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1. 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
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2. O04-4 Household pesticides and risk of lymphoma subtypes

Author

Carlo Aresti, Fahad Ahmed, Maria Grazia Ennas, Giannina Satta, Emanuele Angelucci, Pierluigi Cocco, Michela Ursi, Marco Rais, Marcello Noli, Marcello Campagna, Attilio Gabbas, Federico Marras, and Elisabetta Garofalo

Subjects
Pyrethroid, business.industry, Pesticide, Logistic regression, medicine.disease, Lymphoma, Toxicology, chemistry.chemical_compound, Quartile, chemistry, hemic and lymphatic diseases, Environmental health, Etiology, Medicine, Rural area, business, Multiple myeloma
Abstract

Background Evidence from recent studies provides support to the link between exposure to certain pesticide classes and risk of non Hodgkin lymphoma and its subtypes. Whether use of insecticides in the household is also associated with an increased risk is unclear. Methods During 1998–2004, a case-control study on the aetiology of lymphoma was conducted Sardinia, Italy as part of the European multicentre study EPILYMPH. Information on use of insecticides in the household over the residential history of study subjects was collected using a standardised questionnaire. Risk of the major lymphoma subtypes associated with ever use of insecticides indoor and with quartiles of days/year of use was calculated with unconditional logistic regression analysis, adjusting by age, gender, education and study centre. Results Risk of lymphoma overall and B-cell lymphoma was not associated with ever use of indoor insecticide in the household (OR = 0.8, 95% CI: 0.6–1.0), neither we observed an increase in risk associated with increasing quartiles of days/year of indoor use of insecticides: risk in the upper quartile was OR = 0.8 (95% CI: 0.5–1.3) for all lymphomas and OR = 0.8 (95% CI: 0.5–1.4) for B-cell lymphoma. Results were consistent across the major lymphoma subtypes, but multiple myeloma, which showed a modest non significant association, difficult to interpret because of the small number of cases. Conclusions Pyrethroid and carbamate insecticides have been extensively used in different forms as indoor insecticides, particularly in rural areas or nearby water basins. Our results suggest no association between risk of the major lymphoma subtypes and prolonged indoor use of insecticides.

Published
2016
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3. P228 Recreational physical activity and risk of lymphoma subtypes

Author

Roberto Loscerbo, Ilaria Pilia, Marco Rais, Alessandra Argiolas, Emanuele Angelucci, Diego Serraino, Pierluigi Cocco, Fahad Ahmed, Luigi Isaia Lecca, Giannina Satta, Marcello Campagna, Sergio Pili, Attilio Gabbas, Federico Meloni, Tiziana Serra, Maria Grazia Ennas, and Nicola Mascia

Subjects
Oncology, medicine.medical_specialty, business.industry, Follicular lymphoma, Cancer, medicine.disease, Logistic regression, Lymphoma, Quality of life, hemic and lymphatic diseases, Internal medicine, Immunology, Etiology, Medicine, business, Diffuse large B-cell lymphoma, Multiple myeloma
Abstract

Background Physical activity is known to protect against several cancers and to improve survival and quality of life in cancer patients. Few studies have addressed the association between physical activity and risk of non Hodgkin lymphoma and its subtypes. Methods During 1998–2004, a case-control study on the aetiology of lymphoma was conducted Sardinia, Italy as part of the European multicentre study EPILYMPH. Information on lifetime recreational physical activity was collected using a standardised questionnaire. Risk of the major lymphoma subtypes associated with ever practicing physical activity and with quartiles of hours of recreational physical activity in the lifetime was calculated with unconditional logistic regression analysis, adjusting by age, gender, education and study centre. Results Risk of lymphoma overall and B-cell lymphoma was not associated with ever practicing recreational physical activity (OR = 0.9, 95% CI: 0.7–1.3). However, a significant protective effect was observed in the upper quartile of hours of recreational physical activity in the lifetime (OR = 0.4, 95% CI: 0.3–0.8). The inverse association was consistent across the major lymphoma subtypes, namely diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia, and multiple myeloma. Conclusions Our results suggest an inverse association between risk of the major lymphoma subtypes and prolonged recreational physical activity.

Published
2016
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4. P028 Risk of lymphoma subtypes and occupational exposure to organic dust

Author

Alexandra Nieters, Marco Rais, Roberto Loscerbo, Tiziana Serra, Maria Grazia Ennas, Attilio Gabbas, Federico Marras, Michela Ursi, Marcello Noli, Lenka Foretova, Alessandra Argiolas, Giannina Satta, Ilaria Pilia, Nicola Mascia, Emanuele Angelucci, Anthony Staines, Diego Serraino, Fahad Ahmed, Carlo Aresti, Luigi Isaia Lecca, Marc Maynadié, Sergio Pili, Pierluigi Cocco, Nikolaus Becker, T Nonne, and Silvia de Sanjosé

Subjects
Organic dust, Inverse Association, Lymphocytic leukaemia, business.industry, Follicular lymphoma, Mineralogy, medicine.disease, Logistic regression, complex mixtures, 3. Good health, Lymphoma, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Environmental health, medicine, 030212 general & internal medicine, Occupational exposure, business, Diffuse large B-cell lymphoma
Abstract

Background Exposure to high molecular weight agents, such as those associated with organic dust, has shown an inverse association with lymphoma risk. In this paper, we used the data base of the multicentre European case-control study EPILYMPH to explore risk of lymphoma subtypes associated with occupational exposure to six different types of organic dust. Methods During 1998–2004, a case-control study on the aetiology of lymphoma was conducted in six European countries. Overall, assessment of exposure to organic dust was completed in 1941 cases and 1992 controls. Risk of the major lymphoma subtypes associated with exposure to any organic dust, flour dust, hardwood, softwood, leather and natural and artificial textile fibres was calculated with unconditional logistic regression analysis, adjusting by age, gender, education and study centre. Results Risk of B-cell lymphoma associated with exposure to any organic dust was inverse (OR = 0.6, 95% CI: 0.3–1.0), with a significant inverse trend by duration and intensity of exposure. The inverse association was strongest for exposure to flour and wood dust, independent on whether hardwood or softwood. The inverse association was likewise observed ifor diffuse large B cell lymphoma, follicular lymphoma, and chronic lymphocytic leukaemia. Conclusions Our results appear to confirm an inverse association of risk of the major lymphoma subtypes with exposure to organic dust, and aprticularly with flour dust and wood dust.

Published
2016
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5. Prevalence of Oncogenic HPV Types in Sardinia (Italy): Implications for the Impact of Prophylactic Anti-HPV Vaccines

Author

Sergio Laconi, Sabrina Pitzalis, Stefania Montisci, Marianna Greco, Alberto Orani, and Marco Rais

Subjects
Gynecology, Oncology, Cervical cancer, medicine.medical_specialty, education.field_of_study, Hpv types, business.industry, Population, virus diseases, HPV vaccines, Malignancy, medicine.disease, female genital diseases and pregnancy complications, Hpv prevalence, Clinical trial, Infectious Diseases, Internal medicine, medicine, Adenocarcinoma, education, business
Abstract

Infection with high-risk HPV genotypes is considered an essential step in cervical carcinogenesis. Recently, prophylactic anti-HPV vaccines have shown to provide effective protection in clinical trials. However, protection appears to be type-restricted, thus, its real extent will depend on HPV types prevalence in the target population. Here we report HPV prevalence in 555 Italian women with various stages of HPV-related cervical disease (343 CIN1/L-SIL, 156 CIN2-3/HIGH-SIL, 43 invasive squamous cervical carcinoma and 13 adenocarcinoma), as well as in 315 women with smears negative for intraepithelial lesions or malignancy (NIL). HPV was found in 50.7% of CIN1/L-SIL, 87.2% of CIN2-3/HIGH-SIL, 97.7% of squamous carcinomas, 69.2% of adenocarcinomas and in 29.5% of NIL. HPV 16 was present in 69.0% of squamous carcinomas, 58.8% of CIN2-3/HIGH-SIL, in 22.9 and 16.1% of CIN1/L-SIL and NIL, respectively. HPV 18 was found in 7.3% and 4.8%, respectively, while in 35.3% and 26.2% of CIN2-3/HIGH-SIL and invasive carcinomas, respectively, were present high-risk HPV types other than type 16 and 18. Based on these data, it is expected that current HPV prophylactic vaccines could effectively prevent up to 70% of invasive cervical cancers and a slightly smaller proportion of high-grade lesions, in our population.

Published
2007
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6. Risk of lymphoma subtypes and dietary habits in a Mediterranean area

Author

Sonia Sanna, Marcello Campagna, Mariagrazia Zucca, Maria Grazia Ennas, Marco Rais, Pierluigi Cocco, Antonella Uras, Emanuele Angelucci, Gian Carlo Latte, and Attilio Gabbas

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Mediterranean diet, Lymphoma, Epidemiology, Population, Follicular lymphoma, Risk Factors, hemic and lymphatic diseases, Surveys and Questionnaires, medicine, Humans, education, Aged, education.field_of_study, business.industry, Case-control study, Odds ratio, Middle Aged, medicine.disease, Diet, Oncology, Italy, Case-Control Studies, Immunology, Female, business, Diffuse large B-cell lymphoma, Body mass index, Demography
Abstract

Background Previous studies have suggested that diet might affect risk of lymphoma subtypes. We investigated risk of lymphoma and its major subtypes associated with diet in the Mediterranean island of Sardinia, Italy. Methods In 1998–2004, 322 incident lymphoma cases and 446 randomly selected population controls participated in a case-control study on lymphoma etiology in central-southern Sardinia. Questionnaire interviews included frequency of intake of 112 food items. Risk associated with individual dietary items and groups thereof was explored by unconditional and polytomous logistic regression analysis, adjusting by age, gender and education. Results We observed an upward trend in risk of lymphoma (all subtypes combined) and B-cell lymphoma with frequency of intake of well done grilled/roasted chicken ( p for trend=0.01), and pizza ( p for trend=0.047), Neither adherence to Mediterranean diet nor a frequent intake of its individual components conveyed protection. We detected heterogeneity in risk associated with several food items and groups thereof by lymphoma subtypes although we could not rule out chance as responsible for the observed direct or inverse associations. Conclusions Adherence to a Mediterranean diet does not seem to convey protection against the development of lymphoma. The association with specific food items might vary by lymphoma subtype.

Published
2014

7. Household contact with pets and birds and risk of lymphoma

Author

Saverio Bellizzi, Mariagrazia Zucca, Pierluigi Cocco, I D’Andrea, Maria Monne, Attilio Gabbas, Simonetta Sesler, Emanuele Angelucci, Maria Grazia Ennas, Antonella Uras, Dorothea Nitsch, Giovanna Piras, Marco Rais, and Angela Onida

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Household contact, Lymphoma, medicine.medical_treatment, Population, Animal-assisted therapy, Birds, Risk Factors, hemic and lymphatic diseases, Internal medicine, Epidemiology, medicine, Animals, Humans, education, Aged, education.field_of_study, Family Characteristics, Hematology, business.industry, Human-Animal Bond, Odds ratio, Pets, Middle Aged, medicine.disease, Confidence interval, Oncology, Animals, Domestic, Case-Control Studies, Immunology, Female, business, Demography
Abstract

Contact with household pets has been suggested to be inversely associated with lymphoma risk. We tested the hypothesis in a case–control study of lymphoma in the Sardinia region of Italy. Cases were 326 patients, first diagnosed with lymphoma in 1999–2003. Controls were 464 population controls, frequency matched to cases by age, gender, and area of residence. In person interviews included self-reported household contact with pets and birds, type of pet(s), and age at starting contact. Frequent contact with birds was inversely associated with lymphoma, and particularly B-cell non-Hodgkin lymphoma (odds ratio [OR] = 0.6, 95% confidence interval [95% CI]: 0.4, 0.9). Contact with chickens accounted for this inverse association, which was strongest for first contact occurring at age ≤8 years (OR = 0.4, 95% CI: 0.2, 1.0). No association was observed when first contact occurred at age 9 or older. Contact with any pets was inversely associated with risk of diffuse large B-cell lymphoma (OR = 0.4, 95% CI: 0.2, 1.0), but not other lymphoma subtypes. Our results support the hypothesis that early-life exposure to pets, birds and particularly with chickens might be associated with a reduced risk of lymphoma.

Published
2010

8. Risk of malignant lymphoma following viral hepatitis infection

Author

Angelo D. Palmas, Marco Rais, Antonella Uras, Maria Giuseppina Cabras, Stefania Collu, Emanuele Angelucci, Massimo Melis, Maria Monne, M. G. Ennas, Pierluigi Cocco, Giovannino Massarelli, Giovanna Piras, Marco Murineddu, Attilio Gabbas, Pierfelice Todde, and Alexandra Nieters

Subjects
Adult, Male, medicine.medical_specialty, Hepatitis C virus, Follicular lymphoma, medicine.disease_cause, Gastroenterology, Risk Factors, Internal medicine, Surveys and Questionnaires, medicine, Humans, Risk factor, Aged, Retrospective Studies, Hepatitis, business.industry, Lymphoma, Non-Hodgkin, Hematology, Hepatitis C, Odds ratio, Hepatitis B, Hepatitis C, Chronic, Middle Aged, medicine.disease, Italy, Immunology, Female, business, Viral hepatitis
Abstract

We investigated lymphoma risk following hepatitis infection in a case-control study of 274 incident lymphoma cases, defined according to the WHO classification, and 336 population controls in Sardinia, Italy. Part of our study population (198 cases and 219 controls) was included in the EPILYMPH study of Hepatitis C virus (HCV) infection in relation to non-Hodgklin’s lymphoma risk. Based on questionnaire information on whether and at what age a diagnosis of hepatitis was posed by a physician, systematic anti-HCV antibodies testing in cases and controls by enzyme-linked immunoassay, and HCV-RNA assessment by PCR analyses in positive samples, we investigated more in detail whether hepatitis non-C is also associated with lymphoma risk, and whether risk varies by clinical form of hepatitis (acute or chronic infection). After adjusting by age, gender, education, and area of birth whether from the study area or elsewhere in Italy, a previous generic diagnosis of hepatitis was associated with a significantly elevated lymphoma risk [odds ratio (OR) = 1.8; 95% CI 1.1, 2.8], which was equally increased for hepatitis B (OR = 1.8; 95% CI 0.9, 3.5), for HCV positive subjects overall (OR = 2.0; 95% CI 0.8, 4.8), and for hepatitis non-B non-C (OR = 1.6; 95% CI 0.7, 3.9). Once concurrent infection from other hepatitis viruses was excluded, acute or chronic hepatitis C was the only one showing a consistent risk increase in all lymphoma subtypes, but follicular lymphoma. Some indications of an excess risk of lymphoma were observed also for acute, but not chronic forms of hepatitis B and hepatitis non-B, non C. Self-limited hepatitis C did not show an association. No significant heterogeneity in the risk of major lymphoma subtype was observed. Our results confirm a role of either acute or chronic active HCV infection in lymphomagenesis. Further studies are warranted to test the hypothesis that acute infection from other hepatitis viruses might also increase lymphoma risk.

Published
2007

9. 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. 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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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