potentially reduces pesticide exposure. [ABSTRACT FROM AUTHOR]

Published
2023
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121. Improving epidemiological studies on health effects from radiofrequency electromagnetic fields exposure

Author

Reedijk, Marije, Vermeulen, R.C.H., Kromhout, H., and University Utrecht

Subjects
radiofrequency electromagnetic fields, health, epidemiological studies, mobile phone, base stations, Parkinson's disease, symptoms, birth outcomes
Abstract

Everybody is exposed to radiofrequency electromagnetic fields (RF-EMF) in daily life, either by their own communications device(s) or by mobile phone base stations or radio transmitters in their living environment. There are still concerns about the potential health effects of RF-EMF among scientists and in society. This thesis addresses some of these uncertainties in RF-EMF epidemiology such as investigating the repeatability of self-reported use of mobile communication devices and improvement of exposure assessment of mobile phone use by combining self-reported and operator-recorded data. Furthermore we examined the role of perception besides modeled exposure for health symptoms. The first part of my thesis was about improving RF-EMF epidemiology by harmonizing and combining data from multiple prospective cohort studies and by evaluating and determining exposure assessment of RF-EMF by improving the accuracy of (self-reported) mobile phone use within the COSMOS study. We showed that combing different sources (self-reported and operator recorded) by regression calibration resulted in limited bias and outperformed other statistical methods such as complete-case and multiple imputation methods. Furthermore a case ascertainment method was developed to identify Parkinson’s Disease within two large prospective cohort studies (AMIGO and EPIC-NL). We included multiple information sources like registry data and self-reported data. We evaluated our developed likelihood score, existing of four categories, with known etiological risk factors of Parkinson’s Disease. For epidemiological studies for which no specific registry is available, as is the case for Parkinson’s Disease, it is important to combine multiple information sources to maximize sensitivity and specificity in the disease outcome measure. In the last part of this thesis we expanded the knowledge on possible health effects of RF-EMF. We found no effects with birth weight or fetal growth and maternal mobile phone use during pregnancy. However we found effects of shorter pregnancy duration and increased risk of preterm birth. We could not adjust for maternal stress in this study, although it has been shown to be an important confounder. Furthermore we investigated the impact of both modeled and perceived exposure to RF-EMF from mobile phone base stations, road traffic noise and air pollution on self-reported health outcomes. We used longitudinal data from the AMIGO cohort. Perceived exposures showed overall stronger associations with symptoms than modeled exposures. When both modeled and perceived exposure was included as predictors in a single model, the impact of modeled exposure on self-reported health outcomes disappeared or strongly diminished. This shows the importance of perceived exposures in certain health effects. This thesis showed that using multiple information sources for assessment of both exposure and health outcomes within epidemiological studies is feasible. The findings presented in this thesis will be input for future epidemiological analyses within COSMOS and for studies on Parkinson’s Disease and environmental exposures within the AMIGO and EPIC-NL cohorts. The methods proposed in this thesis could also be applied in other (environmental) epidemiological studies. Further integration of multiple sources of RF-EMF by integrative exposure assessment models in epidemiological studies is essential to get more definitive answers on potential effects of RF-EMF exposure.

Published
2022

122. Occupational exposure assessment in the general population: improvements, innovations, and impact

Author

Calvin Benjamin Ge, Vermeulen, R.C.H., Peters, S.M., and University Utrecht

Subjects
education.field_of_study, Occupational epidemiology, business.industry, Environmental health, Population, occupational exposure, exposure assessment, occupational epidemiology, lung cancer, diesel engine exhaust, silica, benzene, Medicine, Occupational exposure, business, education, Lung cancer, medicine.disease, Exposure assessment
Abstract

Studies performed in the general population are important for understanding the relationships between occupational exposures and human diseases. However, estimating occupational exposure in population-based studies is challenging due to various factors, including the large number of participants, variety of included occupations, and the lack of personalised exposure measurements. Through one systematic review and five original research studies, this thesis explores how existing studies estimated exposure in population-based studies, where potential improvements may exist for current approaches, what innovations may be on the horizon, and how these advances may be harvested for higher scientific and societal impact. Two important results from the thesis are highlighted in this summary. First, the thesis concludes that approaches used to estimate occupational exposures in population-based studies in the last 30 years have generally stayed the same. Fundamental innovations are hampered by the scarcity of exposure information in population-based studies, which are inferred from subject responses to questionnaires on their work history. However, a key area of potential advancement exists in using artificial intelligence and natural language processing to automate, standardise, and adaptively improve how we obtain and process exposure-related information from study subjects. Second, by applying quantitatively estimated exposures in population-based studies, this thesis reports that work exposures to crystalline silica and diesel engine exhaust, even at relatively low levels, were associated with increased risks of lung cancer. The numbers of additional lung cancer deaths associated with different exposure scenarios were calculated to make the results directly applicable for informing risk assessment and policymaking.

Published
2021

123. Genetically Determined Height and Risk of Non-hodgkin Lymphoma

Author

Amy Moore, Eleanor Kane, Zhaoming Wang, Orestis A. Panagiotou, Lauren R. Teras, Alain Monnereau, Nicole Wong Doo, Mitchell J. Machiela, Christine F. Skibola, Susan L. Slager, Gilles Salles, Nicola J. Camp, Paige M. Bracci, Alexandra Nieters, Roel C. H. Vermeulen, Joseph Vijai, Karin E. Smedby, Yawei Zhang, Claire M. Vajdic, Wendy Cozen, John J. Spinelli, Henrik Hjalgrim, Graham G. Giles, Brian K. Link, Jacqueline Clavel, Alan A. Arslan, Mark P. Purdue, Lesley F. Tinker, Demetrius Albanes, Giovanni M. Ferri, Thomas M. Habermann, Hans-Olov Adami, Nikolaus Becker, Yolanda Benavente, Simonetta Bisanzi, Paolo Boffetta, Paul Brennan, Angela R. Brooks-Wilson, Federico Canzian, Lucia Conde, David G. Cox, Karen Curtin, Lenka Foretova, Susan M. Gapstur, Hervé Ghesquières, Martha Glenn, Bengt Glimelius, Rebecca D. Jackson, Qing Lan, Mark Liebow, Marc Maynadie, James McKay, Mads Melbye, Lucia Miligi, Roger L. Milne, Thierry J. Molina, Lindsay M. Morton, Kari E. North, Kenneth Offit, Marina Padoan, Alpa V. Patel, Sara Piro, Vignesh Ravichandran, Elio Riboli, Silvia de Sanjose, Richard K. Severson, Melissa C. Southey, Anthony Staines, Carolyn Stewart, Ruth C. Travis, Elisabete Weiderpass, Stephanie Weinstein, Tongzhang Zheng, Stephen J. Chanock, Nilanjan Chatterjee, Nathaniel Rothman, Brenda M. Birmann, James R. Cerhan, Sonja I. Berndt, Moore A., Kane E., Wang Z., Panagiotou O.A., Teras L.R., Monnereau A., Wong Doo N., Machiela M.J., Skibola C.F., Slager S.L., Salles G., Camp N.J., Bracci P.M., Nieters A., Vermeulen R.C.H., Vijai J., Smedby K.E., Zhang Y., Vajdic C.M., Cozen W., Spinelli J.J., Hjalgrim H., Giles G.G., Link B.K., Clavel J., Arslan A.A., Purdue M.P., Tinker L.F., Albanes D., Ferri G.M., Habermann T.M., Adami H.-O., Becker N., Benavente Y., Bisanzi S., Boffetta P., Brennan P., Brooks-Wilson A.R., Canzian F., Conde L., Cox D.G., Curtin K., Foretova L., Gapstur S.M., Ghesquieres H., Glenn M., Glimelius B., Jackson R.D., Lan Q., Liebow M., Maynadie M., McKay J., Melbye M., Miligi L., Milne R.L., Molina T.J., Morton L.M., North K.E., Offit K., Padoan M., Patel A.V., Piro S., Ravichandran V., Riboli E., de Sanjose S., Severson R.K., Southey M.C., Staines A., Stewart C., Travis R.C., Weiderpass E., Weinstein S., Zheng T., Chanock S.J., Chatterjee N., Rothman N., Birmann B.M., Cerhan J.R., and Berndt S.I.

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Chronic lymphocytic leukemia, Follicular lymphoma, diffuse large B-cell lymphoma, Single-nucleotide polymorphism, Genome-wide association study, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, follicular lymphoma, immune system diseases, Internal medicine, hemic and lymphatic diseases, Genetics, Medicine, Leucèmia limfocítica crònica, genetics, Original Research, Genetic association, Cancer och onkologi, business.industry, non-Hodgkin lymphoma, Odds ratio, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, marginal zone lymphoma, Lymphoma, Malaltia de Hodgkin, 030104 developmental biology, Cancer and Oncology, 030220 oncology & carcinogenesis, polygenic risk score, diffuse large B-celllymphoma, chronic lymphocytic leukemia, Hodgkin's disease, genetic, business, Diffuse large B-cell lymphoma, Genètica, height
Abstract

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00–1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01–1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.

Published
2020

124. Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

Author

Paul Brennan, M. G. Ennas, Qing Lan, Sasha Bernatsky, Alan A. Arslan, Peter Kraft, Lohith Madireddy, Roel Vermeulen, Kenan Onel, Graham G. Giles, John J. Spinelli, Eleanor Kane, Bengt Glimelius, Alexandra Nieters, David V. Conti, Christine F. Skibola, Pouya Khankhanian, Amy Moore, Ruth C. Travis, Mads Melbye, Sonja I. Berndt, Mark Liebow, Lauren R. Teras, Pierluigi Cocco, Lennox Din, Alain Monnereau, Mark P. Purdue, Lenka Foretova, Stephen J. Chanock, Stephen M. Ansell, Angela Brooks-Wilson, Wendy Cozen, Kenneth Offit, Demetrius Albanes, Anne J. Novak, Melissa C. Southey, Paolo Boffetta, Nicola J. Camp, James R. Cerhan, Rudolph Kaaks, Silvia de Sanjosé, Karen Curtin, Sophia S. Wang, James McKay, Nicole Wong Doo, Hans-Olov Adami, Tongzhang Zheng, Claire M. Vajdic, Nisha Pradhan, Giacomo Muzi, Gilles Salles, Nathaniel Rothman, Yolanda Benavente, Marc Maynadié, Brian K. Link, Delphine Casabonne, Hervé Ghesquières, Joseph Vijai, Karin E. Smedby, Paige M. Bracci, David G. Cox, Brenda M. Birmann, Lucia Miligi, Carolyn Stewart, Lucia Conde, Leonid Padyukov, Eve Roman, Richard K. Severson, Jorge R. Oksenberg, Immaculata De Vivo, Yawei Zhang, Corrado Magnani, Jacqueline Clavel, Lindsay M. Morton, Corinne Haioun, Jonathan N. Hofmann, Karen H. Costenbader, Pierre-Antoine Gourraud, Mohammad Sheikh, Stephanie J. Weinstein, Susan L. Slager, Paolo Vineis, Nikitha Kosaraju, Zachary Taub, Henrik Hjalgrim, Roger L. Milne, Morris Din, Martha Glenn, Nikolaus Becker, Timothy J. Vyse, Thomas M. Mack, Anthony Staines, Department of Medicine, Clinical Epidemiology, McGill University Health Center [Montreal] (MUHC), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Emory University [Atlanta, GA], Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, International Agency for Cancer Research (IACR), Department of Public Health, Vientiane Municipality, Registre des hémopathies malignes de Côte d'Or, Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, GRAPHOS - IFROSS Recherche, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Faculty of Medicine, Section of Rheumatology, Imperial College London, Karolinska Institutet [Stockholm], Epidémiologie environnementale des cancers, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], Uppsala Universitet [Uppsala], Carver College of Medicine, University of Iowa, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Division of Cancer Epidemiology and Genetics, National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Health Sciences, University of York [York, UK], Service de Radio-Oncologie [Lyon], Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), University of Melbourne, Centre Léon Bérard [Lyon], Mayo Clinic [Rochester], Occupational and Environmental Epidemiology Branch [Bethesda, Maryland], Division of Cancer Epidemiology and Genetics [Bethesda, Maryland], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), Memorial Sloane Kettering Cancer Center [New York], Huntsman Cancer Institute, Clinical Genetics Service, ISPO - Cancer Prevention and Research Institute, Unit of Environmental and Occupational Epidemiology, Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], B.B. Brodie Department of Neuroscience, Department of Pathology, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Unit of Environment Cancer Epidemiology, IARC, University of Torino and CPO-Piemonte, Università degli studi di Torino (UNITO), Department of Epidemiology, Harvard School of Public Health, Wayne State University [Detroit], Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Cancer Epidemiology Centre, Cancer Council Victoria, Cancer Epidemiology Unit, University of Oxford [Oxford], De la Molécule aux Nanos-objets : Réactivité, Interactions et Spectroscopies (MONARIS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Catalan Institute of Oncology (ICO), Department of Neurology [San Francisco, CA, USA], University of California [San Francisco] (UCSF), University of California-University of California, Norris Comprehensive Cancer Center, Masaryk University [Brno] (MUNI), Università degli studi di Torino = University of Turin (UNITO), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Imperial College London, University of Oxford, Din L., Sheikh M., Kosaraju N., Smedby K.E., Bernatsky S., Berndt S.I., Skibola C.F., Nieters A., Wang S., McKay J.D., Cocco P., Maynadie M., Foretova L., Staines A., Mack T.M., de Sanjose S., Vyse T.J., Padyukov L., Monnereau A., Arslan A.A., Moore A., Brooks-Wilson A.R., Novak A.J., Glimelius B., Birmann B.M., Link B.K., Stewart C., Vajdic C.M., Haioun C., Magnani C., Conti D.V., Cox D.G., Casabonne D., Albanes D., Kane E., Roman E., Muzi G., Salles G., Giles G.G., Adami H.-O., Ghesquieres H., De Vivo I., Clavel J., Cerhan J.R., Spinelli J.J., Hofmann J., Vijai J., Curtin K., Costenbader K.H., Onel K., Offit K., Teras L.R., Morton L., Conde L., Miligi L., Melbye M., Ennas M.G., Liebow M., Purdue M.P., Glenn M., Southey M.C., Din M., Rothman N., Camp N.J., Wong Doo N., Becker N., Pradhan N., Bracci P.M., Boffetta P., Vineis P., Brennan P., Kraft P., Lan Q., Severson R.K., Vermeulen R.C.H., Milne R.L., Kaaks R., Travis R.C., Weinstein S.J., Chanock S.J., Ansell S.M., Slager S.L., Zheng T., Zhang Y., Benavente Y., Taub Z., Madireddy L., Gourraud P.-A., Oksenberg J.R., Cozen W., Hjalgrim H., Khankhanian P., and Le Bihan, Sylvie

Subjects
Oncology, Male, Multifactorial Inheritance, Lymphoma, Epidemiology, Chronic lymphocytic leukemia, Follicular lymphoma, Genome-wide association study, Disease, Neurodegenerative, meta-analysi, immune system diseases, HLA Antigens, Risk Factors, hemic and lymphatic diseases, 2.1 Biological and endogenous factors, HLA Antigen, Aetiology, Genetics (clinical), Cancer, Allele, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Lymphoma, Non-Hodgkin, non-Hodgkin lymphoma, 030305 genetics & heredity, Single Nucleotide, Hematology, Middle Aged, 3. Good health, Public Health and Health Services, Female, Human, medicine.medical_specialty, autoimmune disease, genome-wide association study, meta-analysis, Alleles, Autoimmune Diseases, Humans, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Non-Hodgkin, Article, 03 medical and health sciences, Rare Diseases, Internal medicine, Genetic variation, medicine, Genetics, Polymorphism, 030304 developmental biology, Autoimmune disease, business.industry, Multiple sclerosis, Risk Factor, Arthritis, Inflammatory and immune system, Human Genome, medicine.disease, Brain Disorders, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

Published
2019

125. Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

Author

Mariagrazia Zucca, Thomas M. Habermann, Lauren R. Teras, Joseph Vijai, Lenka Foretova, Simon Crouch, Anneclaire J. De Roos, Jacqueline Clavel, Lindsay M. Morton, Melissa C. Southey, W. Ryan Diver, Patrick M. Gaffney, James McKay, Eve Roman, Sophia S. Wang, Mark P. Purdue, Hans-Olov Adami, Gilles Salles, Jarmo Virtamo, Yan W. Asmann, Angela Brooks-Wilson, Thierry Jo Molina, Andrew D. Zelenetz, Ahmet Dogan, Kenneth Offit, Peter Kraft, Gianluca Severi, Zhaoming Wang, Tongzhang Zheng, Sonja I. Berndt, Brian K. Link, Sasha Bernatsky, Theodore R. Holford, Emanuele Angelucci, Paige M. Bracci, Martyn T. Smith, Stephen J. Chanock, Brenda M. Birmann, Hervé Ghesquières, Stephen M. Ansell, Paolo Vineis, Mads Melbye, Kari E. North, Jenny Turner, Jacques Riby, Charles E. Lawrence, Alain Monnereau, Nikolaus Becker, Lucia Conde, James R. Cerhan, Susan L. Slager, Demetrius Albanes, Henrik Hjalgrim, Hervé Tilly, Héctor A. Velásquez García, Rebecca D. Jackson, Ann E. Clarke, Elizabeth A. Holly, Robert J. Klein, Paolo Boffetta, Mark Liebow, Karin E. Smedby, Marco Rais, David G. Cox, Patricia Hartge, Rosalind Ramsey-Goldman, Rachel S. Kelly, Lesley F. Tinker, Christine F. Skibola, Wendy Cozen, Tracy Lightfoot, Anne J. Novak, Heiner Boeing, Roel Vermeulen, Claire M. Vajdic, Bengt Glimelius, Kimberly A. Bertrand, Marc Maynadie, Eleanor Kane, Nathaniel Rothman, Yolanda Benavente, Paul Brennan, Anne Tjønneland, John J. Spinelli, Qing Lan, Anne Kricker, Alex Smith, Anthony Staines, Graham G. Giles, Carrie A. Thompson, Thomas E. Witzig, Stephanie J. Weinstein, Karen H. Cotenbader, Corinne Haioun, Anne Zeleniuch-Jacquotte, Simonetta Di Lollo, Alexandra Nieters, Rudolph Kaaks, Silvia de Sanjosé, Richard K. Severson, Yawei Zhang, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Oklahoma Medical Research Foundation, Registre des hémopathies malignes de Côte d'Or, Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Université Bourgogne Franche-Comté ( UBFC ), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), University of Calgary, Bernatsky, S. and García, H.A.V. and Spinelli, J.J. and Gaffney, P. and Smedby, K.E. and Ramsey-Goldman, R. and Wang, S.S. and Adami, H.-O. and Albanes, D. and Angelucci, E. and Ansell, S.M. and WAsmann, Y. and Becker, N. and Benavente, Y. and Berndt, S.I. and Bertrand, K.A. and Birmann, B.M. and Boeing, H. and Boffetta, P. and Bracci, P.M. and Brennan, P. and Brooks-Wilson, A.R. and Cerhan, J.R. and Chanock, S.J. and Clavel, J. and Conde, L. and Cotenbader, K.H. and Cox, D.G. and Cozen, W. and Crouch, S. and De Roos, A.J. and De Sanjose, S. and Di Lollo, S. and Diver, W.R. and Dogan, A. and Foretova, L. and Ghesquières, H. and Giles, G.G. and Glimelius, B. and Habermann, T.M. and Haioun, C. and Hartge, P. and Hjalgrim, H. and Holford, T.R. and Holly, E.A. and Jackson, R.D. and Kaaks, R. and Kane, E. and Kelly, R.S. and Klein, R.J. and Kraft, P. and Kricker, A. and Lan, Q. and Lawrence, C. and Liebow, M. and Lightfoot, T. and Link, B.K. and Maynadie, M. and McKay, J. and Melbye, M. and Molina, T.J. and Monnereau, A. and Morton, L.M. and Nieters, A. and North, K.E. and Novak, A.J. and Offit, K. and Purdue, M.P. and Rais, M. and Riby, J. and Roman, E. and Rothman, N. and Salles, G. and Severi, G. and Severson, R.K. and Skibola, C.F. and Slager, S.L. and Smith, A. and Smith, M.T. and Southey, M.C. and Staines, A. and Teras, L.R. and Thompson, C.A. and Tilly, H. and Tinker, L.F. and Tjonneland, A. and Turner, J. and Vajdic, C.M. and Vermeulen, R.C.H. and Vijai, J. and Vineis, P. and Virtamo, J. and Wang, Z. and Weinstein, S. and Witzig, T.E. and Zelenetz, A. and Zeleniuch-Jacquotte, A. and Zhang, Y. and Zheng, T. and Zucca, M. and Clarke, A.E., McGill University Health Center [Montreal] (MUHC), Oklahoma Medical Research Foundation (OMRF), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-2, and dIRAS RA-I&I RA

Subjects
Oncology, medicine.medical_specialty, Immunology, Single-nucleotide polymorphism, Genome-wide association study, [SDV.CAN]Life Sciences [q-bio]/Cancer, lymphoma, Human leukocyte antigen, Bioinformatics, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Internal medicine, medicine, SNP, 030203 arthritis & rheumatology, Systemic lupus erythematosus, business.industry, General Medicine, medicine.disease, Systemic lupus, Lupus Nephritis, Risk of diffuse large B-cell lymphoma, 3. Good health, Lymphoma, 030220 oncology & carcinogenesis, business, Diffuse large B-cell lymphoma, IRF5, malignancy
Abstract

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genomewide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE. © 2017 BMJ Publishing Group. All rights reserved.

Published
2017

126. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Author

Law, Philip J, Berndt, Sonja I, Speedy, Helen E, Camp, Nicola J, Sava, Georgina P, Skibola, Christine F, Holroyd, Amy, Vijai, Joseph, Sunter, Nicola J, Nieters, Alexandra, Bea, Silvia, Pettitt, AR, Monnereau, Alain, Martin-Garcia, David, Goldin, Lynn R, Clot, Guillem, Teras, Lauren R, Quintela, Inés, Birmann, Brenda M, Jayne, Sandrine J, Cozen, Wendy, Majid, Aneela, Smedby, Karin E, Lan, Qing, Dearden, Claire, Brooks-Wilson, Angela R, Hall, Andrew G, Purdue, Mark P, Mainou-Fowler, Tryfonia, Vajdic, Claire M, Jackson, Graham H, Cocco, Pierluigi, Marr, Helen, Zhang, Yawei, Zheng, Tongzhang, Giles, Graham G, Lawrence, Charles, Call, Timothy G, Liebow, Mark, Melbye, Mads, Glimelius, Bengt, Mansouri, Larry, Glenn, Martha, Curtin, Karen, Diver, W Ryan, Link, Brian K, Conde, Lucia, Bracci, Paige M, Holly, Elizabeth A, Jackson, Rebecca D, Tinker, Lesley F, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Maynadie, Marc, Mckay, James, Albanes, Demetrius, Weinstein, Stephanie, Wang, Zhaoming, Caporaso, Neil E, Morton, Lindsay M, Severson, Richard K, Riboli, Elio, Vineis, Paolo, Vermeulen, Roel CH, Southey, Melissa C, Milne, Roger L, Clavel, Jacqueline, Topka, Sabine, Spinelli, John J, Kraft, Peter, Ennas, Maria Grazia, Summerfield, Geoffrey, Ferri, Giovanni M, Harris, Robert J, Miligi, Lucia, Pettitt, Andrew R, North, Kari E, Allsup, David J, Fraumeni, Joseph F, Bailey, James R, Offit, Kenneth, Pratt, Guy, Hjalgrim, Henrik, Pepper, Chris, Chanock, Stephen J, Fegan, Chris, Rosenquist, Richard, Sanjose, Silvia de, Carracedo, Angel, Dyer, Martin JS, Catovsky, Daniel, Campo, Elias, Cerhan, James R, Allan, James M, Rothman, Nathanial, Houlston, Richard, Slager, Susan, Law, P.J., Berndt, S.I., Speedy, H.E., Camp, N.J., Sava, G.P., Skibola, C.F., Holroyd, A., Joseph, V., Sunter, N.J., Nieters, A., Bea, S., Monnereau, A., Martin-Garcia, D., Goldin, L.R., Clot, G., Teras, L.R., Quintela, I., Birmann, B.M., Jayne, S., Cozen, W., Majid, A., Smedby, K.E., Lan, Q., Dearden, C., Brooks-Wilson, A.R., Hall, A.G., Purdue, M.P., Mainou-Fowler, T., Vajdic, C.M., Jackson, G.H., Cocco, P., Marr, H., Zhang, Y., Zheng, T., Giles, G.G., Lawrence, C., Call, T.G., Liebow, M., Melbye, M., Glimelius, B., Mansouri, L., Glenn, M., Curtin, K., Diver, W.R., Link, B.K., Conde, L., Bracci, P.M., Holly, E.A., Jackson, R.D., Tinker, L.F., Benavente, Y., Boffetta, P., Brennan, P., Maynadie, M., McKay, J., Albanes, D., Weinstein, S., Wang, Z., Caporaso, N.E., Morton, L.M., Severson, R.K., Riboli, E., Vineis, P., Vermeulen, R.C.H., Southey, M.C., Milne, R.L., Clavel, J., Topka, S., Spinelli, J.J., Kraft, P., Ennas, M.G., Summerfield, G., Ferri, G.M., Harris, R.J., Miligi, L., Pettitt, A.R., North, K.E., Allsup, D.J., Fraumeni, J.F., Jr., Bailey, J.R., Offit, K., Pratt, G., Hjalgrim, H., Pepper, C., Chanock, S.J., Fegan, C., Rosenquist, R., De Sanjose, S., Carracedo, A., Dyer, M.J.S., Catovsky, D., Campo, E., Cerhan, J.R., Allan, J.M., Rothman, N., Houlston, R., and Slager, S.

Subjects
Lymphocytic leukaemia
Abstract

Several chronic 14175 lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10-13), 1q42.13 (rs41271473, P=1.06 × 10-10), 4q24 (rs71597109, P=1.37 × 10 -10), 4q35.1 (rs57214277, P=3.69 × 10-8), 6p21.31 (rs3800461, P=1.97 × 10-8), 11q23.2 (rs61904987, P=2.64 × 10-11), 18q21.1 (rs1036935, P=3.27 × 10-8), 19p13.3 (rs7254272, P=4.67 × 10-8) and 22q13.33 (rs140522, P=2.70 × 10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.

Published
2017

127. Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region

Author

Joseph Vijai, W. Ryan Diver, Degui Zhi, Brenda M. Birmann, Henrik Hjalgrim, Bruce K. Armstrong, Gianluca Severi, Pierluigi Cocco, Joseph F. Fraumeni, Xifeng Wu, Graham G. Giles, Eleanor Kane, Herve Ghesquieres, Eve Roman, Edward Giovannucci, Mads Melbye, Rudolph Kaaks, Lindsay M. Morton, Nicholas K. Akers, Elizabeth A. Holly, Liming Liang, Patrizio Mazza, Kari E. North, John J. Spinelli, Carrie A. Thompson, Bodil Ohlsson, Yuanqing Ye, Anneclaire J. De Roos, Stephen J. Chanock, Theodore R. Holford, Paul Brennan, Jianjun Liu, Roel Vermeulen, Thomas E. Witzig, Angela Brooks-Wilson, Mark P. Purdue, Ahmet Dogan, Gilles Salles, Kenneth Offit, Lucia Conde, Laurie Burdett, George J. Weiner, Anne Kricker, James McKay, Peter Kraft, Sonja I. Berndt, Attilio Gabbas, Rebecca Montalvan, Rebecca D. Jackson, Baoshan Ma, Zhaoming Wang, Patricia Hartge, Danylo J. Villano, Marc Maynadie, Mortimer J. Lacher, Lauren R. Teras, Susan L. Slager, Lenka Foretova, Rachel S. Kelly, Martha S. Linet, Brian K. Link, Jarmo Virtamo, Charles C. Chung, Anne Zeleniuch-Jacquotte, Martyn T. Smith, Tracy Lightfoot, Jacques Riby, Paolo Boffetta, Meredith Yeager, Brian C.-H. Chiu, Grzegorz S. Nowakowski, Yolanda Benavente, Bengt Glimelius, Mark Liebow, Saioa Chamosa, Charles E. Lawrence, Karin E. Smedby, Nikolaus Becker, Thomas M. Habermann, Jacqueline Clavel, Qing Lan, Alexandra Nieters, Maryjean Schenk, Sophia S. Wang, Demetrius Albanes, Lesley F. Tinker, Alex Smith, Anthony Staines, Amy Hutchinson, Wendy Cozen, Hans-Olov Adami, Anne J. Novak, Christine F. Skibola, Ann Maria, Elisabete Weiderpass, Kimberly A. Bertrand, James R. Cerhan, Maria Grazia Ennas, Claire M. Vajdic, Jinyan Huang, Paul I.W. de Bakker, Paige M. Bracci, Tongzhang Zheng, Ruth C. Travis, Paolo Vineis, Jia Nee Foo, Jennifer Turner, Alain Monnereau, Silvia de Sanjosé, Nathaniel Rothman, Yawei Zhang, Jian Gu, Skibola, C.F., Berndt, S.I., Vijai, J., Conde, L., Wang, Z., Yeager, M., De Bakker, P.I.W., Birmann, B.M., Vajdic, C.M., Foo, J.-N., Bracci, P.M., Vermeulen, R.C.H., Slager, S.L., De Sanjose, S., Wang, S.S., Linet, M.S., Salles, G., Lan, Q., Severi, G., Hjalgrim, H., Lightfoot, T., Melbye, M., Gu, J., Ghesquières, H., Link, B.K., Morton, L.M., Holly, E.A., Smith, A., Tinker, L.F., Teras, L.R., Kricker, A., Becker, N., Purdue, M.P., Spinelli, J.J., Zhang, Y., Giles, G.G., Vineis, P., Monnereau, A., Bertrand, K.A., Albanes, D., Zeleniuch-Jacquotte, A., Gabbas, A., Chung, C.C., Burdett, L., Hutchinson, A., Lawrence, C., Montalvan, R., Liang, L., Huang, J., Ma, B., Liu, J., Adami, H.-O., Glimelius, B., Ye, Y., Nowakowski, G.S., Dogan, A., Thompson, C.A., Habermann, T.M., Novak, A.J., Liebow, M., Witzig, T.E., Weiner, G.J., Schenk, M., Hartge, P., De Roos, A.J., Cozen, W., Zhi, D., Akers, N.K., Riby, J., Smith, M.T., Lacher, M., Villano, D.J., Maria, A., Roman, E., Kane, E., Jackson, R.D., North, K.E., Diver, W.R., Turner, J., Armstrong, B.K., Benavente, Y., Boffetta, P., Brennan, P., Foretova, L., Maynadie, M., Staines, A., McKay, J., Brooks-Wilson, A.R., Zheng, T., Holford, T.R., Chamosa, S., Kaaks, R., Kelly, R.S., Ohlsson, B., Travis, R.C., Weiderpass, E., Clavel, J., Giovannucci, E., Kraft, P., Virtamo, J., Mazza, P., Cocco, P., Ennas, M.G., Chiu, B.C.H., Fraumeni, J.F., Jr., Nieters, A., Offit, K., Wu, X., Cerhan, J.R., Smedby, K.E., Chanock, S.J., and Rothman, N.

Subjects
EXPRESSION, Follicular lymphoma, Single-nucleotide polymorphism, Genome-wide association study, Human leukocyte antigen, Biology, VARIANTS, Polymorphism, Single Nucleotide, follicular lymphoma, HLA Antigens, Polymorphism (computer science), Report, CLASS-I, RESOURCE, Biomarkers, Tumor, Genetics, medicine, Chromosomes, Human, Humans, TOOL, Genetic Predisposition to Disease, Genetics(clinical), PEPTIDE, Allele, Lymphoma, Follicular, Alleles, Genetics (clinical), Genetic association, SNPS, RISK, Genome-wide association, Haplotype, medicine.disease, HLA, Haplotypes, Case-Control Studies, UNIVERSITY, SET, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10 -20) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10 -11) near ETS1; 3q28 (rs6444305, p = 1.10 × 10 -10) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10 -10) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10 -8) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRß1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10 -67 to 2.67 × 10 -70). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 × 10 -16) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 × 10 -9). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk. © 2014 by The American Society of Human Genetics. All rights reserved.

Published
2016

128. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

Author

Henrik Hjalgrim, Joseph Vijai, Bengt Glimelius, Kimberly A. Bertrand, Immaculata De Vivo, Eve Roman, Martha Glenn, Nathaniel Rothman, Yolanda Benavente, Zhaoming Wang, Ju-Hyun Park, Anneclaire J. De Roos, John J. Spinelli, Demetrius Albanes, Paul Brennan, Emanuele Angelucci, Mariagrazia Zucca, Qing Lan, Kari E. North, Paige M. Bracci, Mark P. Purdue, Marco Rais, Melissa C. Southey, Alain Monnereau, Ahmet Dogan, Graham G. Giles, Robert J. Klein, Peter Kraft, Lesley F. Tinker, Laurie Burdett, Lucia Conde, Carrie A. Thompson, James McKay, Martyn T. Smith, Göran Roos, Yan W. Asmann, Dennis D. Weisenburger, Elizabeth A. Holly, Thomas E. Witzig, Liming Liang, Paul I.W. de Bakker, Alex Smith, Jarmo Virtamo, Charles E. Lawrence, Patricia Hartge, Karen Curtin, Anthony Staines, Nikolaus Becker, Nicola J. Camp, Charles C. Chung, Degui Zhi, Brenda M. Birmann, W. Ryan Diver, Roel Vermeulen, Sonja I. Berndt, Tongzhang Zheng, Silvia de Sanjosé, Eleanor Kane, James R. Cerhan, Christopher R. Flowers, Joseph F. Fraumeni, Stephen J. Chanock, Stephen M. Ansell, Angela Brooks-Wilson, Kenneth Offit, Jinyan Huang, Mads Melbye, Edward Giovannucci, Baoshan Ma, Tracy Lightfoot, Brian K. Link, Richard K. Severson, Theodore R. Holford, Yawei Zhang, Anne Tjønneland, Meredith Yeager, Wendy Cozen, Anne J. Novak, Lauren R. Teras, Claire M. Vajdic, Lisa A. Cannon-Albright, Lenka Foretova, Christine F. Skibola, Sophia S. Wang, Hans-Olov Adami, Andrew D. Zelenetz, Jenny Turner, Paolo Vineis, Corinne Haioun, Hervé Tilly, Anne Zeleniuch-Jacquotte, Thomas M. Habermann, Paolo Boffetta, Jacqueline Clavel, Herve Ghesquieres, Stephanie J. Weinstein, Lindsay M. Morton, Susan L. Slager, Simon Crouch, Gilles Salles, Rachel S. Kelly, Karin E. Smedby, Amy Hutchinson, David G. Cox, Elio Riboli, Jacques Riby, Rebecca D. Jackson, Mark Liebow, Thierry Jo Molina, Danylo J. Villano, Marc Maynadie, Yuanqing Ye, Heiner Boeing, Jian Gu, Brian C.-H. Chiu, Simonetta Di Lollo, Mitchell J. Machiela, Alexandra Nieters, Xifeng Wu, Rudolph Kaaks, Machiela, M.J., Lan, Q., Slager, S.L., Vermeulen, R.C.H., Teras, L.R., Camp, N.J., Cerhan, J.R., Spinelli, J.J., Wang, S.S., Nieters, A., Vijai, J., Yeager, M., Wang, Z., Ghesquières, H., McKay, J., Conde, L., de Bakker, P.I.W., Cox, D.G., Burdett, L., Monnereau, A., Flowers, C.R., De Roos, A.J., Brooks-Wilson, A.R., Giles, G.G., Melbye, M., Gu, J., Jackson, R.D., Kane, E., Purdue, M.P., Vajdic, C.M., Albanes, D., Kelly, R.S., Zucca, M., Bertrand, K.A., Zeleniuch-Jacquotte, A., Lawrence, C., Hutchinson, A., Zhi, D., Habermann, T.M., Link, B.K., Novak, A.J., Dogan, A., Asmann, Y.W., Liebow, M., Thompson, C.A., Ansell, S.M., Witzig, T.E., Tilly, H., Haioun, C., Molina, T.J., Hjalgrim, H., Glimelius, B., Adami, H.-O., Roos, G., Bracci, P.M., Riby, J., Smith, M.T., Holly, E.A., Cozen, W., Hartge, P., Morton, L.M., Severson, R.K., Tinker, L.F., North, K.E., Becker, N., Benavente, Y., Boffetta, P., Brennan, P., Foretova, L., Maynadie, M., Staines, A., Lightfoot, T., Crouch, S., Smith, A., Roman, E., Ryan Diver, W., Offit, K., Zelenetz, A., Klein, R.J., Villano, D.J., Zheng, T., Zhang, Y., Holford, T.R., Turner, J., Southey, M.C., Clavel, J., Virtamo, J., Weinstein, S., Riboli, E., Vineis, P., Kaaks, R., Boeing, H., Tjønneland, A., Angelucci, E., Di Lollo, S., Rais, M., De Vivo, I., Giovannucci, E., Kraft, P., Huang, J., Ma, B., Ye, Y., Chiu, B.C.H., Liang, L., Park, J.-H., Chung, C.C., Weisenburger, D.D., Fraumeni, J.F., Jr and Salles, G., Glenn, M., Cannon-Albright, L., Curtin, K., Wu, X., Smedby, K.E., de Sanjose, S., Skibola, C.F., Berndt, S.I., Birmann, B.M., Chanock, S.J., Rothman, N., LS IRAS EEPI GRA (Gezh.risico-analyse), Sub Atmospheric physics and chemistry, dIRAS RA-I&I RA, dIRAS RA-2, Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Cancer environnement ( EPICENE ), Bordeaux population health ( BPH ), Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Registre des hémopathies malignes de la Gironde, Institut Bergonié - CRLCC Bordeaux, Department of Agronomy, University of Wisconsin-Madison [Madison], Service hématologie Poitiers, CHU, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris Descartes - Paris 5 ( UPD5 ), Oslo and Akershus University College ( OAUC ), Laboratoire de mécanique Biomécanique Polymère Structures ( LaBPS ), Université de Lorraine ( UL ), The Tisch Cancer Institute, Mount Sinai School of Medicine, International Agency for Cancer Research ( IACR ), International Agency for Cancer Research, Registre des hémopathies malignes de Côte d'Or, Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), University of Chicago Medicine, Institut National de la Santé et de la Recherche Médicale ( INSERM ), French National Registry of Childhood Hematological malignancies (NRCH), NRCH, Division of Epidemiology, Public Health and Primary Care, Imperial College London, Unit of Cancer Epidemiology, AOU S. Giovanni Battista, CPO Piemonte, CeRMS, University of Torino, Department of Epidemiology and Public Health, Department Cancer Epidemiology, German Cancer Research Center, Institute of Human Nutrition Potsdam-Rehbruecke, Diet, Cancer and Health, Danish Cancer Society, Justus Liebig University Giessen, Sino French Research Center for Biomedical Imaging ( HIT-INSA ), Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Harbin Institute of Technology ( HIT ), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Chinese Academy of Sciences [Beijing] ( CAS ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer environnement (EPICENE ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, University of Wisconsin-Madison, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Descartes - Paris 5 (UPD5), Akershus University College, Laboratoire de mécanique Biomécanique Polymère Structures (LaBPS), Université de Lorraine (UL), Icahn School of Medicine at Mount Sinai [New York] (MSSM), International Agency for Cancer Research (IACR), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut National de la Santé et de la Recherche Médicale (INSERM), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Justus-Liebig-Universität Gießen (JLU), Sino French Research Center for Biomedical Imaging (HIT-INSA), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Harbin Institute of Technology (HIT), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chinese Academy of Sciences [Beijing] (CAS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Torino = University of Turin (UNITO), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Harbin Institute of Technology (HIT), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Oslo and Akershus University College (OAUC), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
0301 basic medicine, Serum, Male, Lymphoma, analysis, Chronic lymphocytic leukemia, Follicular lymphoma, Global Health, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, immunology, surgery, 0302 clinical medicine, Endocrinology, immune system diseases, single nucleotide polymorphism, Germany, hemic and lymphatic diseases, London, 80 and over, Odds Ratio, genetics, Prospective Studies, B-cell lymphoma, Association Studies Article, Genetics (clinical), Aged, 80 and over, education.field_of_study, telomere, Genome, Leukemia, Age Factors, General Medicine, Environmental exposure, Genomics, Middle Aged, b-cell lymphoma, small cell lymphoma, Italy, 030220 oncology & carcinogenesis, Medicine, epidemiology, Female, France, Risk of B-cell lymphoma subtypes, Risk, Adult, Canada, China, Lymphoma, B-Cell, Genotype, Adolescent, leukocytes, etiology, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Environment, Risk Assessment, methods, Time, 03 medical and health sciences, medicine, Humans, Family, Genetic Predisposition to Disease, education, Molecular Biology, Alleles, Occupational Health, Genetic Association Studies, Aged, B-Cell, International Agencies, Odds ratio, Environmental Exposure, medicine.disease, Telomere, Non-Hodgkin's lymphoma, 030104 developmental biology, Immunology, physiology, Chronic Disease, pathology, Laboratories, metabolism
Abstract

International audience; Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 x 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 x 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk

Published
2016

129. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

Author

Nathaniel Rothman, Yolanda Benavente, Paul Brennan, Qing Lan, Pierluigi Cocco, Simon Crouch, Anneclaire J. De Roos, Josh Wright, Christine F. Skibola, Mark P. Purdue, Elisabete Weiderpass, James R. Cerhan, Randy D. Gascoyne, Maria Grazia Ennas, Kari E. North, Zhaoming Wang, Jinyan Huang, Julie M. Cunningham, Alain Monnereau, Peter Kraft, Patricia Hartge, Edward Giovannucci, Karen Curtin, Giovanna Masala, Jacqueline Clavel, Neil E. Kay, Jacques Riby, María Dolores Chirlaque, John J. Spinelli, Delphine Casabonne, Jenny Turner, Lucia Conde, Lesley F. Tinker, Martha Glenn, Sara S. Strom, Donna K. Arnett, Rebecca Montalvan, Ju-Hyun Park, Melissa C. Southey, Ann Maria, Karin E. Smedby, Lindsay M. Morton, Marc Maynadié, Laurie Burdett, Amy Hutchinson, Bengt Glimelius, W. Ryan Diver, Elio Riboli, Sonja I. Berndt, Lisa A. Cannon-Albright, Kimberly A. Bertrand, Aaron D. Norman, Sara J. Achenbach, Celine M. Vachon, Angela Cox, Xifeng Wu, Theodore R. Holford, Neil E. Caporaso, Joseph F. Fraumeni, Roel Vermeulen, Rudolph Kaaks, Mads Melbye, Joseph Vijai, Kari G. Chaffee, Lauren R. Teras, Rebecca D. Jackson, Lenka Foretova, J. Brice Weinberg, Paige M. Bracci, Sophia S. Wang, Demetrius Albanes, Stephen J. Chanock, Wendy Cozen, Mark Liebow, Anne J. Novak, Hans-Olov Adami, George J. Weiner, Angela Brooks-Wilson, Kenneth Offit, Anne Kricker, Claire M. Vajdic, James McKay, Ellen T. Chang, Baoshan Ma, Cristine Allmer, Susan L. Slager, Brian K. Link, Elizabeth A. Holly, Anthony Staines, Liming Liang, Jarmo Virtamo, Timothy G. Call, Nicola J. Camp, Ruth C. Travis, Alexandra Nieters, Degui Zhi, Brenda M. Birmann, Tait D. Shanafelt, Rachel S. Kelly, Graham G. Giles, Nilanjan Chatterjee, John A. Snowden, Yuanqing Ye, Núria Sala, Tongzhang Zheng, Paolo Boffetta, Lynn R. Goldin, Danylo J. Villano, Jose F. Leis, Paolo Vineis, Lucia Miligi, Jian Gu, Justin M. Leach, Silvia de Sanjosé, Richard K. Severson, Yawei Zhang, Henrik Hjalgrim, Roger L. Milne, Charles E. Lawrence, Meredith Yeager, Moara Machado, Nikolaus Becker, Joseph M. Connors, Anne Zeleniuch-Jacquotte, Giovanni Maria Ferri, Stephanie J. Weinstein, LS IRAS EEPI GRA (Gezh.risico-analyse), Sub Atmospheric physics and chemistry, dIRAS RA-I&I RA, dIRAS RA-2, Berndt, S.I., Camp, N.J., Skibola, C.F., Vijai, J., Wang, Z., Gu, J., Nieters, A., Kelly, R.S., Smedby, K.E., Monnereau, A., Cozen, W., Cox, A., Wang, S.S., Lan, Q., Teras, L.R., Machado, M., Yeager, M., Brooks-Wilson, A.R., Hartge, P., Purdue, M.P., Birmann, B.M., Vajdic, C.M., Cocco, P., Zhang, Y., Giles, G.G., Zeleniuch-Jacquotte, A., Lawrence, C., Montalvan, R., Burdett, L., Hutchinson, A., Ye, Y., Call, T.G., Shanafelt, T.D., Novak, A.J., Kay, N.E., Liebow, M., Cunningham, J.M., Allmer, C., Hjalgrim, H., Adami, H.-O., Melbye, M., Glimelius, B., Chang, E.T., Glenn, M., Curtin, K., Cannon-Albright, L.A., Diver, W.R., Link, B.K., Weiner, G.J., Conde, L., Bracci, P.M., Riby, J., Arnett, D.K., Zhi, D., Leach, J.M., Holly, E.A., Jackson, R.D., Tinker, L.F., Benavente, Y., Sala, N., Casabonne, D., Becker, N., Boffetta, P., Brennan, P., Foretova, L., Maynadie, M., McKay, J., Staines, A., Chaffee, K.G., Achenbach, S.J., Vachon, C.M., Goldin, L.R., Strom, S.S., Leis, J.F., Weinberg, J.B., Caporaso, N.E., Norman, A.D., De Roos, A.J., Morton, L.M., Severson, R.K., Riboli, E., Vineis, P., Kaaks, R., Masala, G., Weiderpass, E., Chirlaque, M.-D., Vermeulen, R.C.H., Travis, R.C., Southey, M.C., Milne, R.L., Albanes, D., Virtamo, J., Weinstein, S., Clavel, J., Zheng, T., Holford, T.R., Villano, D.J., Maria, A., Spinelli, J.J., Gascoyne, R.D., Connors, J.M., Bertrand, K.A., Giovannucci, E., Kraft, P., Kricker, A., Turner, J., Ennas, M.G., Ferri, G.M., Miligi, L., Liang, L., Ma, B., Huang, J., Crouch, S., Park, J.-H., Chatterjee, N., North, K.E., Snowden, J.A., Wright, J., Fraumeni, J.F., Offit, K., Wu, X., De Sanjose, S., Cerhan, J.R., Chanock, S.J., Rothman, N., Slager, S.L., National Cancer Institute ( NIH ), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Registre des hémopathies malignes de Côte d'Or, Mayo Clinic [Rochester], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), and UNICANCER-UNICANCER

Subjects
0301 basic medicine, Medicin och hälsovetenskap, Chronic lymphocytic leukemia, General Physics and Astronomy, Genome-wide association study, VARIANTS, Medical and Health Sciences, Malalties hereditàries, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Chronic, Genetics, RISK, Leukemia, Multidisciplinary, BANK1, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Bcl-2-Like Protein 11, Adaptor Proteins, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Single Nucleotide, Lymphocytic, 3. Good health, PRIORITIZATION, Multidisciplinary Sciences, medicine.anatomical_structure, Science & Technology - Other Topics, TRANSCRIPTION FACTOR EOMESODERMIN, Genetic disorders, EXPRESSION, SUSCEPTIBILITY LOCI, Science, European Continental Ancestry Group, FAS GENE-MUTATIONS, Locus (genetics), Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, CLASSIFICATION, White People, Article, 03 medical and health sciences, Proto-Oncogene Proteins, MD Multidisciplinary, medicine, Genetic predisposition, SNP, Humans, Leucèmia limfocítica crònica, Genetic Predisposition to Disease, Polymorphism, B cell, Serpins, Genetic association, Adaptor Proteins, Signal Transducing, Science & Technology, Signal Transducing, B-Cell, Membrane Proteins, General Chemistry, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 030104 developmental biology, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Apoptosis Regulatory Proteins, T-Box Domain Proteins, FOLLICULAR LYMPHOMA, Genome-Wide Association Study
Abstract

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P, Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near EOMES, SERPINB6 and LPP associated with risk of this disease.

Published
2016

130. Diabetes and the risk of non-Hodgkin's lymphoma and multiple myeloma in the European Prospective Investigation into Cancer and Nutrition

Author

María Dolores Chirlaque, Rudolf Kaaks, Valentina Gallo, Sara Grioni, Nikolaus Becker, Aneire E. Khan, Martine M. Ros, Anne Tjønneland, Amalia Mattiello, Roel Vermeulen, Naomi E. Allen, Åsa Ågren, Petra H.M. Peeters, Vasiliki Benetou, H. Bas Bueno-de-Mesquita, Nerea Larrañaga, Ole Raaschou-Nielsen, Jakob Linseisen, Kim Overvad, Nadia Slimani, Teresa Norat, Eiliv Lund, Eva Ardanaz, Paula Jakszyn, Hans Erik Johnsen, Giovanna Masala, Elio Riboli, Manuela M. Bergmann, Göran Hallmans, Heiner Boeing, Kay-Tee Khaw, Alexandra Nieters, Göran Berglund, Adamina Losada, Sheila Bingham, Antonia Trichopoulou, Jonas Manjer, Sabine Rohrmann, Theodora Psaltopoulou, Paolo Boffetta, Paolo Vineis, Carmen Martinez-Garcia, Rosario Tumino, Pietro Ferrari, Timothy J. Key, Khan, A.E., Gallo, V., Linseisen, J., Kaaks, R., Rohrmann, S., Raaschou-Nielsen, O., Tjønneland, A., Johnsen, H.E., Overvad, K., Bergmann, M.M., Boeing, H., Benetou, V., Psaltopoulou, T., Trichopoulou, A., Masala, G., Mattiello, A., Grioni, S., Tumino, R., Vermeulen, R.C.H., Peeters, P.H.M., Bueno-de-Mesquita, H.B., Ros, M.M., Lund, E., Ardanaz, E., Chirlaque, M.-D., Jakszyn, P., Larrañaga, N., Losada, A., Becker, N., Nieters, A., Martínez-García, C., Ågren, Å., Hallmans, G., Berglund, G., Manjer, J., Allen, N.E., Key, T.J., Bingham, S., Khaw, K.T., Slimani, N., Ferrari, P., Boffetta, P., Norat, T., Vineis, P., and Riboli, E.

Subjects
Adult, Male, Risk, Oncology, medicine.medical_specialty, Diabetes risk non-Hodgkin's lymphoma multiple myeloma European Prospective Investigation Cancer Nutrition, Nutritional Sciences, Comorbidity, Diabetes Complications, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Prospective Studies, ddc:610, Risk factor, Prospective cohort study, Multiple myeloma, Aged, Hematology, business.industry, Lymphoma, Non-Hodgkin, Cancer, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Lymphoma, Non-Hodgkin's lymphoma, Europe, Diabetes Mellitus, Type 2, Immunology, Female, Multiple Myeloma, business, Follow-Up Studies
Abstract

Background: Non-Hodgkin's lymphomas are a heterogeneous group of neoplasms arising from the lymphopoietic system including a wide range of subtypes of either B-cell or T-cell lymphomas. The few established risk factors for the development of these neoplasms include viral infections and immunological abnormalities, but their etiology remains largely unknown. Evidence suggests that certain medical conditions may be linked, through immunosuppression, to the risk of non-Hodgkin's lymphoma. Multiple myeloma is a neoplasm of plasma cells that accounts for approximately 15% of lymphopoietic cancers. Increases in the incidence of non-Hodgkin's lymphoma and multiple myeloma in the past implicate environmental factors as potential causal agents. Design and Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,213 histologically confirmed incident cases of non-Hodgkin's lymphoma and multiple myeloma (594 men; 619 women) were identified during a follow-up of 8.5 years. Cox proportional hazard models were used to explore the association between self-reported diabetes, diagnosed after 30 years of age, and the risk of non-Hodgkin's lymphoma overall and multiple myeloma and various lymphoma subtypes. Results: We found no association between a personal history of diabetes and the risk of non-Hodgkin's lymphoma overall in men (HR: 1.28, 95% CI: 0.89-1.84), in women (HR: 0.71, 95% CI: 0.41-1.24), or in men and women combined (HR: 1.09, 95% CI: 0.80-1.47). Among the B-non-Hodgkin's lymphoma subtypes, we observed a statistically significant increased risk of B-cell chronic lymphocytic leukemia (HR: 2.0, 95% CI: 1.04-3.86) in men, but not in women (HR: 1.07, 95% CI: 0.33-3.43). Conclusions: This prospective study did not provide evidence for a role of self-reported diabetes in the etiology of non-Hodgkin's lymphoma overall or multiple myeloma. We found an increased risk of B-cell chronic lymphocytic leukemia among men with diabetes, but not among women. We hypothesize that diabetes may not play a causal role in the etiology of B-cell chronic lymphocytic leukemia, though the underlying pathogenic mechanisms of both disorders may include shared genetic, host and/or environmental susceptibility factors. ©2008 Ferrata Storti Foundation.

Published
2008

131. Exogenous risk factors for amyotrophic lateral sclerosis

Author

Huisman, M.H.B., Berg, L.H. van den, Veldink, J.H., Vermeulen, R.C.H., and University Utrecht

Subjects
Epidemiology, Dietary intake, Exogenous risk factors, Amyotrophic lateral sclerosis
Abstract

The aims of this thesis were to determine the epidemiology of ALS in the Netherlands, to determine the familial aggregation of ALS with Parkinson disease (PD), dementia, and vascular diseases, and to determine the association between several environmental and lifestyle factors and risk for sporadic ALS. We studied this in a population-based case-control study in the Netherlands, which is called the Prospective ALS study the Netherlands (PAN). The Netherlands provide ideal circumstances for a population-based study, since it is a densely populated country with 16.6 million inhabitants as of January 1, 2010 and an area of 41,528 km2, it has a well-developed infrastructure, and it has easy accessibility of health care to all inhabitants. Our study fulfilled the predefined criteria for a population-based case-control study to yield class I evidence on exogenous risk factors in sporadic ALS; i.e. a large number of newly diagnosed patients using multiple sources of cases ascertainment and with a diagnosis of ALS made applying established criteria, the use of randomly selected population-based and matched controls, high response rates, the use of detailed questionnaires accounting for exposure for disease onset, the quantification of exposures, the blinding of persons gathering the data on diseases status to ensure the uniform effort to gather information equally from affected and unaffected individuals, the blinding of participants and individuals gathering the data as to the hypotheses being tested, and the meticulous attention to avoid recall bias and confounding.

Published
2015

132. Risk factors for amyotrophic lateral sclerosis : Lifestyle, environment and genetics

Author

Seelen, M., Berg, L.H. van den, Veldink, J.H., Es, M.A. van, Vermeulen, R.C.H., and University Utrecht

Subjects
Metabolism, Risk factors, Epidemiology, Genetics, Air pollution, ALS, Environment, Amyotrophic lateral sclerosis, Lifestyle, Head trauma
Abstract

In this thesis the results of studies aiming to identify risk factors for amyotrophic lateral sclerosis (ALS) are described. A population-based case-control design was used to perform (1) epidemiological risk factor studies, examining lifestyle factors and environmental exposures, and (2) genetic studies determining genetic risk variants in ALS. Within these studies novel exposures have been established, which had not been implicated in ALS before, including exposure to traffic related air pollution and diesel motor exhaust. We were able to identify these exposures in two independent populations, in The Netherlands and Ireland, as well as through different study approaches (residential and occupational exposure assessment), presenting convincing evidence for the positive association with ALS risk. These and other ALS associated risk factors described in this thesis (e.g. physical activity, head trauma, high dietary fat intake, low BMI and cholesterol levels, and low alcohol consumption) have provided us with new clues for pathophysiological mechanisms, such as mitochondrial dysfunction, oxidative stress, neuroinflammation and glutamate excitotoxicity. Moreover, we have shown that ALS has a complex etiology in which multiple genetic (and most probably also lifestyle and environmental) factors co-occur to cause ALS. Specifically co-occurring repeat expansions in C9orf72 and NIPA1 were identified. Taking all studies together, we have generated new hypotheses for futurefunctional biologicalstudies to elucidatepathophysiological mechanisms leading to this complex and devastating disease.

Published
2015

133. Quantification and characterization of household air pollution exposure from the use of solid fuels; Clues to the lung cancer epidemic in Xuanwei and Fuyuan, China

Author

Downward, G.S., Brunekreef, B., Vermeulen, R.C.H., and University Utrecht

Subjects
coal, China, lung cancer, technology, industry, and agriculture, household air pollution, respiratory system, solid fuels, complex mixtures, respiratory tract diseases
Abstract

Background: Xuanwei and Fuyuan are two neighbouring counties in Yunnan province China which are remarkable in that they have among the highest lung cancer rates in the nation regardless of gender or smoking status. Previous research has implicated the domestic combustion of locally sourced “smoky” (bituminous) coal as being responsible for the lung cancer epidemic (there are 2 main coal types available, smoky coal, which is common throughout both counties, and “smokeless” coal, which is an anthracite coal available to only limited areas). Previous exposure surveys have suggested that either crystalline quartz and/or polycyclic aromatic hydrocarbons may play a role in carcinogenesis however, this research has been limited in sample size and geographic scope meaning that overall, relatively little is currently understood regarding which component(s) of smoky coal directly contribute to lung cancer risk. The work presented in this thesis represents an extensive exposure assessment survey of residents and households from throughout the Xuanwei and Fuyuan counties. Methods: We enrolled 163 households and their non-smoking female heads from throughout Xuanwei and Fuyuan for study. Samples of fuel, ash, and personal and indoor air measurements were collected. Samples were analysed for multiple pollutants including particulate matter, black carbon, polycyclic aromatic hydrocarbons, and crystalline silica and were compared across different fuel (e.g. smoky coal, smokeless coal, wood) and stove types (e.g. unvented firepits, ventilated stoves). Results: Analysis of coal samples revealed that smoky coal contained higher amounts of volatile matter and quartz than smokeless coal. Analysis of air samples found that the use of smoky coal was associated with higher measurements of particulate matter, particle phase polycyclic aromatic hydrocarbons, and black carbon than smokeless coal but that wood was associated with even higher measurements of particulate matter and black carbon. Minimal quartz was observed in air measurements with ash analysis indicating that the elevated quartz observed in smoky coal largely went on to form part of the ash. Also of note was the finding that air measurements were typically reduced among households using ventilated stoves than households using unvented firepits with the exception of black carbon. Conclusions: The findings presented in this thesis provide valuable insight into potential carcinogenic factors in an area with an exceptionally high lung cancer rate and will be used in an ongoing investigation of lung cancer among non-smoking females in the area. While our findings have generally found that exposure levels are lower among users of ventilated stoves and/or smokeless coal, these levels were still considerably high, indicating that none of the solid fuels in use by this population could truly be considered safe.

Published
2015

134. Lung cancer risk among bricklayers in a pooled analysis of case-control studies

Author

Consonni, Dario, De Matteis, Sara, Pesatori, Angela C, Bertazzi, Pier Alberto, Olsson, Ann C, Kromhout, Hans, Peters, Susan, Vermeulen, Roel Ch, Pesch, Beate, Brüning, Thomas, Kendzia, Benjamin, Behrens, Thomas, Stücker, Isabelle, Guida, Florence, Wichmann, Heinz-Erich, Brüske, Irene, Landi, Maria Teresa, Caporaso, Neil E, Gustavsson, Per, Plato, Nils, Tse, Lap Ah, Yu, Ignatius Tak-Sun, Jöckel, Karl-Heinz, Ahrens, Wolfgang, Pohlabeln, Hermann, Merletti, Franco, Richiardi, Lorenzo, Simonato, Lorenzo, Forastiere, Francesco, Siemiatycki, Jack, Parent, Marie-Élise, Tardón, Adonina, Boffetta, Paolo, Zaridze, David, Chen, Ying, Field, John K, 't Mannetje, Andrea, Pearce, Neil, McLaughlin, John, Demers, Paul, Lissowska, Jolanta, Szeszenia-Dabrowska, Neonila, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Rudnai, Peter, Fabiánová, Eleonóra, Stanescu Dumitru, Rodica, Bueno-de-Mesquita, Bas, Schüz, Joachim, Straif, Kurt, Risk Assessment, Infection & Immunity, dIRAS RA-2, dIRAS RA-I&I RA, LS IRAS EEPI EXAS (Arb.hyg+bl.st.kar.), LS IRAS EEPI GRA (Gezh.risico-analyse), Consonni, D. and De Matteis, S. and Pesatori, A.C. and Bertazzi, P.A. and Olsson, A.C. and Kromhout, H. and Peters, S. and Vermeulen, R.C.H. and Pesch, B. and Brüning, T. and Kendzia, B. and Behrens, T. and Stücker, I. and Guida, F. and Wichmann, H.-E. and Brüske, I. and Landi, M.T. and Caporaso, N.E. and Gustavsson, P. and Plato, N. and Tse, L.A. and Yu, I.T.-S. and Jöckel, K.-H. and Ahrens, W. and Pohlabeln, H. and Merletti, F. and Richiardi, L. and Simonato, L. and Forastiere, F. and Siemiatycki, J. and Parent, M.-É. and Tardón, A. and Boffetta, P. and Zaridze, D. and Chen, Y. and Field, J.K. and Mannetje, A. and Pearce, N. and McLaughlin, J. and Demers, P. and Lissowska, J. and Szeszenia-Dabrowska, N. and Bencko, V. and Foretova, L. and Janout, V. and Rudnai, P. and Fabiánová, E. and Dumitru, R.S. and Bueno-De-Mesquita, H.B. and Schüz, J. and Straif, K., Courcelles, Michel, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano = University of Milan (UNIMI), Imperial College London, 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), The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Institute for Risk Assessment Sciences, Utrecht University [Utrecht], The University of Western Australia (UWA), Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Centre de recherche en épidémiologie et santé des populations (CESP), 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), Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), The Chinese University of Hong Kong [Hong Kong], University Hospital Essen, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, University of Bremen, Unit of Cancer Epidemiology, Université de Turin-CERMS and Centre for Oncologic Prevention, Università degli Studi di Padova = University of Padua (Unipd), Azienda Sanitaria Locale [ROMA] (ASL), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), CIBER de Epidemiología y Salud Pública (CIBERESP), International Prevention Research Institute (IPRI), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Institute of Carcinogenesis, Russian Cancer Research Centre, Keele University [Keele], University of Liverpool, London School of Hygiene and Tropical Medicine (LSHTM), Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), Cancer Care Ontario, The M Sklodowska-Curie Cancer Center and Institute of Oncology, The Nofer Institute of Occupational Medicine, Institute of Hygiene and Epidemiology, Charles University [Prague] (CU)-First Faculty of Medicine, Masaryk University [Brno] (MUNI), Department of Optics [Univ Palacký], Faculty of Science [Univ Palacký], Palacky University Olomouc-Palacky University Olomouc, National Institutes of Environmental Health Sciences, Regional Authority of Public Health [Slovaquia] (RAPH), Ministry of Health of the Slovak Republic [Slovaquia], Institute of Public Health, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Grant sponsor: German Social Accident Insurance (DGUV), Grant number: FP 271, Grant sponsors: Canadian Institutes for Health Researchand Guzzo-SRC Chair in Environm ent and Cancer, National Cancer Institute of Canada, Canadian Cancer Society, Occupational Cancer ResearchCentre, Workplace Safety and Insuranc e Boar d, Canadian Cancer Society, and Cancer Care Ontario, Grant sponsor: European Commission’s INCO Copernicus program, Grant number: IC15-CT96-0313, Grant sponsor: European Union Nuclear Fission Safety Program, Grant number:F14P-CT96-0055, Grant sponsors: French Agency of Health Security (ANSES), Fondation de France, French National Research Agency (ANR),National Institute of Cancer (INCA), Fondation pour la Recherche Medicale, French Institute for Public Health Surveillance (InVS), Health Ministry (DGS), Organization for the Research on Cancer (ARC), and French Ministry of work, solidarity, and public function (DGT), Grant sponsor: Federal Ministry of Education, Science, Research, and Technology, Grant number: 01 HK 173/0), Grant sponsor: Federal Ministry of Science, Grant number:01 HK 546/8, Grant sponsor: Ministry of Labour and Social Affairs, Grant number: IIIb7-27/13, Grant sponsor: Research Grants Council of the Hong Kong Special Administrative Region, China, Grant number: CUHK4460/03M, Grant sponsors: Environmental Epidemiology Program of the Lombardy Region, INAIL, Italian Association for Cancer Research, Region Piedmont, Compagnia di San Paolo, Lazio Region, Health Research Council of New Zealand, New Zealand Department of Labour, Lottery Health Research, Cancer Society of New Zealand, Grant sponsor: Polish State Committee for Scientific Research, Grant number: SPUB-M-COPERNICUS/P-05/DZ-30/99/2000, Grant sponsors: Instituto Universitario de Oncologia, Universidad de Oviedo, Asturias, Fondo de Investigacion Sanitaria (FIS) and Ciber de Epidemiologia y Salud Publica (CIBERESP), Swedish Council for Work Life Research and Swedish Environmental Protection Agency, Dutch Ministry of Health, Welfare and Sports, National Institute of Public Health and the Environment, and Europe Against Cancer Program, Roy Castle Foundation, and Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, Maryland, Risk Assessment, Infection & Immunity, dIRAS RA-2, dIRAS RA-I&I RA, LS IRAS EEPI EXAS (Arb.hyg+bl.st.kar.), LS IRAS EEPI GRA (Gezh.risico-analyse), Università degli Studi di Milano [Milano] (UNIMI), 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), Universita degli Studi di Padova, Charles University and General University Hospital-First Faculty of Medicine, and Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University

Subjects
Male, Epidemiology, control studies, cancer risk, bricklayer, middle aged, occupation, CARCINOGENS, blue collar worker, POPULATION, comparative study, education.field_of_study, MESH: Middle Aged, risk assessment, WORKERS, MEN, MESH: Carcinoma, Squamous Cell, clinical trial, MESH: Follow-Up Studies, Prognosis, MESH: Case-Control Studies, 3. Good health, Occupational Diseases, [SDV] Life Sciences [q-bio], OCCUPATIONAL-EXPOSURE, hospital based case control study, Oncology, priority journal, risk factor, Adenocarcinoma, Carcinoma, Squamous Cell, case, Human, MESH: Occupational Diseases, medicine.medical_specialty, national cancer institute of, additional supporting information may, case–control studies, employment statu, MESH: Prognosis, Article, Follow-Up Studie, MESH: International Agencies, [SDV.CAN] Life Sciences [q-bio]/Cancer, carcinogen, adult, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, research and guzzo-src chair, education, CRYSTALLINE SILICA DUST, fp 271, Science & Technology, MESH: Humans, Occupational health, MORTALITY, health care facility, Construction Industry, Case-control study, bricklayers, Odds ratio, case control study, medicine.disease, dguv, lung adenocarcinoma, major clinical study, Lung neoplasm, occupational hazard, MESH: Lung Neoplasms, Occupational Disease, occupational cancer, multicenter study, age, Relative risk, small cell lung cancer, Occupational medicine, MESH: Female, population research, Cancer Research, online version of this, [SDV]Life Sciences [q-bio], canada, Medizin, medicine.disease_cause, MESH: Occupational Exposure, grant number, Risk Factors, MESH: Risk Factors, Carcinoma, Small Cell, Medicine (all), international cooperation, grant sponsor, article, canadian institutes for health, MESH: Carcinoma, Small Cell, be found in the, MESH: Construction Industry, female, NORDIC COUNTRIES, International Agencie, canadian cancer society, epidemiology, grant sponsors, Gustavsson, in environment and cancer, Case-Control Studie, Life Sciences & Biomedicine, lifespan, prognosi, Population, UNITED-STATES, [SDV.CAN]Life Sciences [q-bio]/Cancer, lung neoplasms, Asbestos, smoking, building industry, occupational health, Internal medicine, Occupational Exposure, medicine, follow up, controlled study, occupational, Lung cancer, population based case control study, Plato, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, adenocarcinoma, business.industry, case-control studies, Risk Factor, Carcinoma, MESH: Adenocarcinoma, International Agencies, Small Cell, Confidence interval, MESH: Male, human tissue, Surgery, lung cancer, german social accident insurance, Squamous Cell, Bricklayers, Case-control studies, Lung neoplasms, Adenocarcinoma, Case-Control Studies, Female, Follow-Up Studies, Lung Neoplasms, Middle Aged, business, CONSTRUCTION-INDUSTRY, squamous cell lung carcinoma
Abstract

Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case–control studies on lung cancer and the joint effects of occupational carcinogens. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28–1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32–1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93–1.64, 155/120 cases/controls) in hospital-based studies. There was a clear positive trend with length of employment (p < 0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42–1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44–2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95–1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos. WHAT'S NEW?: In their work, bricklayers can be exposed to various airborne carcinogens, including crystalline silica and asbestos. Previous studies of cancer risk have not accounted for full employment history or smoking status, and failed to establish a firm relationship between bricklaying and lung cancer. In this study, the authors used data from the largest collection of case-control studies on lung cancer with complete occupational and smoking history existing today, the SYNERGY project. They found clear evidence that lung cancer risk increases in proportion to the length of time spent working as a bricklayer, paving the way for better protection and compensation for those in this occupation.

Published
2015

135. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

Author

Lenka Foretova, Sophia S. Wang, Hans-Olov Adami, Demetrius Albanes, Andrew D. Zelenetz, Emanuele Angelucci, Paige M. Bracci, Hervé Tilly, Hervé Ghesquières, John J. Spinelli, Kimberly A. Bertrand, Francine Laden, Rebecca D. Jackson, Wendy Cozen, Anne J. Novak, Charles C. Chung, Meredith Yeager, Brian C.-H. Chiu, Jenny Turner, Melissa C. Southey, Gianluca Severi, Simonetta Di Lollo, Lindsay M. Morton, Mark Liebow, Theodore R. Holford, Paolo Boffetta, Paul I.W. de Bakker, Joseph Vijai, Claire M. Vajdic, Anne Kricker, Mark P. Purdue, Stephanie J. Weinstein, Ahmet Dogan, Alain Monnereau, Patricia Hartge, Degui Zhi, Amy K. Hutchinson, Brenda M. Birmann, Charles Lawrence, Elizabeth A. Holly, Marco Rais, Anneclaire J. De Roos, Karin E. Smedby, Sonja I. Berndt, Stephen J. Chanock, Lucia Conde, Stephen M. Ansell, Yan W. Asmann, Yuanqing Ye, David G. Cox, Elio Riboli, Joseph F. Fraumeni, Christine F. Skibola, Christopher R. Flowers, Angela Brooks-Wilson, Amelie S. Veron, Jarmo Virtamo, Danylo J. Villano, Thierry Jo Molina, W. Ryan Diver, James D. McKay, Kenneth Offit, Eve Roman, Jinyan Huang, Xifeng Wu, Marc Maynadie, Yolanda Benavente, Baoshan Ma, Brian K. Link, Thomas E. Witzig, Mads Melbye, George J. Weiner, Zhaoming Wang, Corinne Haioun, Alex Smith, Anthony Staines, Anne Zeleniuch-Jacquotte, Martyn T. Smith, Paul Brennan, Nilanjan Chatterjee, Tracy Lightfoot, Eleanor Kane, Bengt Glimelius, Ju-Hyun Park, Robert J. Klein, Alexandra Nieters, Heiner Boeing, Mariagrazia Zucca, Nathaniel Rothman, Jacqueline Clavel, Qing Lan, Susan L. Slager, Rudolph Kaaks, Diana Zelenika, Nikolaus Becker, Henrik Hjalgrim, Rachel S. Kelly, Roel Vermeulen, Graham G. Giles, Anne Tjønneland, Carrie A. Thompson, Laurie Burdett, Richard K. Severson, Dimitrios Trichopoulos, Yawei Zhang, Kari E. North, Tongzhang Zheng, Jian Gu, Edward Giovannucci, Jacques Riby, Simon Crouch, Gilles Salles, Silvia de Sanjosé, Dennis D. Weisenburger, Thomas M. Habermann, Paolo Vineis, Lesley F. Tinker, Joshua N. Sampson, Liming Liang, Peter Kraft, James R. Cerhan, Lauren R. Teras, Cerhan, J.R., Berndt, S.I., Vijai, J., Ghesquières, H., McKay, J., Wang, S.S., Wang, Z., Yeager, M., Conde, L., De Bakker, P.I.W., Nieters, A., Cox, D., Burdett, L., Monnereau, A., Flowers, C.R., De Roos, A.J., Brooks-Wilson, A.R., Lan, Q., Severi, G., Melbye, M., Gu, J., Jackson, R.D., Kane, E., Teras, L.R., Purdue, M.P., Vajdic, C.M., Spinelli, J.J., Giles, G.G., Albanes, D., Kelly, R.S., Zucca, M., Bertrand, K.A., Zeleniuch-Jacquotte, A., Lawrence, C., Hutchinson, A., Zhi, D., Habermann, T.M., Link, B.K., Novak, A.J., Dogan, A., Asmann, Y.W., Liebow, M., Thompson, C.A., Ansell, S.M., Witzig, T.E., Weiner, G.J., Veron, A.S., Zelenika, D., Tilly, H., Haioun, C., Molina, T.J., Hjalgrim, H., Glimelius, B., Adami, H.-O., Bracci, P.M., Riby, J., Smith, M.T., Holly, E.A., Cozen, W., Hartge, P., Morton, L.M., Severson, R.K., Tinker, L.F., North, K.E., Becker, N., Benavente, Y., Boffetta, P., Brennan, P., Foretova, L., Maynadie, M., Staines, A., Lightfoot, T., Crouch, S., Smith, A., Roman, E., Diver, W.R., Offit, K., Zelenetz, A., Klein, R.J., Villano, D.J., Zheng, T., Zhang, Y., Holford, T.R., Kricker, A., Turner, J., Southey, M.C., Clavel, J., Virtamo, J., Weinstein, S., Riboli, E., Vineis, P., Kaaks, R., Trichopoulos, D., Vermeulen, R.C.H., Boeing, H., Tjonneland, A., Angelucci, E., Di Lollo, S., Rais, M., Birmann, B.M., Laden, F., Giovannucci, E., Kraft, P., Huang, J., Ma, B., Ye, Y., Chiu, B.C.H., Sampson, J., Liang, L., Park, J.-H., Chung, C.C., Weisenburger, D.D., Chatterjee, N., Fraumeni, J.F., Slager, S.L., Wu, X., De Sanjose, S., Smedby, K.E., Salles, G., Skibola, C.F., Rothman, N., and Chanock, S.J.

Subjects
Limfomes, Genotype, Chronic lymphocytic leukemia, Cèl·lules B, Quantitative Trait Loci, Population, Follicular lymphoma, Genome-wide association study, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, White People, Genetics, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, education, Genetic association, Likelihood Functions, education.field_of_study, B cells, Chromosome Mapping, Computational Biology, medicine.disease, Genetic Loci, large B cell lymphoma (DLBCL), Lymphomas, Lymphoma, Large B-Cell, Diffuse, Diffuse large B-cell lymphoma, Genome-Wide Association Study
Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10 '21), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10 '10), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10 '8) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10 '13 and 3.63 × 10 '11, respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL. © 2014 Nature America, Inc. All rights reserved.

Published
2014

136. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Author

Roel Vermeulen, Robert J. Klein, Lindsay M. Morton, Lauren R. Teras, John A. Snowden, Angela Brooks-Wilson, Sonja I. Berndt, Pierluigi Cocco, Wendy Cozen, Rebecca D. Jackson, Lenka Foretova, Henrik Hjalgrim, Bruce K. Armstrong, Neil E. Caporaso, Mark P. Purdue, Itziar Salaverria, Anne J. Novak, Elizabeth A. Holly, Anneclaire J. De Roos, Kenneth Offit, Liming Liang, Paolo Vineis, Stephen J. Chanock, Anne Kricker, Sophia S. Wang, Vicki A. Morrison, George J. Weiner, Lesley F. Tinker, Nilanjan Chatterjee, Hans-Olov Adami, Ellen T. Chang, Mark Liebow, Mark C. Lanasa, Lisa A. Cannon-Albright, Andrew D. Zelenetz, Claire M. Vajdic, Sara J. Achenbach, James McKay, Gianluca Severi, Kari E. North, Edward Giovannucci, Rudolf Kaaks, Angela Cox, Karin E. Smedby, Susan L. Slager, Aaron D. Norman, Brian K. Link, Charles E. Lawrence, Amy Hutchinson, Jarmo Virtamo, Kari G. Rabe, Theodore R. Holford, Joshua N. Sampson, Lucia Conde, Timothy G. Call, Alice H. Wang, Julie M. Cunningham, Demetrius Albanes, Nikolaus Becker, Elio Riboli, Alain Monnereau, Francine Laden, Celine M. Vachon, Charles C. Chung, Ruth C. Travis, Brandt Jones, Brenda M. Birmann, Nathaniel Rothman, Yolanda Benavente, Kevin B. Jacobs, Tait D. Shanafelt, Rachel S. Kelly, Anthony Staines, Marc Maynadié, Lucia Miligi, Paul Brennan, Silvia de Sanjosé, Karen Curtin, Tongzhang Zheng, Sílvia Beà, Bengt Glimelius, Elias Campo, W. Ryan Diver, Jeffrey Yuenger, Qing Lan, Peter Kraft, Kimberly A. Bertrand, Laurie Burdette, Martha Glenn, Jenny Turner, J. Brice Weinberg, Ju-Hyun Park, Paolo Boffetta, Jacqueline Clavel, Joseph F. Fraumeni, Martyn T. Smith, Logan G. Spector, Lynn R. Goldin, Mads Melbye, Paige M. Bracci, David Martín-García, Sara S. Strom, Christine F. Skibola, Vijai Joseph, Nicola J. Camp, Dimitrios Trichopoulos, Richard K. Severson, Elisabete Weiderpass, James R. Cerhan, Maria Grazia Ennas, Carlos López-Otín, Yawei Zhang, Jose F. Leis, Angel Carracedo, Graham G. Giles, Patricia Hartge, María Dolores Chirlaque, Zhaoming Wang, Martha S. Linet, John J. Spinelli, Alexandra Nieters, Anne Zeleniuch-Jacquotte, Giovanni Maria Ferri, Stephanie J. Weinstein, Meredith Yeager, Giovanna Masala, Neil E. Kay, Jacques Riby, Simon Crouch, Josh Wright, Berndt, S.I., Skibola, C.F., Joseph, V., Camp, N.J., Nieters, A., Wang, Z., Cozen, W., Monnereau, A., Wang, S.S., Kelly, R.S., Lan, Q., Teras, L.R., Chatterjee, N., Chung, C.C., Yeager, M., Brooks-Wilson, A.R., Hartge, P., Purdue, M.P., Birmann, B.M., Armstrong, B.K., Cocco, P., Zhang, Y., Severi, G., Zeleniuch-Jacquotte, A., Lawrence, C., Burdette, L., Yuenger, J., Hutchinson, A., Jacobs, K.B., Call, T.G., Shanafelt, T.D., Novak, A.J., Kay, N.E., Liebow, M., Wang, A.H., Smedby, K.E., Adami, H.-O., Melbye, M., Glimelius, B., Chang, E.T., Glenn, M., Curtin, K., Cannon-Albright, L.A., Jones, B., Diver, W.R., Link, B.K., Weiner, G.J., Conde, L., Bracci, P.M., Riby, J., Holly, E.A., Smith, M.T., Jackson, R.D., Tinker, L.F., Benavente, Y., Becker, N., Boffetta, P., Brennan, P., Foretova, L., Maynadie, M., McKay, J., Staines, A., Rabe, K.G., Achenbach, S.J., Vachon, C.M., Goldin, L.R., Strom, S.S., Lanasa, M.C., Spector, L.G., Leis, J.F., Cunningham, J.M., Weinberg, J.B., Morrison, V.A., Caporaso, N.E., Norman, A.D., Linet, M.S., De Roos, A.J., Morton, L.M., Severson, R.K., Riboli, E., Vineis, P., Kaaks, R., Trichopoulos, D., Masala, G., Weiderpass, E., Chirlaque, M.-D., Vermeulen, R.C.H., Travis, R.C., Giles, G.G., Albanes, D., Virtamo, J., Weinstein, S., Clavel, J., Zheng, T., Holford, T.R., Offit, K., Zelenetz, A., Klein, R.J., Spinelli, J.J., Bertrand, K.A., Laden, F., Giovannucci, E., Kraft, P., Kricker, A., Turner, J., Vajdic, C.M., Ennas, M.G., Ferri, G.M., Miligi, L., Liang, L., Sampson, J., Crouch, S., Park, J.-H., North, K.E., Cox, A., Snowden, J.A., Wright, J., Carracedo, A., Lopez-Otin, C., Bea, S., Salaverria, I., Martin-Garcia, D., Campo, E., Fraumeni Jr., J.F., De Sanjose, S., Hjalgrim, H., Cerhan, J.R., Chanock, S.J., Rothman, N., and Slager, S.L.

Subjects
Risk, Linkage disequilibrium, Chronic lymphocytic leukemia, Single-nucleotide polymorphism, Locus (genetics), Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Article, Genetics, medicine, Humans, Genetic Predisposition to Disease, Leucèmia limfocítica crònica, Genome-wide association studies (GWAS), B-cell lymphoma, chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL), Genetic association, Recombination, Genetic, Genomics, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Genòmica, Leukemia, Genetic Loci, Case-Control Studies, Chromosomes, Human, Pair 2, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10-8), 18q21.32 (PMAIP1, P = 2.51 × 10 -8), 15q15.1 (BMF, P = 2.71 × 10-10) and 2p22.2 (QPCT, P = 1.68 × 10-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10-8) and 5p15.33 (TERT, P = 1.92 × 10-7). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism. © 2013 Nature America, Inc. All rights reserved.

Published
2013

137. Malignant mesothelioma and asbestos-related lung cancer: diagnosis, prognosis and burden

Author

van der Bij, S., Moons, K. (Carl) G.M., de Mol, B.A.J.M., Koffijberg, Erik, Vermeulen, R.C.H., and University Utrecht

Subjects
respiratory system, respiratory tract diseases
Abstract

The negative health-related consequences of the use of asbestos have become very clear and widely recognized. This thesis focused on the most frequent asbestos induced cancers: mesothelioma and lung cancer. Mesothelioma A confirmed diagnosis of malignant mesothelioma is important to ensure proper medical care but is also required for patients to initiate a claim for financial compensation. We found that some patients may not obtain compensation when still alive as mesothelioma presence could not be confirmed pathologically, which is the gold standard for mesothelioma. If pathologic material is not sufficient, however, a consensus diagnosis by an expert panel using all available patient information is a valid alternative. To speed up the diagnostic process numerous so-called non-invasive biomarker tests have been developed to facilitate the diagnostic work-up of malignant mesothelioma. To investigate the diagnostic performance of these markers for the detection of malignant mesothelioma a structured review was conducted. We showed that the most frequently studied immunohistochemical markers for cytological analysis were EMA, Ber-Ep4, CEA, and calretinin. The most frequently investigated serum marker was SMRP. However, none of these markers was able to discriminate between malignant mesothelioma and other (lung) diseases. As more treatment options have become available for patients with malignant mesothelioma it is valuable to regularly update survival estimates in patients with malignant mesothelioma. Using a large group of patients with a confirmed diagnosis of malignant mesothelioma we found that only 47% of the patients were still alive one year after diagnosis, 20% after two years and 15% after three years. Prognostic variables independently associated with worse survival were: older age, a specific subtype of the cancer, and a non-pleural localization of the cancer. Asbestos-related lung cancer Exposure to asbestos is known to increase the risk of lung cancer but the exact relationship between exposure and risk is unknown. Particularly at relatively low exposure levels, it is important to estimate the excess risk due to asbestos, as these exposure levels are most frequently seen in The Netherlands. We provided new evidence that at lower asbestos exposure levels the increase in relative risk of lung cancer due to asbestos exposure may be larger than was expected and calculated from previous studies. Finally, we estimated the expected total number of lung cancers due to asbestos exposure in the coming twenty years in the Netherlands using three different, plausible modeling methods. Assumptions and evidence used as input varied widely between these methods. We found that the three modeling methods yield an estimated number of asbestos related lung cancer in the next two decades varying from 6,500 to 22,000 cases. Until more accurate evidence becomes available, the exact impact of asbestos exposure on the lung cancer burden will remain uncertain, but likely between these estimated numbers.

Published
2012

138. Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC)

Author

Beatrice Malmer, Jonas Manjer, Anne Tjønneland, Paolo Vineis, Laudina Rodríguez Suárez, Carlos A. González, Roel Vermeulen, Rosario Tumino, H. Bas Bueno-de-Mesquita, Amalia Mattiello, Paolo Crosignani, Kim Overvad, Aurelio Barricarte, Franco Berrino, Pietro Ferrari, Jakob Linseisen, Ole Raaschou-Nielsen, Elio Riboli, Sheila Bingham, Göran Berglund, Timothy J. Key, Giovanna Masala, Antonia Trichopoulou, Manuela M. Bergmann, Stefano Rosso, Sophia Zackrisson, Heiner Boeing, Kay-Tee Khaw, Göran Hallmans, Nadia Slimani, David Neasham, Kaspar René Nielsen, Ruth C. Travis, Paolo Boffetta, Ahlem Sifi, Carmen Navarro, Rudolf Kaaks, Eiliv Lund, Neasham, D., Sifi, A., Nielsen, K.R., Overvad, K., Raaschou-Nielsen, O., Tjønneland, A., Barricarte, A., González, C.A., Navarro, C., Suarez, L.R., Travis, R.C., Key, T., Linseisen, J., Kaaks, R., Crosignani, P., Berrino, F., Rosso, S., Mattiello, A., Vermeulen, R.C.H., Bueno-de-Mesquita, H.B., Berglund, G., Manjer, J., Zackrisson, S., Hallmans, G., Malmer, B., Bingham, S., Khaw, K.T., Bergmann, M.M., Boeing, H., Trichopoulou, A., Masala, G., Tumino, R., Lund, E., Slimani, N., Ferrari, P., Boffetta, P., Vineis, P., and Riboli, E.

Subjects
Adult, Male, medicine.medical_specialty, Lymphoma, 03 medical and health sciences, 0302 clinical medicine, Age Distribution, immune system diseases, Internal medicine, hemic and lymphatic diseases, Occupational Exposure, Epidemiology, medicine, Humans, multicentre prospective cohort study, ddc:610, Risk factor, Occupations, Prospective cohort study, Multiple myeloma, 030304 developmental biology, risk, Aged, 0303 health sciences, Occupation, business.industry, Lymphoma, Non-Hodgkin, Public Health, Environmental and Occupational Health, Middle Aged, medicine.disease, 3. Good health, Surgery, European Prospective Investigation into Cancer and Nutrition, Europe, Occupational Diseases, 030220 oncology & carcinogenesis, Plasmacytoma, Female, business, EPIC, Epidemiologic Methods, Cohort study
Abstract

ObjectivesEvidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study.MethodsWe investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348 555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma.ResultsThe following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6).ConclusionThe findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.

Published
2010

139. Use of proteomics for the early diagnosis fo breast cancer

Author

van Winden, A.W.J., Beijnen, J.H., Peeters, Petra H.M., van Gils, Carla H., Vermeulen, R.C.H., and University Utrecht

Abstract

Breast cancer mortality rates in The Netherlands are among the highest in Europe. To improve breast cancer survival, early detection is of vital importance. The introduction of the national breast cancer screening program has led to an improvement in stage distribution at diagnosis of breast cancer. But, for women for whom mammography is less effective, e.g. because of high density of the breast tissue, early detection techniques other than mammography would be very helpful. In the studies described in this thesis we searched for blood-based proteins that could indicate the presence of a breast tumor in an early stage. To this end, we first compared protein profiles in serum samples of symptomatic primary breast cancer patients and healthy women. We detected several proteins that showed statistically significantly higher or lower concentrations in breast cancer patients compared to healthy controls. In a study investigating pre-diagnostic serum samples, we found that two of these proteins, a 4.3 kDa fragment of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) and C3a des-arginine anaphylatoxin (C3adesArg) (8.9 kDa), were already increased in serum samples that were collected up to three years before the diagnosis of breast cancer. In a subsequent study we investigated the discriminative value of several peptides that were supposed to be generated by cancer specific exoproteases. Two of these peptides, amongst which a 2.4 kDa fragment of ITIH4, were found to be statistically significantly higher in breast cancer patients. After surgical removal of the tumor, concentrations of both peptides decreased to levels comparable to those in healthy controls. Asymptomatic breast lesions that are currently undetectable by mammographic screening may be detectable in the future using these potential breast cancer markers. Further studies are needed to confirm these results and to exclude false positive findings. The methods described in this thesis may also contribute to the detection of markers for monitoring progression of disease and response to therapy.

Published
2010

140. Consumption of meat and dairy and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition

Author

Kay-Tee Khaw, Petra H.M. Peeters, Aurelio Barricarte, Esther Molina, Nikolaus Becker, Androniki Naska, Miren Dorronsoro, Vassiliki Benetou, Jonas Manjer, Nadia Slimani, Valeria Pala, Guri Skeie, Ulrika Ericson, Ruth C. Travis, Magritt Brustad, Kim Overvad, Rosario Tumino, Nicholas J. Wareham, Ole Raaschou-Nielsen, Beatrice Melin, Jakob Linseisen, Aneire E. Khan, Paolo Vineis, Giovanna Masala, Paolo Boffetta, Eiliv Lund, H. Bas Bueno-de-Mesquita, Antonia Trichopoulou, Teresa Norat, Heiner Boeing, Anne-Claire Vergnaud, Roel Vermeulen, Sabina Rinaldi, Rudolf Kaaks, Paula Jakszyn, Amalia Mattiello, Marianne Uhre Jakobsen, Marie-Christine Boutron-Ruault, Anne Tjønneland, María José Tormo, Timothy J. Key, Manuela M. Bergmann, Sabine Rohrmann, Marcial Argüelles, University of Zurich, Rohrmann, S, Rohrmann, S., Linseisen, J., Jakobsen, M.U., Overvad, K., Raaschou-Nielsen, O., Tjonneland, A., Boutron-Ruault, M.C., Kaaks, R., Becker, N., Bergmann, M., Boeing, H., Khaw, K.-T., Wareham, N.J., Key, T.J., Travis, R., Benetou, V., Naska, A., Trichopoulou, A., Pala, V., Tumino, R., Masala, G., Mattiello, A., Brustad, M., Lund, E., Skeie, G., Bueno-De-Mesquita, H.B., Peeters, P.H.M., Vermeulen, R.C.H., Jakszyn, P., Dorronsoro, M., Barricarte, A., Tormo, M.-J., Molina, E., Argüelles, M., Melin, B., Ericson, U., Manjer, J., Rinaldi, S., Slimani, N., Boffetta, P., Vergnaud, A.-C., Khan, A., Norat, T., and Vineis, P.

Subjects
Male, Oncology, medicine.medical_specialty, Cancer Research, Lymphoma, B-Cell, Consumption, lymphoma, 610 Medicine & health, Lymphoma, T-Cell, Risk Assessment, Cohort Studies, Food group, meat, Cheese, immune system diseases, Internal medicine, hemic and lymphatic diseases, lymhomas, meat consumption, dairy consumption, cohort study, Humans, Medicine, 1306 Cancer Research, ddc:610, Risk factor, risk, business.industry, Lymphoma, Non-Hodgkin, Cancer, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), European Prospective Investigation into Cancer and Nutrition, Yogurt, medicine.disease, Lymphoma, Europe, Relative risk, Immunology, dairy, Female, 2730 Oncology, Dairy Products, Waldenstrom Macroglobulinemia, business, Risk assessment, Cohort study
Abstract

The consumption of meat and other foods of animal origin is a risk factor for several types of cancer, but the results for lymphomas are inconclusive. Therefore, we examined these associations among 411,097 participants of the European Prospective Investigation into Cancer and Nutrition. During a median follow-up of 8.5 years, 1,334 lymphomas (1,267 non-Hodgkin lymphoma (NHL) and 67 Hodgkin lymphomas) were identified. Consumption of red and processed meat, poultry, milk and dairy products was assessed by dietary questionnaires. Cox proportional hazard regression was used to evaluate the association of the consumption of these food groups with lymphoma risk. Overall, the consumption of foods of animal origin was not associated with an increased risk of NHLS or HL, but the associations with specific subgroups of NHL entities were noted. A high intake of processed meat was associated with an increased risk of B-cell chronic lymphocytic leukemia (BCLL) [relative risk (RR) per 50 g intake = 1.31, 95% confidence interval (CI) 1.06-1.63], but a decreased risk of follicular lymphomas (FL) (RR = 0.58; CI 0.38-0.89). A high intake of poultry was related to an increased risk of B-cell lymphomas (RR = 1.22; CI 1.05-1.42 per 10 g intake), FL (RR = 1.65; CI 1.18-2.32) and BCLL (RR = 1.54; CI 1.18-2.01) in the continuous models. In conclusion, no consistent associations between red and processed meat consumption and lymphoma risk were observed, but we found that the consumption of poultry was related to an increased risk of B-cell lymphomas. Chance is a plausible explanation of the observed associations, which need to be confirmed in further studies. Copyright © 2010 UICC.

Published
2010

141. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

Author

Yeul Hong Kim, Sonja I. Berndt, José María Huerta, Morgan Rouprêt, Reury Perng Perng, Yi Young Choi, Lindsay M. Morton, Roberto Tirabosco, H. Bas Bueno-de-Mesquita, Wendy Cozen, Neil E. Caporaso, Stephen J. Chanock, Zhenhong Zhao, Dina Halai, Neyssa Marina, Ann L. Oberg, Stephen M. Ansell, Zhibin Hu, Donghui Li, Anne J. Novak, Jenny Turner, Wen Tan, Julie E. Buring, Stefano Porru, Qincheng He, Tania Carreón, Guoping Wu, Graham G. Giles, Claire M. Vajdic, Rudolf Kaaks, Ulrika Andersson, Susan L. Slager, Jen Yu Hung, Luis Sierrasesúmaga, Roel Vermeulen, Louise A. Brinton, Myron D. Gross, Jennifer Prescott, E. Lund, Chih Yi Chen, Jin Eun Choi, Chaoyu Wang, George J. Weiner, H. Dean Hosgood, Haixin Li, Carrie A. Thompson, Núria Malats, James McKay, Stephanie J. Weinstein, Young Tae Kim, Emily White, Pan-Chyr Yang, Orestis A. Panagiotou, Robert J. Klein, Joseph Vijai, Josep Lloreta, Immaculata De Vivo, Sofia Pavanello, Thomas E. Witzig, Montserrat Garcia-Closas, Roger Henriksson, Bryan A. Bassig, Tait D. Shanafelt, Rachel S. Kelly, Joseph M. Connors, Marco Rais, Wu Chou Su, Alex Smith, John J. Spinelli, Julie M. Gastier-Foster, Anne Kricker, In Kyu Park, Marc J. Gunter, Chancellor Hohensee, Simon Crouch, Jarmo Virtamo, M. G. Ennas, Lucia Conde, Lotte Maxild Mortensen, Lenka Foretova, Eric J. Duell, Anthony Staines, Hongyan Chen, Baosen Zhou, Brian M. Wolpin, Simone Benhamou, Zhaoming Wang, Françoise Clavel-Chapelon, Charles C. Chung, Nan Hu, Domenico Palli, Rebecca Montalvan, Thomas M. Habermann, Debra T. Silverman, Preetha Rajaraman, Christian C. Abnet, Wei-Yen Lim, Yuh Min Chen, Michelle Cotterchio, Lucia Miligi, Claudia Maria Hattinger, Eve Roman, Christopher Kim, Federico Canzian, Alan D. L. Sihoe, Sharon A. Savage, Mark P. Purdue, Maria Teresa Landi, Susan M. Gapstur, M Zucca, Yuanqing Ye, Jian Su, Chong-Jen Yu, Edward Giovannucci, Alain Monnereau, Afshan Siddiq, Ralph L. Erickson, Katherine A. McGlynn, Petra H.M. Peeters, W. Ryan Diver, David Van Den Berg, Gloria M. Petersen, Judith Hoffman-Bolton, Xiao-Ou Shu, Ying Chen, Eric J. Jacobs, Heiner Boeing, Sophia S. Wang, Hans-Olov Adami, Yuqing Li, Jacqueline Clavel, Ellen T. Chang, Tongzhang Zheng, William Pao, Hideo Kunitoh, Ulrike Peters, Jenny Chang-Claude, Alexandra Nieters, Silvia de Sanjosé, Chen Wu, Anders Ahlbom, Jun Suk Kim, Fredrick R. Schumacher, Roberta McKean-Cowdin, Laurence N. Kolonel, Herbert Yu, Li Liu, Vittorio Krogh, Tangchun Wu, Ho Il Yoon, Joseph F. Fraumeni, Olivier Cussenot, Jae Sook Sung, Kari E. North, Andrew D. Zelenetz, Ana Patiño-García, Anne Zeleniuch-Jacquotte, Christopher A. Haiman, Biyun Qian, Giovanni Maria Ferri, Rebecca Rodabough, Xifeng Wu, Maria Feychting, Kuan-Yu Chen, Laure Dossus, Jianjun Liu, Jean Wactawski-Wende, Constance Chen, Robert L. Grubb, Paolo Vineis, Mads Melbye, Chien Chung Lin, Malin Sund, Wei Zheng, Jun Xu, Yi Song Chen, Kay-Tee Khaw, Richard K. Severson, Kun-Chieh Chen, Jian-Min Yuan, Bu Tian Ji, Simonetta Di Lollo, Ping Xu, Howard D. Sesso, Yoo Jin Jung, Margaret R. Karagas, Piero Picci, Gianluca Severi, Margaret A. Tucker, Ti Ding, Gee-Chen Chang, Li Hsin Chien, She-Juan An, Maria Pik Wong, Chien-Jen Chen, Jonine D. Figueroa, Sun-Seog Kweon, Katia Scotlandi, Sara H. Olson, Kendra Schwartz, Chang Hyun Kang, Marta Crous-Bou, Yawei Zhang, Ludmila Prokunina-Olsson, Yolanda Benavente, Christine D. Berg, Kala Visvanathan, Loic Le Marchand, Takashi Kohno, Nilanjan Chatterjee, Tracy Lightfoot, Zhihua Yin, Lee E. Moore, Joanne S. Colt, Laurie Burdett, Tetsuya Mitsudomi, Harvey A. Risch, Alfredo Carrato, Hyo Sung Jeon, Victoria L. Stevens, Richard Gorlick, Danylo J. Villano, Alison P. Klein, Angela Brooks-Wilson, Joshua N. Sampson, Chu Chen, You-Lin Qiao, Kouya Shiraishi, Alan R. Schned, Dominique S. Michaud, Peng Guan, Philip R. Taylor, Gerald L. Andriole, John K.C. Chan, Eva Comperat, Randy D. Gascoyne, Marc Maynadie, Kyong Hwa Park, Amanda Black, Charles Kooperberg, Andrea La Croix, Kenneth Offit, Peter Kraft, David Thomas, Manuela Gago-Dominguez, Manolis Kogevinas, Theodore R. Holford, Pamela L. Horn-Ross, Xingzhou He, Massimo Serra, Satu Männistö, Christoffer Johansen, Meredith Yeager, Robert N. Hoover, Mary Ann Butler, William Wheeler, Jian Gu, Wei Wu, Ying Hsiang Chen, Leslie Bernstein, Yao Jen Li, David J. Hunter, In-Jae Oh, Jay S. Wunder, Meng Zhu, Henrik Hjalgrim, Martyn T. Smith, Alisa M. Goldstein, Linda M. Liao, Chao Agnes Hsiung, Ruth C. Travis, Jiucun Wang, Marie-Christine Boutron-Ruault, Daru Lu, Reina García-Closas, Avima M. Ruder, Martha S. Linet, Wei Tang, Geraldine Cancel-Tassin, Brian K. Link, Rebecca D. Jackson, J. Michael Gaziano, Malcolm C. Pike, Yu-Tang Gao, Lisa Mirabello, Alan A. Arslan, Hong Zheng, Nicolas Wentzensen, Chung Hsing Chen, I. Shou Chang, Meir J. Stampfer, Brenda M. Birmann, Alison Johnson, Wong-Ho Chow, Chin-Fu Hsiao, Neal D. Freedman, Robert C. Kurtz, Donald A. Barkauskas, Steven Gallinger, Junwen Wang, Simina M. Boca, Irene L. Andrulis, Hongbing Shen, Adrienne M. Flanagan, Cosmeri Rizzato, Marianna C. Stern, Angela Carta, Melissa C. Southey, Corrado Magnani, Sook Whan Sung, Lesley F. Tinker, M. Dorronsoro, Guangfu Jin, Giovanna Masala, Yi-Long Wu, Min-Ho Shin, Ming Shyan Huang, Göran Hallmans, Xueying Zhao, Jacques Riby, Beatrice Melin, Adonina Tardón, Börje Ljungberg, Mark Liebow, Elizabeth A. Holly, Carol Giffen, Paolo Boffetta, Maria Fernanda Amary, Jihua Li, Mazda Jenab, Keitaro Matsuo, Nalan Gokgoz, Karin E. Smedby, Cari M. Kitahara, Mia M. Gaudet, Cecilia Arici, Brian E. Henderson, Amy Hutchinson, Elio Riboli, Patricia Hartge, Victoria K. Cortessis, Kexin Chen, Dalsu Baris, Michael Goggins, Young-Chul Kim, Tsung-Ying Yang, Fusheng Wei, Peter D. Inskip, Demetrius Albanes, Fang Yu Tsai, Qing Lan, Li Jin, Charles E. Lawrence, Nikolaus Becker, Rachael S. Stolzenberg-Solomon, Bengt Glimelius, Wei Hu, Maria Dolores Chirlaque, Kimberly A. Bertrand, Bruce K. Armstrong, Veronica Wendy Setiawan, Kathy J. Helzlsouer, Manal M. Hassan, Jun Yokota, David V. Conti, Kai Yu, Chenwei Liu, Christine F. Skibola, Jae Yong Park, Fernando Lecanda, Dimitrios Trichopoulos, Eleanor Kane, Dongxin Lin, Yun-Chul Hong, Consol Serra, Anne Tjønneland, Melissa A. Austin, X. Zhang, Charles S. Fuchs, Nathaniel Rothman, Paul Brennan, Chih-Liang Wang, Wei Shen, Ying-Huang Tsai, Hee Nam Kim, Ghislaine Scelo, Faith G. Davis, Sara Lindström, Molly Schwenn, Giuseppe Mastrangelo, Adeline Seow, Laufey T. Amundadottir, Laura E. Beane Freeman, Huan Guo, Victor Ho-Fun Lee, Aruna Kamineni, Pierluigi Cocco, Jiang Chang, Emanuele Angelucci, Paige M. Bracci, Yong-Bing Xiang, G. M. Monawar Hosain, Elisabete Weiderpass, James R. Cerhan, Junjie Wu, Lauren R. Teras, Jin Hee Kim, Qiuyin Cai, Sampson, J.N., Wheeler, W.A., Yeager, M., Panagiotou, O., Wang, Z., Berndt, S.I., Lan, Q., Abnet, C.C., Amundadottir, L.T., Figueroa, J.D., Landi, M.T., Mirabello, L., Savage, S.A., Taylor, P.R., De Vivo, I., McGlynn, K.A., Purdue, M.P., Rajaraman, P., Adami, H.-O., Ahlbom, A., Albanes, D., Amary, M.F., An, S.-J., Andersson, U., Andriole, G., Jr., Andrulis, I.L., Angelucci, E., Ansell, S.M., Arici, C., Armstrong, B.K., Arslan, A.A., Austin, M.A., Baris, D., Barkauskas, D.A., Bassig, B.A., Becker, N., Benavente, Y., Benhamou, S., Berg, C., Van Den Berg, D., Bernstein, L., Bertrand, K.A., Birmann, B.M., Black, A., Boeing, H., Boffetta, P., Boutron-Ruault, M.-C., Bracci, P.M., Brinton, L., Brooks-Wilson, A.R., Bueno-De-Mesquita, H.B., Burdett, L., Buring, J., Butler, M.A., Cai, Q., Cancel-Tassin, G., Canzian, F., Carrato, A., Carreon, T., Carta, A., Chan, J.K.C., Chang, E.T., Chang, G.-C., Chang, I.S., Chang, J., Chang-Claude, J., Chen, C.-J., Chen, C.-Y., Chen, C., Chen, C.-H., Chen, H., Chen, K., Chen, K.-Y., Chen, K.-C., Chen, Y., Chen, Y.-H., Chen, Y.-S., Chen, Y.-M., Chien, L.-H., Chirlaque, M.-D., Choi, J.E., Choi, Y.Y., Chow, W.-H., Chung, C.C., Clavel, J., Clavel-Chapelon, F., Cocco, P., Colt, J.S., Comperat, E., Conde, L., Connors, J.M., Conti, D., Cortessis, V.K., Cotterchio, M., Cozen, W., Crouch, S., Crous-Bou, M., Cussenot, O., Davis, F.G., Ding, T., Diver, W.R., Dorronsoro, M., Dossus, L., Duell, E.J., Ennas, M.G., Erickson, R.L., Feychting, M., Flanagan, A.M., Foretova, L., Fraumeni, J.F., Jr., Freedman, N.D., Freeman, L.E.B., Fuchs, C., Gago-Dominguez, M., Gallinger, S., Gao, Y.-T., Gapstur, S.M., Garcia-Closas, M., García-Closas, R., Gascoyne, R.D., Gastier-Foster, J., Gaudet, M.M., Gaziano, J.M., Giffen, C., Giles, G.G., Giovannucci, E., Glimelius, B., Goggins, M., Gokgoz, N., Goldstein, A.M., Gorlick, R., Gross, M., Grubb, R., III and Gu, J., Guan, P., Gunter, M., Guo, H., Habermann, T.M., Haiman, C.A., Halai, D., Hallmans, G., Hassan, M., Hattinger, C., He, Q., He, X., Helzlsouer, K., Henderson, B., Henriksson, R., Hjalgrim, H., Hoffman-Bolton, J., Hohensee, C., Holford, T.R., Holly, E.A., Hong, Y.-C., Hoover, R.N., Horn-Ross, P.L., Hosain, G.M.M., Hosgood, H.D., III and Hsiao, C.-F., Hu, N., Hu, W., Hu, Z., Huang, M.-S., Huerta, J.-M., Hung, J.-Y., Hutchinson, A., Inskip, P.D., Jackson, R.D., Jacobs, E.J., Jenab, M., Jeon, H.-S., Ji, B.-T., Jin, G., Jin, L., Johansen, C., Johnson, A., Jung, Y.J., Kaaks, R., Kamineni, A., Kane, E., Kang, C.H., Karagas, M.R., Kelly, R.S., Khaw, K.-T., Kim, C., Kim, H.N., Kim, J.H., Kim, J.S., Kim, Y.H., Kim, Y.T., Kim, Y.-C., Kitahara, C.M., Klein, A.P., Klein, R.J., Kogevinas, M., Kohno, T., Kolonel, L.N., Kooperberg, C., Kricker, A., Krogh, V., Kunitoh, H., Kurtz, R.C., Kweon, S.-S., La Croix, A., Lawrence, C., Lecanda, F., Lee, V.H.F., Li, D., Li, H., Li, J., Li, Y.-J., Li, Y., Liao, L.M., Liebow, M., Lightfoot, T., Lim, W.-Y., Lin, C.-C., Lin, D., Lindstrom, S., Linet, M.S., Link, B.K., Liu, C., Liu, J., Liu, L., Ljungberg, B., Lloreta, J., Di Lollo, S., Lu, D., Lund, E., Malats, N., Mannisto, S., Marchand, L.L., Marina, N., Masala, G., Mastrangelo, G., Matsuo, K., Maynadie, M., McKay, J., McKean-Cowdin, R., Melbye, M., Melin, B.S., Michaud, D.S., Mitsudomi, T., Monnereau, A., Montalvan, R., Moore, L.E., Mortensen, L.M., Nieters, A., North, K.E., Novak, A.J., Oberg, A.L., Offit, K., Oh, I.-J., Olson, S.H., Palli, D., Pao, W., Park, I.K., Park, J.Y., Park, K.H., Patiño-Garcia, A., Pavanello, S., Peeters, P.H.M., Perng, R.-P., Peters, U., Petersen, G.M., Picci, P., Pike, M.C., Porru, S., Prescott, J., Prokunina-Olsson, L., Qian, B., Qiao, Y.-L., Rais, M., Riboli, E., Riby, J., Risch, H.A., Rizzato, C., Rodabough, R., Roman, E., Roupret, M., Ruder, A.M., De Sanjose, S., Scelo, G., Schned, A., Schumacher, F., Schwartz, K., Schwenn, M., Scotlandi, K., Seow, A., Serra, C., Serra, M., Sesso, H.D., Setiawan, V.W., Severi, G., Severson, R.K., Shanafelt, T.D., Shen, H., Shen, W., Shin, M.-H., Shiraishi, K., Shu, X.-O., Siddiq, A., Sierrasesúmaga, L., Sihoe, A.D.L., Skibola, C.F., Smith, A., Smith, M.T., Southey, M.C., Spinelli, J.J., Staines, A., Stampfer, M., Stern, M.C., Stevens, V.L., Stolzenberg-Solomon, R.S., Su, J., Su, W.-C., Sund, M., Sung, J.S., Sung, S.W., Tan, W., Tang, W., Tardón, A., Thomas, D., Thompson, C.A., Tinker, L.F., Tirabosco, R., Tjønneland, A., Travis, R.C., Trichopoulos, D., Tsai, F.-Y., Tsai, Y.-H., Tucker, M., Turner, J., Vajdic, C.M., Vermeulen, R.C.H., Villano, D.J., Vineis, P., Virtamo, J., Visvanathan, K., Wactawski-Wende, J., Wang, C., Wang, C.-L., Wang, J.-C., Wang, J., Wei, F., Weiderpass, E., Weiner, G.J., Weinstein, S., Wentzensen, N., White, E., Witzig, T.E., Wolpin, B.M., Wong, M.P., Wu, C., Wu, G., Wu, J., Wu, T., Wu, W., Wu, X., Wu, Y.-L., Wunder, J.S., Xiang, Y.-B., Xu, J., Xu, P., Yang, P.-C., Yang, T.-Y., Ye, Y., Yin, Z., Yokota, J., Yoon, H.-I., Yu, C.-J., Yu, H., Yu, K., Yuan, J.-M., Zelenetz, A., Zeleniuch-Jacquotte, A., Zhang, X.-C., Zhang, Y., Zhao, X., Zhao, Z., Zheng, H., Zheng, T., Zheng, W., Zhou, B., Zhu, M., Zucca, M., Boca, S.M., Cerhan, J.R., Ferri, G.M., Hartge, P., Hsiung, C.A., Magnani, C., Miligi, L., Morton, L.M., Smedby, K.E., Teras, L.R., Vijai, J., Wang, S.S., Brennan, P., Caporaso, N.E., Hunter, D.J., Kraft, P., Rothman, N., Silverman, D.T., Slager, S.L., Chanock, S.J., Chatterjee, N., Infection & Immunity, dIRAS RA-I&I RA, LS IRAS EEPI GRA (Gezh.risico-analyse), and Risk Assessment

Subjects
Male, Cancer Research, Lung Neoplasms, Lymphoma, Genome-wide association study, Polymorphism (computer science), Neoplasms, Medicine, Chronic, Genetics, Osteosarcoma, Oncology And Carcinogenesis, Leukemia, Smoking, Family aggregation, Single Nucleotide, Middle Aged, Familial risk, Diffuse, Kidney Neoplasms, Lymphocytic, Oncology, Adult, Aged, Asian Continental Ancestry Group, Bone Neoplasms, European Continental Ancestry Group, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Polymorphism, Single Nucleotide, Testicular Neoplasms, Tissue Array Analysis, Urinary Bladder Neoplasms, Genetic Predisposition to Disease, Genome-Wide Association Study, Genetic correlation, Large B-Cell, Oncology & Carcinogenesis, Polymorphism, business.industry, Extramural, B-Cell, Cancer, Heritability, Genome-wide association studies for thirteen cancer types, medicine.disease, business
Abstract

BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.RESULTS: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.CONCLUSION: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.

Published
2015

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