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1. HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes

Author

Wang, Sophia S., primary, Carrington, Mary, additional, Berndt, Sonja I., additional, Slager, Susan L., additional, Bracci, Paige M., additional, Voutsinas, Jenna, additional, Cerhan, James R., additional, Smedby, Karin E., additional, Hjalgrim, Henrik, additional, Vijai, Joseph, additional, Morton, Lindsay M., additional, Vermeulen, Roel, additional, Paltiel, Ora, additional, Vajdic, Claire M., additional, Linet, Martha S., additional, Nieters, Alexandra, additional, de Sanjose, Silvia, additional, Cozen, Wendy, additional, Brown, Elizabeth E., additional, Turner, Jennifer, additional, Spinelli, John J., additional, Zheng, Tongzhang, additional, Birmann, Brenda M., additional, Flowers, Christopher R., additional, Becker, Nikolaus, additional, Holly, Elizabeth A., additional, Kane, Eleanor, additional, Weisenburger, Dennis, additional, Maynadie, Marc, additional, Cocco, Pierluigi, additional, Albanes, Demetrius, additional, Weinstein, Stephanie J., additional, Teras, Lauren R., additional, Diver, W. Ryan, additional, Lax, Stephanie J., additional, Travis, Ruth C., additional, Kaaks, Rudolph, additional, Riboli, Elio, additional, Benavente, Yolanda, additional, Brennan, Paul, additional, McKay, James, additional, Delfau-Larue, Marie-Hélène, additional, Link, Brian K., additional, Magnani, Corrado, additional, Ennas, Maria Grazia, additional, Latte, Giancarlo, additional, Feldman, Andrew L., additional, Doo, Nicole Wong, additional, Giles, Graham G., additional, Southey, Melissa C., additional, Milne, Roger L., additional, Offit, Kenneth, additional, Musinsky, Jacob, additional, Arslan, Alan A., additional, Purdue, Mark P., additional, Adami, Hans-Olov, additional, Melbye, Mads, additional, Glimelius, Bengt, additional, Conde, Lucia, additional, Camp, Nicola J., additional, Glenn, Martha, additional, Curtin, Karen, additional, Clavel, Jacqueline, additional, Monnereau, Alain, additional, Cox, David G., additional, Ghesquières, Hervé, additional, Salles, Gilles, additional, Bofetta, Paulo, additional, Foretova, Lenka, additional, Staines, Anthony, additional, Davis, Scott, additional, Severson, Richard K., additional, Lan, Qing, additional, Brooks-Wilson, Angela, additional, Smith, Martyn T., additional, Roman, Eve, additional, Kricker, Anne, additional, Zhang, Yawei, additional, Kraft, Peter, additional, Chanock, Stephen J., additional, Rothman, Nathaniel, additional, Hartge, Patricia, additional, and Skibola, Christine F., additional

Published
2018
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7. HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes

Author

Roel Vermeulen, Paulo Bofetta, Nicole Wong Doo, Mark P. Purdue, Eleanor Kane, Gilles Salles, Bengt Glimelius, Christine F. Skibola, Tongzhang Zheng, Graham G. Giles, Scott Davis, Pierluigi Cocco, Karin E. Smedby, Melissa C. Southey, Alexandra Nieters, Elizabeth A. Holly, Corrado Magnani, Paul Brennan, Stephanie J. Lax, David G. Cox, Lindsay M. Morton, Nikolaus Becker, Qing Lan, Elio Riboli, Herve Ghesquieres, Rudolph Kaaks, Jennifer Turner, Martha S. Linet, Anne Kricker, Stephanie J. Weinstein, Christopher R. Flowers, Alain Monnereau, Silvia de Sanjosé, Mary Carrington, John J. Spinelli, Patricia Hartge, Nathaniel Rothman, Yolanda Benavente, Susan L. Slager, Martha Glenn, Richard K. Severson, Ora Paltiel, Yawei Zhang, Ruth C. Travis, Demetrius Albanes, Nicola J. Camp, Paige M. Bracci, Jacqueline Clavel, James R. Cerhan, Marc Maynadié, Maria Grazia Ennas, Marie Hélène Delfau-Larue, Peter Kraft, Henrik Hjalgrim, Roger L. Milne, Alan A. Arslan, Jacob Musinsky, Martyn T. Smith, Anthony Staines, Lauren R. Teras, Jenna M. Voutsinas, Lenka Foretova, Sophia S. Wang, Hans-Olov Adami, Andrew L. Feldman, Wendy Cozen, Angela Brooks-Wilson, Kenneth Offit, Brian K. Link, Brenda M. Birmann, Sonja I. Berndt, Stephen J. Chanock, James McKay, Dennis D. Weisenburger, Claire M. Vajdic, Giancarlo Latte, Karen Curtin, W. Ryan Diver, Mads Melbye, Lucia Conde, Elizabeth E. Brown, Joseph Vijai, Eve Roman, Wang, Sophia S., Carrington, Mary, Berndt, Sonja I., Slager, Susan L., Bracci, Paige M., Voutsinas, Jenna, Cerhan, James R., Smedby, Karin E., Hjalgrim, Henrik, Vijai, Joseph, Morton, Lindsay M., Vermeulen, Roel, Paltiel, Ora, Vajdic, Claire M., Linet, Martha S., Nieters, Alexandra, de Sanjose, Silvia, Cozen, Wendy, Brown, Elizabeth E., Turner, Jennifer, Spinelli, John J., Zheng, Tongzhang, Birmann, Brenda M., Flowers, Christopher R., Becker, Nikolau, Holly, Elizabeth A., Kane, Eleanor, Weisenburger, Denni, Maynadie, Marc, Cocco, Pierluigi, Albanes, Demetriu, Weinstein, Stephanie J., Teras, Lauren R., Diver, W. Ryan, Lax, Stephanie J., Travis, Ruth C., Kaaks, Rudolph, Riboli, Elio, Benavente, Yolanda, Brennan, Paul, McKay, Jame, Delfau-Larue, Marie-Hélène, Link, Brian K., Magnani, Corrado, Ennas, Maria Grazia, Latte, Giancarlo, Feldman, Andrew L., Doo, Nicole Wong, Giles, Graham G., Southey, Melissa C., Milne, Roger L., Offit, Kenneth, Musinsky, Jacob, Arslan, Alan A., Purdue, Mark P., Adami, Hans-Olov, Melbye, Mad, Glimelius, Bengt, Conde, Lucia, Camp, Nicola J., Glenn, Martha, Curtin, Karen, Clavel, Jacqueline, Monnereau, Alain, Cox, David G., Ghesquières, Hervé, Salles, Gille, Boffetta, Paolo, Foretova, Lenka, Staines, Anthony, Davis, Scott, Severson, Richard K., Lan, Qing, Brooks-Wilson, Angela, Smith, Martyn T., Roman, Eve, Kricker, Anne, Zhang, Yawei, Kraft, Peter, Chanock, Stephen J., Rothman, Nathaniel, Hartge, Patricia, and Skibola, Christine F.

Subjects
Male, 0301 basic medicine, Heterozygote, Cancer Research, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Chronic lymphocytic leukemia, EPIDEMIOLOGIC RESEARCH, Genome-wide association study, Human leukocyte antigen, Biology, CLASSIFICATION, ANTIGENS, Article, Genetic Heterogeneity, 03 medical and health sciences, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, INTERLYMPH, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Prospective Studies, GENOME-WIDE ASSOCIATION, Allele, HLA Complex, Science & Technology, Hematology, CHRONIC LYMPHOCYTIC-LEUKEMIA, Genetic heterogeneity, Lymphoma, Non-Hodgkin, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, HETEROZYGOTE ADVANTAGE, medicine.disease, 3. Good health, Lymphoma, 030104 developmental biology, Oncology, Case-Control Studies, Immunology, B-VIRUS INFECTION, Female, Life Sciences & Biomedicine, NEOPLASMS, Genome-Wide Association Study
Abstract

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086–96. ©2018 AACR.

Published
2018

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