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

Author

Moore, A., Kane, E., 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., 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., Ghesquières, 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., 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., Berndt, S.I., IRAS OH Epidemiology Chemical Agents, and dIRAS RA-2

Subjects
follicular lymphoma, non-Hodgkin lymphoma, polygenic risk score, diffuse large B-celllymphoma, chronic lymphocytic leukemia, genetics, marginal zone lymphoma, 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

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

Author

IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Moore, A., Kane, E., 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., 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., Ghesquières, 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., 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., Berndt, S.I., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Moore, A., Kane, E., 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., 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., Ghesquières, 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., 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.

Published
2020

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

Author

Moore, A, Kane, E, Wang, Z, Panagiotou, OA, Teras, LR, Monnereau, A, Wong Doo, N, Machiela, MJ, Skibola, CF, Slager, SL, Salles, G, Camp, NJ, Bracci, PM, Nieters, A, Vermeulen, RCH, Vijai, J, Smedby, KE, Zhang, Y, Vajdic, CM, Cozen, W, Spinelli, JJ, Hjalgrim, H, Giles, GG, Link, BK, Clavel, J, Arslan, AA, Purdue, MP, Tinker, LF, Albanes, D, Ferri, GM, Habermann, TM, Adami, H-O, Becker, N, Benavente, Y, Bisanzi, S, Boffetta, P, Brennan, P, Brooks-Wilson, AR, Canzian, F, Conde, L, Cox, DG, Curtin, K, Foretova, L, Gapstur, SM, Ghesquieres, H, Glenn, M, Glimelius, B, Jackson, RD, Lan, Q, Liebow, M, Maynadie, M, McKay, J, Melbye, M, Miligi, L, Milne, RL, Molina, TJ, Morton, LM, North, KE, Offit, K, Padoan, M, Patel, AV, Piro, S, Ravichandran, V, Riboli, E, de Sanjose, S, Severson, RK, Southey, MC, Staines, A, Stewart, C, Travis, RC, Weiderpass, E, Weinstein, S, Zheng, T, Chanock, SJ, Chatterjee, N, Rothman, N, Birmann, BM, Cerhan, JR, Berndt, SI, Moore, A, Kane, E, Wang, Z, Panagiotou, OA, Teras, LR, Monnereau, A, Wong Doo, N, Machiela, MJ, Skibola, CF, Slager, SL, Salles, G, Camp, NJ, Bracci, PM, Nieters, A, Vermeulen, RCH, Vijai, J, Smedby, KE, Zhang, Y, Vajdic, CM, Cozen, W, Spinelli, JJ, Hjalgrim, H, Giles, GG, Link, BK, Clavel, J, Arslan, AA, Purdue, MP, Tinker, LF, Albanes, D, Ferri, GM, Habermann, TM, Adami, H-O, Becker, N, Benavente, Y, Bisanzi, S, Boffetta, P, Brennan, P, Brooks-Wilson, AR, Canzian, F, Conde, L, Cox, DG, Curtin, K, Foretova, L, Gapstur, SM, Ghesquieres, H, Glenn, M, Glimelius, B, Jackson, RD, Lan, Q, Liebow, M, Maynadie, M, McKay, J, Melbye, M, Miligi, L, Milne, RL, Molina, TJ, Morton, LM, North, KE, Offit, K, Padoan, M, Patel, AV, Piro, S, Ravichandran, V, Riboli, E, de Sanjose, S, Severson, RK, Southey, MC, Staines, A, Stewart, C, Travis, RC, Weiderpass, E, Weinstein, S, Zheng, T, Chanock, SJ, Chatterjee, N, Rothman, N, Birmann, BM, Cerhan, JR, and Berndt, SI

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

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

Author

Din, L., Sheikh, M., Kosaraju, N., Smedby, K.E., Bernatsky, S., Berndt, S.I., Skibola, C.F., Nieters, A., McKay, J.D., Cocco, P., Maynadié, M., Foretová, L., Staines, A., Mack, T.M., de Sanjosé, S., Vyse, T.J., Padyukov, L., Monnereau, A., Arslan, A.A., Moore, A., Brooks-Wilson, A.R., 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., Ghesquières, H., De Vivo, I., Clavel, J., Cerhan, J.R., Spinelli, J.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., Benavente, Y., Taub, Z., Madireddy, L., Gourraud, P.-A., Oksenberg, J.R., Cozen, W., Hjalgrim, H., Khankhanian, P., Din, L., Sheikh, M., Kosaraju, N., Smedby, K.E., Bernatsky, S., Berndt, S.I., Skibola, C.F., Nieters, A., McKay, J.D., Cocco, P., Maynadié, M., Foretová, L., Staines, A., Mack, T.M., de Sanjosé, S., Vyse, T.J., Padyukov, L., Monnereau, A., Arslan, A.A., Moore, A., Brooks-Wilson, A.R., 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., Ghesquières, H., De Vivo, I., Clavel, J., Cerhan, J.R., Spinelli, J.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., Benavente, Y., Taub, Z., Madireddy, L., Gourraud, P.-A., Oksenberg, J.R., Cozen, W., Hjalgrim, H., and Khankhanian, P.

Abstract

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

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

Author

Din, L, Sheikh, M, Kosaraju, N, Smedby, KE, Bernatsky, S, Berndt, S, Skibola, CF, Nieters, A, Wang, S, McKay, JD, Cocco, P, Maynadie, M, Foretova, L, Staines, A, Mack, TM, de Sanjose, S, Vyse, TJ, Padyukov, L, Monnereau, A, Arslan, AA, Moore, A, Brooks-Wilson, AR, Novak, AJ, Glimelius, B, Birmann, BM, Link, BK, Stewart, C, Vajdic, CM, Haioun, C, Magnani, C, Conti, D, Cox, DG, Casabonne, D, Albanes, D, Kane, E, Roman, E, Muzi, G, Salles, G, Giles, GG, Adami, H-O, Ghesquieres, H, De Vivo, I, Clavel, J, Cerhan, JR, Spinelli, JJ, Hofmann, J, Vijai, J, Curtin, K, Costenbader, KH, Onel, K, Offit, K, Teras, LR, Morton, L, Conde, L, Miligi, L, Melbye, M, Ennas, MG, Liebow, M, Purdue, MP, Glenn, M, Southey, MC, Din, M, Rothman, N, Camp, NJ, Doo, NW, Becker, N, Pradhan, N, Bracci, PM, Boffetta, P, Vineis, P, Brennan, P, Kraft, P, Lan, Q, Severson, RK, Vermeulen, RCH, Milne, RL, Kaaks, R, Travis, RC, Weinstein, SJ, Chanock, SJ, Ansell, SM, Slager, SL, Zheng, T, Zhang, Y, Benavente, Y, Taub, Z, Madireddy, L, Gourraud, P-A, Oksenberg, JR, Cozen, W, Hjalgrim, H, Khankhanian, P, Din, L, Sheikh, M, Kosaraju, N, Smedby, KE, Bernatsky, S, Berndt, S, Skibola, CF, Nieters, A, Wang, S, McKay, JD, Cocco, P, Maynadie, M, Foretova, L, Staines, A, Mack, TM, de Sanjose, S, Vyse, TJ, Padyukov, L, Monnereau, A, Arslan, AA, Moore, A, Brooks-Wilson, AR, Novak, AJ, Glimelius, B, Birmann, BM, Link, BK, Stewart, C, Vajdic, CM, Haioun, C, Magnani, C, Conti, D, Cox, DG, Casabonne, D, Albanes, D, Kane, E, Roman, E, Muzi, G, Salles, G, Giles, GG, Adami, H-O, Ghesquieres, H, De Vivo, I, Clavel, J, Cerhan, JR, Spinelli, JJ, Hofmann, J, Vijai, J, Curtin, K, Costenbader, KH, Onel, K, Offit, K, Teras, LR, Morton, L, Conde, L, Miligi, L, Melbye, M, Ennas, MG, Liebow, M, Purdue, MP, Glenn, M, Southey, MC, Din, M, Rothman, N, Camp, NJ, Doo, NW, Becker, N, Pradhan, N, Bracci, PM, Boffetta, P, Vineis, P, Brennan, P, Kraft, P, Lan, Q, Severson, RK, Vermeulen, RCH, Milne, RL, Kaaks, R, Travis, RC, Weinstein, SJ, Chanock, SJ, Ansell, SM, Slager, SL, Zheng, T, Zhang, Y, Benavente, Y, Taub, Z, Madireddy, L, Gourraud, P-A, Oksenberg, JR, Cozen, W, Hjalgrim, H, and Khankhanian, P

Abstract

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

7. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukemia

Author

Law, PJ, Berndt, SI, Speedy, HE, Camp, NJ, Sava, GP, Skibola, CF, Holroyd, A, Joseph, V, Sunter, NJ, Nieters, A, Bea, S, Monnereau, A, Martin-Garcia, D, Goldin, LR, Clot, G, Teras, LR, Quintela, I, Birmann, BM, Jayne, S, Cozen, W, Majid, A, Smedby, KE, Dearden, C, Brooks-Wilson, AR, Hall, AG, Purdue, MP, Mainou-Fowler, T, Vajdic, CM, Jackson, GH, Cocco, P, Marr, H, Zhang, Y, Zheng, T, Giles, GG, Lawrence, C, Call, TG, Liebow, M, Melbye, M, Glimelius, B, Mansouri, L, Glenn, M, Curtin, K, Diver, WR, Link, BK, Conde, L, Bracci, PM, Holly, EA, Jackson, RD, Tinker, LF, Benavente, Y, Boffetta, P, Brennan, P, Maynadie, M, McKay, J, Albanes, D, Weinstein, S, Wang, Z, Caporaso, NE, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Vermeulen, RCH, Southey, MC, Milne, RL, Clavel, J, Topka, S, Spinelli, JJ, Kraft, P, Grazia Ennas, M, Summerfield, G, Ferri, GM, Harris, RJ, Miligi, L, Pettitt, AR, North, KE, Allsup, DJ, Fraumeni, JF, Bailey, JR, Offit, K, Pratt, G, Hjalgrim, H, Pepper, C, Chanock, SJ, Fegan, C, Rosenquist, R, De Sanjose, S, Carracedo, A, Dyer, MJS, Catovsky, D, Campo, E, Cerhan, JR, Allan, JM, Rothman, N, Houlston, R, and Slager, S

Subjects
RISK, CHROMATIN, Science & Technology, LOCI, VARIANTS, DISEASE, Multidisciplinary Sciences, TRANSCRIPTION FACTORS, MD Multidisciplinary, IMPUTATION, Science & Technology - Other Topics, BREAST-CANCER, COMMON VARIATION, METAANALYSIS
Abstract

Several chronic lymphocytic leukemia (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 1000 Genomes and UK10K data, totaling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P = 5.04x10-13), 1q42.13 (rs41271473, P = 1.06x10-10), 4q24 (rs71597109, P = 1.37x10-10), 4q35.1 (rs57214277, P = 3.69x10-8), 6p21.31 (rs3800461, P = 1.97x10-8), 11q23.2 (rs61904987, P = 2.64x10-11), 18q21.1 (rs1036935, P = 3.27x10-8), 19p13.3 (rs7254272, P = 4.67x10-8) and 22q13.33 (rs140522, P = 2.70x10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for key determinants of B-cell development and immune response.

Published
2016

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

Author

Law, PJ, Berndt, SI, Speedy, HE, Camp, NJ, Sava, GP, Skibola, CF, Holroyd, A, Joseph, V, Sunter, NJ, Nieters, A, Bea, S, Monnereau, A, Martin-Garcia, D, Goldin, LR, Clot, G, Teras, LR, Quintela, I, Birmann, BM, Jayne, S, Cozen, W, Majid, A, Smedby, KE, Lan, Q, Dearden, C, Brooks-Wilson, AR, Hall, AG, Purdue, MP, Mainou-Fowler, T, Vajdic, CM, Jackson, GH, Cocco, P, Marr, H, Zhang, Y, Zheng, T, Giles, GG, Lawrence, C, Call, TG, Liebow, M, Melbye, M, Glimelius, B, Mansouri, L, Glenn, M, Curtin, K, Diver, WR, Link, BK, Conde, L, Bracci, PM, Holly, EA, Jackson, RD, Tinker, LF, Benavente, Y, Boffetta, P, Brennan, P, Maynadie, M, McKay, J, Albanes, D, Weinstein, S, Wang, Z, Caporaso, NE, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Vermeulen, RCH, Southey, MC, Milne, RL, Clavel, J, Topka, S, Spinelli, JJ, Kraft, P, Ennas, MG, Summerfield, G, Ferri, GM, Harris, RJ, Miligi, L, Pettitt, AR, North, KE, Allsup, DJ, Fraumeni, JF, Bailey, JR, Offit, K, Pratt, G, Hjalgrim, H, Pepper, C, Chanock, SJ, Fegan, C, Rosenquist, R, de Sanjose, S, Carracedo, A, Dyer, MJS, Catovsky, D, Campo, E, Cerhan, JR, Allan, JM, Rothman, N, Houlston, R, Slager, SL, Law, PJ, Berndt, SI, Speedy, HE, Camp, NJ, Sava, GP, Skibola, CF, Holroyd, A, Joseph, V, Sunter, NJ, Nieters, A, Bea, S, Monnereau, A, Martin-Garcia, D, Goldin, LR, Clot, G, Teras, LR, Quintela, I, Birmann, BM, Jayne, S, Cozen, W, Majid, A, Smedby, KE, Lan, Q, Dearden, C, Brooks-Wilson, AR, Hall, AG, Purdue, MP, Mainou-Fowler, T, Vajdic, CM, Jackson, GH, Cocco, P, Marr, H, Zhang, Y, Zheng, T, Giles, GG, Lawrence, C, Call, TG, Liebow, M, Melbye, M, Glimelius, B, Mansouri, L, Glenn, M, Curtin, K, Diver, WR, Link, BK, Conde, L, Bracci, PM, Holly, EA, Jackson, RD, Tinker, LF, Benavente, Y, Boffetta, P, Brennan, P, Maynadie, M, McKay, J, Albanes, D, Weinstein, S, Wang, Z, Caporaso, NE, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Vermeulen, RCH, Southey, MC, Milne, RL, Clavel, J, Topka, S, Spinelli, JJ, Kraft, P, Ennas, MG, Summerfield, G, Ferri, GM, Harris, RJ, Miligi, L, Pettitt, AR, North, KE, Allsup, DJ, Fraumeni, JF, Bailey, JR, Offit, K, Pratt, G, Hjalgrim, H, Pepper, C, Chanock, SJ, Fegan, C, Rosenquist, R, de Sanjose, S, Carracedo, A, Dyer, MJS, Catovsky, D, Campo, E, Cerhan, JR, Allan, JM, Rothman, N, Houlston, R, and Slager, SL

Abstract

Several chronic 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

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

Author

Bernatsky, S, Garcia, HAV, Spinelli, JJ, Gaffney, P, Smedby, KE, Ramsey-Goldman, R, Wang, SS, Adami, H-O, Albanes, D, Angelucci, E, Ansell, SM, Asmann, YW, Becker, N, Benavente, Y, Berndt, SI, Bertrand, KA, Birmann, BM, Boeing, H, Boffetta, P, Bracci, PM, Brennan, P, Brooks-Wilson, AR, Cerhan, JR, Chanock, SJ, Clavel, J, Conde, L, Cotenbader, KH, Cox, DG, Cozen, W, Crouch, S, De Roos, AJ, de Sanjose, S, Di Lollo, S, Diver, WR, Dogan, A, Foretova, L, Ghesquieres, H, Giles, GG, Glimelius, B, Habermann, TM, Haioun, C, Hartge, P, Hjalgrim, H, Holford, TR, Holly, EA, Jackson, RD, Kaaks, R, Kane, E, Kelly, RS, Klein, RJ, Kraft, P, Kricker, A, Lan, Q, Lawrence, C, Liebow, M, Lightfoot, T, Link, BK, Maynadie, M, Mckay, J, Melbye, M, Molina, TJ, Monnereau, A, Morton, LM, Nieters, A, North, KE, Novak, AJ, Offit, K, Purdue, MP, Rais, M, Riby, J, Roman, E, Rothman, N, Salles, G, Severi, G, Severson, RK, Skibola, CF, Slager, SL, Smith, A, Smith, MT, Southey, MC, Staines, A, Teras, LR, Thompson, CA, Tilly, H, Tinker, LF, Tjonneland, A, Turner, J, Vajdic, CM, Vermeulen, RCH, Vijai, J, Vineis, P, Virtamo, J, Wang, Z, Weinstein, S, Witzig, TE, Zelenetz, A, Zeleniuch-Jacquotte, A, Zhang, Y, Zheng, T, Zucca, M, Clarke, AE, Bernatsky, S, Garcia, HAV, Spinelli, JJ, Gaffney, P, Smedby, KE, Ramsey-Goldman, R, Wang, SS, Adami, H-O, Albanes, D, Angelucci, E, Ansell, SM, Asmann, YW, Becker, N, Benavente, Y, Berndt, SI, Bertrand, KA, Birmann, BM, Boeing, H, Boffetta, P, Bracci, PM, Brennan, P, Brooks-Wilson, AR, Cerhan, JR, Chanock, SJ, Clavel, J, Conde, L, Cotenbader, KH, Cox, DG, Cozen, W, Crouch, S, De Roos, AJ, de Sanjose, S, Di Lollo, S, Diver, WR, Dogan, A, Foretova, L, Ghesquieres, H, Giles, GG, Glimelius, B, Habermann, TM, Haioun, C, Hartge, P, Hjalgrim, H, Holford, TR, Holly, EA, Jackson, RD, Kaaks, R, Kane, E, Kelly, RS, Klein, RJ, Kraft, P, Kricker, A, Lan, Q, Lawrence, C, Liebow, M, Lightfoot, T, Link, BK, Maynadie, M, Mckay, J, Melbye, M, Molina, TJ, Monnereau, A, Morton, LM, Nieters, A, North, KE, Novak, AJ, Offit, K, Purdue, MP, Rais, M, Riby, J, Roman, E, Rothman, N, Salles, G, Severi, G, Severson, RK, Skibola, CF, Slager, SL, Smith, A, Smith, MT, Southey, MC, Staines, A, Teras, LR, Thompson, CA, Tilly, H, Tinker, LF, Tjonneland, A, Turner, J, Vajdic, CM, Vermeulen, RCH, Vijai, J, Vineis, P, Virtamo, J, Wang, Z, Weinstein, S, Witzig, TE, Zelenetz, A, Zeleniuch-Jacquotte, A, Zhang, Y, Zheng, T, Zucca, M, and Clarke, AE

Abstract

OBJECTIVE: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide 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.

Published
2017

10. GB VIRUS-C (GBV-C) INFECTION AND RISK OF LYMPHOMA: A CASE-CONTROL STUDY FROM NORTH AMERICA

Author

Fama, A., primary, Allmer, C., additional, Link, B.K., additional, Xiang, J., additional, Klinzman, D., additional, Feldman, A.J., additional, Nowakowski, G.S., additional, Liebow, M., additional, Larson, M.C., additional, Slager, S.L., additional, Call, T.G., additional, Habermann, T.M., additional, Cerhan, J.R., additional, and Stapleton, J.T., additional

Published
2017
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11. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

Author

Berndt, SI, Camp, NJ, Skibola, CF, Vijai, J, Wang, Z, Gu, J, Nieters, A, Kelly, RS, Smedby, KE, Monnereau, A, Cozen, W, Cox, A, Wang, SS, Lan, Q, Teras, LR, Machado, M, Yeager, M, Brooks-Wilson, AR, Hartge, P, Purdue, MP, Birmann, BM, Vajdic, CM, Cocco, P, Zhang, Y, Giles, GG, Zeleniuch-Jacquotte, A, Lawrence, C, Montalvan, R, Burdett, L, Hutchinson, A, Ye, Y, Call, TG, Shanafelt, TD, Novak, AJ, Kay, NE, Liebow, M, Cunningham, JM, Allmer, C, Hjalgrim, H, Adami, H-O, Melbye, M, Glimelius, B, Chang, ET, Glenn, M, Curtin, K, Cannon-Albright, LA, Diver, WR, Link, BK, Weiner, GJ, Conde, L, Bracci, PM, Riby, J, Arnett, DK, Zhi, D, Leach, JM, Holly, EA, Jackson, RD, Tinker, LF, Benavente, Y, Sala, N, Casabonne, D, Becker, N, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, McKay, J, Staines, A, Chaffee, KG, Achenbach, SJ, Vachon, CM, Goldin, LR, Strom, SS, Leis, JF, Weinberg, JB, Caporaso, NE, Norman, AD, De Roos, AJ, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Kaaks, R, Masala, G, Weiderpass, E, Chirlaque, M-D, Vermeulen, RCH, Travis, RC, Southey, MC, Milne, RL, Albanese, D, Virtamo, J, Weinstein, S, Clavel, J, Zheng, T, Holford, TR, Villano, DJ, Maria, A, Spinelli, JJ, Gascoyne, RD, Connors, JM, Bertrand, KA, Giovannucci, E, Kraft, P, Kricker, A, Turner, J, Ennas, MG, Ferri, GM, Miligi, L, Liang, L, Ma, B, Huang, J, Crouch, S, Park, J-H, Chatterjee, N, North, KE, Snowden, JA, Wright, J, Fraumeni, JF, Offit, K, Wu, X, de Sanjose, S, Cerhan, JR, Chanock, SJ, Rothman, N, Slager, SL, Berndt, SI, Camp, NJ, Skibola, CF, Vijai, J, Wang, Z, Gu, J, Nieters, A, Kelly, RS, Smedby, KE, Monnereau, A, Cozen, W, Cox, A, Wang, SS, Lan, Q, Teras, LR, Machado, M, Yeager, M, Brooks-Wilson, AR, Hartge, P, Purdue, MP, Birmann, BM, Vajdic, CM, Cocco, P, Zhang, Y, Giles, GG, Zeleniuch-Jacquotte, A, Lawrence, C, Montalvan, R, Burdett, L, Hutchinson, A, Ye, Y, Call, TG, Shanafelt, TD, Novak, AJ, Kay, NE, Liebow, M, Cunningham, JM, Allmer, C, Hjalgrim, H, Adami, H-O, Melbye, M, Glimelius, B, Chang, ET, Glenn, M, Curtin, K, Cannon-Albright, LA, Diver, WR, Link, BK, Weiner, GJ, Conde, L, Bracci, PM, Riby, J, Arnett, DK, Zhi, D, Leach, JM, Holly, EA, Jackson, RD, Tinker, LF, Benavente, Y, Sala, N, Casabonne, D, Becker, N, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, McKay, J, Staines, A, Chaffee, KG, Achenbach, SJ, Vachon, CM, Goldin, LR, Strom, SS, Leis, JF, Weinberg, JB, Caporaso, NE, Norman, AD, De Roos, AJ, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Kaaks, R, Masala, G, Weiderpass, E, Chirlaque, M-D, Vermeulen, RCH, Travis, RC, Southey, MC, Milne, RL, Albanese, D, Virtamo, J, Weinstein, S, Clavel, J, Zheng, T, Holford, TR, Villano, DJ, Maria, A, Spinelli, JJ, Gascoyne, RD, Connors, JM, Bertrand, KA, Giovannucci, E, Kraft, P, Kricker, A, Turner, J, Ennas, MG, Ferri, GM, Miligi, L, Liang, L, Ma, B, Huang, J, Crouch, S, Park, J-H, Chatterjee, N, North, KE, Snowden, JA, Wright, J, Fraumeni, JF, Offit, K, Wu, X, de Sanjose, S, Cerhan, JR, Chanock, SJ, Rothman, N, and Slager, SL

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<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

Published
2016

12. A genome-wide association study of marginal zone lymphoma shows association to the HLA region

Author

Vijai, J, Wang, Z, Berndt, SI, Skibola, CF, Slager, SL, de Sanjose, S, Melbye, M, Glimelius, B, Bracci, PM, Conde, L, Birmann, BM, Wang, SS, Brooks-Wilson, AR, Lan, Q, de Bakker, PIW, Vermeulen, RCH, Portlock, C, Ansell, SM, Link, BK, Riby, J, North, KE, Gu, J, Hjalgrim, H, Cozen, W, Becker, N, Teras, LR, Spinelli, JJ, Turner, J, Zhang, Y, Purdue, MP, Giles, GG, Kelly, RS, Zeleniuch-Jacquotte, A, Ennas, MG, Monnereau, A, Bertrand, KA, Albanes, D, Lightfoot, T, Yeager, M, Chung, CC, Burdett, L, Hutchinson, A, Lawrence, C, Montalvan, R, Liang, L, Huang, J, Ma, B, Villano, DJ, Maria, A, Corines, M, Thomas, T, Novak, AJ, Dogan, A, Liebow, M, Thompson, CA, Witzig, TE, Habermann, TM, Weiner, GJ, Smith, MT, Holly, EA, Jackson, RD, Tinker, LF, Ye, Y, Adami, H-O, Smedby, KE, De Roos, AJ, Hartge, P, Morton, LM, Severson, RK, Benavente, Y, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, Mckay, J, Staines, A, Diver, WR, Vajdic, CM, Armstrong, BK, Kricker, A, Zheng, T, Holford, TR, Severi, G, Vineis, P, Ferri, GM, Ricco, R, Miligi, L, Clavel, J, Giovannucci, E, Kraft, P, Virtamo, J, Smith, A, Kane, E, Roman, E, Chiu, BCH, Fraumeni, JF, Wu, X, Cerhan, JR, Offit, K, Chanock, SJ, Rothman, N, Nieters, A, Vijai, J, Wang, Z, Berndt, SI, Skibola, CF, Slager, SL, de Sanjose, S, Melbye, M, Glimelius, B, Bracci, PM, Conde, L, Birmann, BM, Wang, SS, Brooks-Wilson, AR, Lan, Q, de Bakker, PIW, Vermeulen, RCH, Portlock, C, Ansell, SM, Link, BK, Riby, J, North, KE, Gu, J, Hjalgrim, H, Cozen, W, Becker, N, Teras, LR, Spinelli, JJ, Turner, J, Zhang, Y, Purdue, MP, Giles, GG, Kelly, RS, Zeleniuch-Jacquotte, A, Ennas, MG, Monnereau, A, Bertrand, KA, Albanes, D, Lightfoot, T, Yeager, M, Chung, CC, Burdett, L, Hutchinson, A, Lawrence, C, Montalvan, R, Liang, L, Huang, J, Ma, B, Villano, DJ, Maria, A, Corines, M, Thomas, T, Novak, AJ, Dogan, A, Liebow, M, Thompson, CA, Witzig, TE, Habermann, TM, Weiner, GJ, Smith, MT, Holly, EA, Jackson, RD, Tinker, LF, Ye, Y, Adami, H-O, Smedby, KE, De Roos, AJ, Hartge, P, Morton, LM, Severson, RK, Benavente, Y, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, Mckay, J, Staines, A, Diver, WR, Vajdic, CM, Armstrong, BK, Kricker, A, Zheng, T, Holford, TR, Severi, G, Vineis, P, Ferri, GM, Ricco, R, Miligi, L, Clavel, J, Giovannucci, E, Kraft, P, Virtamo, J, Smith, A, Kane, E, Roman, E, Chiu, BCH, Fraumeni, JF, Wu, X, Cerhan, JR, Offit, K, Chanock, SJ, Rothman, N, and Nieters, A

Abstract

Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.

Published
2015

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

Author

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., Jr, F.J.F., de Sanjose, S., Hjalgrim, H., Cerhan, J.R., Chanock, S.J., Rothman, N., and Slager, S.L.

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.

Published
2013

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

Author

Cerhan, JR, Berndt, SI, Vijai, J, Ghesquieres, H, McKay, J, Wang, SS, Wang, Z, Yeager, M, Conde, L, de Bakker, PIW, Nieters, A, Cox, D, Burdett, L, Monnereau, A, Flowers, CR, De Roos, AJ, Brooks-Wilson, AR, Lan, Q, Severi, G, Melbye, M, Gu, J, Jackson, RD, Kane, E, Teras, LR, Purdue, MP, Vajdic, CM, Spinelli, JJ, Giles, GG, Albanes, D, Kelly, RS, Zucca, M, Bertrand, KA, Zeleniuch-Jacquotte, A, Lawrence, C, Hutchinson, A, Zhi, D, Habermann, TM, Link, BK, Novak, AJ, Dogan, A, Asmann, YW, Liebow, M, Thompson, CA, Ansell, SM, Witzig, TE, Weiner, GJ, Veron, AS, Zelenika, D, Tilly, H, Haioun, C, Molina, TJ, Hjalgrim, H, Glimelius, B, Adami, H-O, Bracci, PM, Riby, J, Smith, MT, Holly, EA, Cozen, W, Hartge, P, Morton, LM, Severson, RK, Tinker, LF, North, KE, Becker, N, Benavente, Y, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, Staines, A, Lightfoot, T, Crouch, S, Smith, A, Roman, E, Diver, WR, Offit, K, Zelenetz, A, Klein, RJ, Villano, DJ, Zheng, T, Zhang, Y, Holford, TR, Kricker, A, Turner, J, Southey, MC, Clavel, J, Virtamo, J, Weinstein, S, Riboli, E, Vineis, P, Kaaks, R, Trichopoulos, D, Vermeulen, RCH, Boeing, H, Tjonneland, A, Angelucci, E, Di Lollo, S, Rais, M, Birmann, BM, Laden, F, Giovannucci, E, Kraft, P, Huang, J, Ma, B, Ye, Y, Chiu, BCH, Sampson, J, Liang, L, Park, J-H, Chung, CC, Weisenburger, DD, Chatterjee, N, Fraumeni, JF, Slager, SL, Wu, X, de Sanjose, S, Smedby, KE, Salles, G, Skibola, CF, Rothman, N, Chanock, SJ, Cerhan, JR, Berndt, SI, Vijai, J, Ghesquieres, H, McKay, J, Wang, SS, Wang, Z, Yeager, M, Conde, L, de Bakker, PIW, Nieters, A, Cox, D, Burdett, L, Monnereau, A, Flowers, CR, De Roos, AJ, Brooks-Wilson, AR, Lan, Q, Severi, G, Melbye, M, Gu, J, Jackson, RD, Kane, E, Teras, LR, Purdue, MP, Vajdic, CM, Spinelli, JJ, Giles, GG, Albanes, D, Kelly, RS, Zucca, M, Bertrand, KA, Zeleniuch-Jacquotte, A, Lawrence, C, Hutchinson, A, Zhi, D, Habermann, TM, Link, BK, Novak, AJ, Dogan, A, Asmann, YW, Liebow, M, Thompson, CA, Ansell, SM, Witzig, TE, Weiner, GJ, Veron, AS, Zelenika, D, Tilly, H, Haioun, C, Molina, TJ, Hjalgrim, H, Glimelius, B, Adami, H-O, Bracci, PM, Riby, J, Smith, MT, Holly, EA, Cozen, W, Hartge, P, Morton, LM, Severson, RK, Tinker, LF, North, KE, Becker, N, Benavente, Y, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, Staines, A, Lightfoot, T, Crouch, S, Smith, A, Roman, E, Diver, WR, Offit, K, Zelenetz, A, Klein, RJ, Villano, DJ, Zheng, T, Zhang, Y, Holford, TR, Kricker, A, Turner, J, Southey, MC, Clavel, J, Virtamo, J, Weinstein, S, Riboli, E, Vineis, P, Kaaks, R, Trichopoulos, D, Vermeulen, RCH, Boeing, H, Tjonneland, A, Angelucci, E, Di Lollo, S, Rais, M, Birmann, BM, Laden, F, Giovannucci, E, Kraft, P, Huang, J, Ma, B, Ye, Y, Chiu, BCH, Sampson, J, Liang, L, Park, J-H, Chung, CC, Weisenburger, DD, Chatterjee, N, Fraumeni, JF, Slager, SL, Wu, X, de Sanjose, S, Smedby, KE, Salles, G, Skibola, CF, Rothman, N, and Chanock, SJ

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.

Published
2014

15. Etiologic Heterogeneity Among Non-Hodgkin Lymphoma Subtypes: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

Author

Morton, L. M., primary, Slager, S. L., additional, Cerhan, J. R., additional, Wang, S. S., additional, Vajdic, C. M., additional, Skibola, C. F., additional, Bracci, P. M., additional, de Sanjose, S., additional, Smedby, K. E., additional, Chiu, B. C. H., additional, Zhang, Y., additional, Mbulaiteye, S. M., additional, Monnereau, A., additional, Turner, J. J., additional, Clavel, J., additional, Adami, H.-O., additional, Chang, E. T., additional, Glimelius, B., additional, Hjalgrim, H., additional, Melbye, M., additional, Crosignani, P., additional, di Lollo, S., additional, Miligi, L., additional, Nanni, O., additional, Ramazzotti, V., additional, Rodella, S., additional, Costantini, A. S., additional, Stagnaro, E., additional, Tumino, R., additional, Vindigni, C., additional, Vineis, P., additional, Becker, N., additional, Benavente, Y., additional, Boffetta, P., additional, Brennan, P., additional, Cocco, P., additional, Foretova, L., additional, Maynadie, M., additional, Nieters, A., additional, Staines, A., additional, Colt, J. S., additional, Cozen, W., additional, Davis, S., additional, de Roos, A. J., additional, Hartge, P., additional, Rothman, N., additional, Severson, R. K., additional, Holly, E. A., additional, Call, T. G., additional, Feldman, A. L., additional, Habermann, T. M., additional, Liebow, M., additional, Blair, A., additional, Cantor, K. P., additional, Kane, E. V., additional, Lightfoot, T., additional, Roman, E., additional, Smith, A., additional, Brooks-Wilson, A., additional, Connors, J. M., additional, Gascoyne, R. D., additional, Spinelli, J. J., additional, Armstrong, B. K., additional, Kricker, A., additional, Holford, T. R., additional, Lan, Q., additional, Zheng, T., additional, Orsi, L., additional, Dal Maso, L., additional, Franceschi, S., additional, La Vecchia, C., additional, Negri, E., additional, Serraino, D., additional, Bernstein, L., additional, Levine, A., additional, Friedberg, J. W., additional, Kelly, J. L., additional, Berndt, S. I., additional, Birmann, B. M., additional, Clarke, C. A., additional, Flowers, C. R., additional, Foran, J. M., additional, Kadin, M. E., additional, Paltiel, O., additional, Weisenburger, D. D., additional, Linet, M. S., additional, and Sampson, J. N., additional

Published
2014
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16. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Author

Berndt, SI, Skibola, CF, Joseph, V, Camp, NJ, Nieters, A, Wang, Z, Cozen, W, Monnereau, A, Wang, SS, Kelly, RS, Lan, Q, Teras, LR, Chatterjee, N, Chung, CC, Yeager, M, Brooks-Wilson, AR, Hartge, P, Purdue, MP, Birmann, BM, Armstrong, BK, Cocco, P, Zhang, Y, Severi, G, Zeleniuch-Jacquotte, A, Lawrence, C, Burdette, L, Yuenger, J, Hutchinson, A, Jacobs, KB, Call, TG, Shanafelt, TD, Novak, AJ, Kay, NE, Liebow, M, Wang, AH, Smedby, KE, Adami, H-O, Melbye, M, Glimelius, B, Chang, ET, Glenn, M, Curtin, K, Cannon-Albright, LA, Jones, B, Diver, WR, Link, BK, Weiner, GJ, Conde, L, Bracci, PM, Riby, J, Holly, EA, Smith, MT, Jackson, RD, Tinker, LF, Benavente, Y, Becker, N, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, McKay, J, Staines, A, Rabe, KG, Achenbach, SJ, Vachon, CM, Goldin, LR, Strom, SS, Lanasa, MC, Spector, LG, Leis, JF, Cunningham, JM, Weinberg, JB, Morrison, VA, Caporaso, NE, Norman, AD, Linet, MS, De Roos, AJ, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Kaaks, R, Trichopoulos, D, Masala, G, Weiderpass, E, Chirlaque, M-D, Vermeulen, RCH, Travis, RC, Giles, GG, Albanes, D, Virtamo, J, Weinstein, S, Clavel, J, Zheng, T, Holford, TR, Offit, K, Zelenetz, A, Klein, RJ, Spinelli, JJ, Bertrand, KA, Laden, F, Giovannucci, E, Kraft, P, Kricker, A, Turner, J, Vajdic, CM, Ennas, MG, Ferri, GM, Miligi, L, Liang, L, Sampson, J, Crouch, S, Park, J-H, North, KE, Cox, A, Snowden, JA, Wright, J, Carracedo, A, Lopez-Otin, C, Bea, S, Salaverria, I, Martin-Garcia, D, Campo, E, Fraumeni, JF, de Sanjose, S, Hjalgrim, H, Cerhan, JR, Chanock, SJ, Rothman, N, Slager, SL, Berndt, SI, Skibola, CF, Joseph, V, Camp, NJ, Nieters, A, Wang, Z, Cozen, W, Monnereau, A, Wang, SS, Kelly, RS, Lan, Q, Teras, LR, Chatterjee, N, Chung, CC, Yeager, M, Brooks-Wilson, AR, Hartge, P, Purdue, MP, Birmann, BM, Armstrong, BK, Cocco, P, Zhang, Y, Severi, G, Zeleniuch-Jacquotte, A, Lawrence, C, Burdette, L, Yuenger, J, Hutchinson, A, Jacobs, KB, Call, TG, Shanafelt, TD, Novak, AJ, Kay, NE, Liebow, M, Wang, AH, Smedby, KE, Adami, H-O, Melbye, M, Glimelius, B, Chang, ET, Glenn, M, Curtin, K, Cannon-Albright, LA, Jones, B, Diver, WR, Link, BK, Weiner, GJ, Conde, L, Bracci, PM, Riby, J, Holly, EA, Smith, MT, Jackson, RD, Tinker, LF, Benavente, Y, Becker, N, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, McKay, J, Staines, A, Rabe, KG, Achenbach, SJ, Vachon, CM, Goldin, LR, Strom, SS, Lanasa, MC, Spector, LG, Leis, JF, Cunningham, JM, Weinberg, JB, Morrison, VA, Caporaso, NE, Norman, AD, Linet, MS, De Roos, AJ, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Kaaks, R, Trichopoulos, D, Masala, G, Weiderpass, E, Chirlaque, M-D, Vermeulen, RCH, Travis, RC, Giles, GG, Albanes, D, Virtamo, J, Weinstein, S, Clavel, J, Zheng, T, Holford, TR, Offit, K, Zelenetz, A, Klein, RJ, Spinelli, JJ, Bertrand, KA, Laden, F, Giovannucci, E, Kraft, P, Kricker, A, Turner, J, Vajdic, CM, Ennas, MG, Ferri, GM, Miligi, L, Liang, L, Sampson, J, Crouch, S, Park, J-H, North, KE, Cox, A, Snowden, JA, Wright, J, Carracedo, A, Lopez-Otin, C, Bea, S, Salaverria, I, Martin-Garcia, D, Campo, E, Fraumeni, JF, de Sanjose, S, Hjalgrim, H, Cerhan, JR, Chanock, SJ, Rothman, N, and Slager, SL

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.

Published
2013

17. Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis

Author

Cunningham, J M, Vierkant, R A, Sellers, T A, Phelan, C, Rider, D N, Liebow, M, Schildkraut, J, Berchuck, A, Couch, F J, Wang, X, Fridley, B L, Gentry-Maharaj, A, Menon, U, Hogdall, E, Kjær, Susanne Krüger, Whittemore, A, DiCioccio, R, Song, H, Gayther, S A, Ramus, S J, Pharaoh, P D P, Goode, E L, Cunningham, J M, Vierkant, R A, Sellers, T A, Phelan, C, Rider, D N, Liebow, M, Schildkraut, J, Berchuck, A, Couch, F J, Wang, X, Fridley, B L, Gentry-Maharaj, A, Menon, U, Hogdall, E, Kjær, Susanne Krüger, Whittemore, A, DiCioccio, R, Song, H, Gayther, S A, Ramus, S J, Pharaoh, P D P, and Goode, E L

Abstract

Udgivelsesdato: 2009-Oct-20, BACKGROUND: Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide. METHODS: We examined single nucleotide polymorphisms (SNPs) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) were genotyped using an Illumina assay. RESULTS: Eleven variants in nine genes (ABL1, CCNB2, CDKN1A, CCND3, E2F2, CDK2, E2F3, CDC2, and CDK7) were associated with risk of ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population [odds ratio, OR(BB vs AA) 2.81 (1.29-6.09), P=0.01] was also observed in a replication population, and the association remained suggestive in the combined analysis [OR(BB vs AA) 1.59 (1.08-2.34), P=0.02]. No other SNP associations remained suggestive in the replication populations. CONCLUSION: ABL1 has been implicated in multiple processes including cell division, cell adhesion and cellular stress response. These results suggest that characterization of the function of genetic variation in this gene in other ovarian cancer populations is warranted.

Published
2009

18. Consortium analysis of 7 candidate SNPs for ovarian cancer.

Author

Harrap K., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Papadimos D., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Purdie D., Whiteman D., Zeps N., Jobling T., Tran H., Ramus S.J., Vierkant R.A., Johnatty S.E., Pike M.C., Van Den Berg D.J., Wu A.H., Pearce C.L., Menon U., Gentry-Maharaj A., Gayther S.A., DiCioccio R.A., McGuire V., Whittemore A.S., Song H., Easton D.F., Pharoah P.D.P., Garcia-Closas M., Chanock S., Lissowska J., Brinton L., Terry K.L., Cramer D.W., Tworoger S.S., Hankinson S.E., Berchuck A., Moorman P.G., Schildkraut J.M., Cunningham J.M., Liebow M., Kjaer S.K., Hogdall E., Hogdall C., Blaakaer J., Ness R.B., Moysich K.B., Edwards R.P., Carney M.E., Lurie G., Goodman M.T., Wang-Gohrke S., Kropp S., Chang-Claude J., Webb P., Chen X., Beesley J., Chenevix-Trench G., Goode E.L., Bowtell D., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes V.L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Proietto A., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Harrap K., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Papadimos D., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Purdie D., Whiteman D., Zeps N., Jobling T., Tran H., Ramus S.J., Vierkant R.A., Johnatty S.E., Pike M.C., Van Den Berg D.J., Wu A.H., Pearce C.L., Menon U., Gentry-Maharaj A., Gayther S.A., DiCioccio R.A., McGuire V., Whittemore A.S., Song H., Easton D.F., Pharoah P.D.P., Garcia-Closas M., Chanock S., Lissowska J., Brinton L., Terry K.L., Cramer D.W., Tworoger S.S., Hankinson S.E., Berchuck A., Moorman P.G., Schildkraut J.M., Cunningham J.M., Liebow M., Kjaer S.K., Hogdall E., Hogdall C., Blaakaer J., Ness R.B., Moysich K.B., Edwards R.P., Carney M.E., Lurie G., Goodman M.T., Wang-Gohrke S., Kropp S., Chang-Claude J., Webb P., Chen X., Beesley J., Chenevix-Trench G., Goode E.L., Bowtell D., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes V.L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Proietto A., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., and Gard G.

Abstract

The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach. © 2008 Wiley-Liss, Inc.

Published
2008

19. Consortium analysis of 7 candidate SNPs for ovarian cancer

Author

Ramus, S.J., Vierkant, R.A., Johnatty, S.E., Pike, M.C., Berg, D.J. Van Den, Wu, A.H., Pearce, C.L., Menon, U., Gentry-Maharaj, A., Gayther, S.A., DiCioccio, R.A., McGuire, V., Whittemore, A.S., Song, H., Easton, D.F., Pharoah, P.D., Garcia-Closas, M., Chanock, S., Lissowska, J., Brinton, L., Terry, K.L., Cramer, D.W., Tworoger, S.S., Hankinson, S.E., Berchuck, A., Moorman, P.G., Schildkraut, J.M., Cunningham, J.M., Liebow, M., Kjaer, S.K., Hogdall, C., Blaakaer, J., Ness, R.B., Moysich, K.B., Edwards, R.P., Carney, M.E., Lurie, G., Goodman, M.T., Wang-Gohrke, S., Kropp, S., Chang-Claude, J., Webb, P.M., Chen, X., Beesley, J., Chenevix-Trench, G., Goode, E.L., Høgdall, Estrid Vilma Solyom, Ramus, S.J., Vierkant, R.A., Johnatty, S.E., Pike, M.C., Berg, D.J. Van Den, Wu, A.H., Pearce, C.L., Menon, U., Gentry-Maharaj, A., Gayther, S.A., DiCioccio, R.A., McGuire, V., Whittemore, A.S., Song, H., Easton, D.F., Pharoah, P.D., Garcia-Closas, M., Chanock, S., Lissowska, J., Brinton, L., Terry, K.L., Cramer, D.W., Tworoger, S.S., Hankinson, S.E., Berchuck, A., Moorman, P.G., Schildkraut, J.M., Cunningham, J.M., Liebow, M., Kjaer, S.K., Hogdall, C., Blaakaer, J., Ness, R.B., Moysich, K.B., Edwards, R.P., Carney, M.E., Lurie, G., Goodman, M.T., Wang-Gohrke, S., Kropp, S., Chang-Claude, J., Webb, P.M., Chen, X., Beesley, J., Chenevix-Trench, G., Goode, E.L., and Høgdall, Estrid Vilma Solyom

Abstract

The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach Udgivelsesdato: 2008/7/15

Published
2008

20. Single-nucleotide polymorphism rs1052501 associated with monoclonal gammopathy of undetermined significance and multiple myeloma

Author

Greenberg, A J, primary, Lee, A M, additional, Serie, D J, additional, McDonnell, S K, additional, Cerhan, J R, additional, Liebow, M, additional, Larson, D R, additional, Colby, C L, additional, Norman, A D, additional, Kyle, R A, additional, Kumar, S, additional, Rajkumar, S V, additional, Diasio, R B, additional, Slager, S L, additional, and Vachon, C M, additional

Published
2012
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21. The introduction of a diagnostic decision support system (DXplain™) into the workflow of a teaching hospital service can decrease the cost of service for diagnostically challenging Diagnostic Related Groups (DRGs).

Author

Elkin PL, Liebow M, Bauer BA, Chaliki S, Wahner-Roedler D, Bundrick J, Lee M, Brown SH, Froehling D, Bailey K, Famiglietti K, Kim R, Hoffer E, Feldman M, Barnett GO, Elkin, Peter L, Liebow, Mark, Bauer, Brent A, Chaliki, Swarna, and Wahner-Roedler, Dietlind

Abstract

Background: In an era of short inpatient stays, residents may overlook relevant elements of the differential diagnosis as they try to evaluate and treat patients. However, if a resident's first principal diagnosis is wrong, the patient's appropriate evaluation and treatment may take longer, cost more, and lead to worse outcomes. A diagnostic decision support system may lead to the generation of a broader differential diagnosis that more often includes the correct diagnosis, permitting a shorter, more effective, and less costly hospital stay.Methods: We provided residents on General Medicine services access to DXplain, an established computer-based diagnostic decision support system, for 6 months. We compared charges and cost of service for diagnostically challenging cases seen during the fourth through sixth month of access to DXplain (intervention period) to control cases seen in the 6 months before the system was made available.Results: 564 cases were identified as diagnostically challenging by our criteria during the intervention period along with 1173 cases during the control period. Total charges were $1281 lower (p=.006), Medicare Part A charges $1032 lower (p=0.006) and cost of service $990 lower (p=0.001) per admission in the intervention cases than in control cases.Conclusions: Using DXplain on all diagnostically challenging cases might save our medical center over $2,000,000 a year on the General Medicine Services alone. Using clinical diagnostic decision support systems may improve quality and decrease cost substantially at teaching hospitals. [ABSTRACT FROM AUTHOR]

Published
2010
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22. Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis.

Author

Cunningham, J. M., Vierkant, R. A., Sellers, T. A., Phelan, C., Rider, D. N., Liebow, M., Schildkraut, J., Berchuck, A., Couch, F. J., Wang, X., Fridley, B. L., Gentry-Maharaj, A., Menon, U., Hogdall, E., Kjaer, S., Whittemore, A., DiCioccio, R., Song, H., Gayther, S. A., and Ramus, S. J.

Subjects
NUCLEOTIDES, GENETIC polymorphisms, GENES, CELL cycle regulation, OVARIAN cancer, CYCLINS, CYCLIN-dependent kinases, CELL cycle, DISEASE susceptibility, OVARIAN tumors, RESEARCH funding, TRANSFERASES
Abstract

Background: Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide.Methods: We examined single nucleotide polymorphisms (SNPs) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) were genotyped using an Illumina assay.Results: Eleven variants in nine genes (ABL1, CCNB2, CDKN1A, CCND3, E2F2, CDK2, E2F3, CDC2, and CDK7) were associated with risk of ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population [odds ratio, OR(BB vs AA) 2.81 (1.29-6.09), P=0.01] was also observed in a replication population, and the association remained suggestive in the combined analysis [OR(BB vs AA) 1.59 (1.08-2.34), P=0.02]. No other SNP associations remained suggestive in the replication populations.Conclusion: ABL1 has been implicated in multiple processes including cell division, cell adhesion and cellular stress response. These results suggest that characterization of the function of genetic variation in this gene in other ovarian cancer populations is warranted. [ABSTRACT FROM AUTHOR]

Published
2009
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24. Achieving a high-performance health care system with universal access: what the United States can learn from other countries.

Author

Ginsburg JA, Doherty RB, Ralston JF Jr., Senkeeto N, Cooke M, Cutler C, Fleming DA, Freeman BP, Gluckman RA, Liebow M, McLean RM, Musana KA, Nichols PM, Purtle MW, Reynolds PP, Weaver KM, Dale DC, Levine JS, Stubbs JW, and American College of Physicians

Abstract

This position paper concerns improving health care in the United States. Unlike previous highly focused policy papers by the American College of Physicians, this article takes a comprehensive approach to improving access, quality, and efficiency of care. The first part describes health care in the United States. The second compares it with health care in other countries. The concluding section proposes lessons that the United States can learn from these countries and recommendations for achieving a high-performance health care system in the United States. The articles are based on a position paper developed by the American College of Physicians' Health and Public Policy Committee. This policy paper (not included in this article) also provides a detailed analysis of health care systems in 12 other industrialized countries. Although we can learn much from other health systems, the College recognizes that our political and social culture, demographics, and form of government will shape any solution for the United States. This caution notwithstanding, we have identified several approaches that have worked well for countries like ours and could probably be adapted to the unique circumstances in the United States. [ABSTRACT FROM AUTHOR]

Published
2008

25. The world we live in: health policy from a primary care perspective.

Author

Liebow, Mark, Bierman, Arlene S., Fein, Oliver, Liebow, M, Bierman, A S, and Fein, O

Subjects
HEALTH policy, PRIMARY care
Abstract

Federal, state, and local health policies shape the landscape on which clinical decisions are made, sometimes in ways that are not apparent when those policies are formulated.[sup 1,2] Whether the decisions are about insurance coverage and benefits, payment models for care and resource allocation, health workforce issues, or mechanisms to improve health care quality, these policies affect what we do in clinical care, research, and education. Solutions to the myriad challenges that confront us and our patients daily often seem elusive. Discussion about these issues can become contentious, and sometimes appears to be driven by emotion rather than reason. In an ideal world these difficult decisions would be informed by evidence. The impact of new policies on access to, cost, quality, and outcomes of care would be formally evaluated. Critical examinations of the scientific basis for policy, empirical analyses of the impact of policies, and syntheses of the evidence underpinning policy challenges can be helpful to JGIM readers who want to understand how the health care system works. In this issue of JGIM, we introduce a new section entitled Health Policy, which will feature original policy-relevant research, scholarly reviews, and perspectives on health policy issues. Articles should place these issues in the context of their impact on practices, providers, patients, and populations. Articles that examine how alternative strategies foster or impede the delivery of high-quality primary care would be of special interest. We believe this section will fill a need for an outlet for articles that approach these issues from a primary care perspective and build on prior contributions of SGIM members in this area. [ABSTRACT FROM AUTHOR]

Published
2000
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26. Polymorphisms in NF-κB Inhibitors and Risk of Epithelial Ovarian Cancer

Author

Kelemen Linda E, Cunningham Julie M, Schildkraut Joellen M, Knutson Keith L, Anderson Stephanie, Fridley Brooke L, Phelan Catherine M, Vierkant Robert A, White Kristin L, Pankratz V Shane, Rider David N, Liebow Mark, Hartmann Lynn C, Sellers Thomas A, and Goode Ellen L

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The nuclear factor-κB (NF-κB) family is a set of transcription factors with key roles in the induction of the inflammatory response and may be the link between inflammation and cancer development. This pathway has been shown to influence ovarian epithelial tissue repair. Inhibitors of κB (IκB) prevent NF-κB activation by sequestering NF-κB proteins in the cytoplasm until IκB proteins are phosphorylated and degraded. Methods We used a case-control study to evaluate the association between single nucleotide polymorphisms (SNPs) in NFKBIA and NFKBIB (the genes encoding IκBα and IκBβ, respectively) and risk of epithelial ovarian cancer. We queried 19 tagSNPs and putative-functional SNPs among 930 epithelial ovarian cancer cases and 1,037 controls from two studies. Results The minor allele for one synonymous SNP in NFKBIA, rs1957106, was associated with decreased risk (p = 0.03). Conclusion Considering the number of single-SNP tests performed and null gene-level results, we conclude that NFKBIA and NFKBIB are not likely to harbor ovarian cancer risk alleles. Due to its biological significance in ovarian cancer, additional genes encoding NF-κB subunits, activating and inhibiting molecules, and signaling molecules warrant interrogation.

Published
2009
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27. Polymorphisms in NF-kappaB inhibitors and risk of epithelial ovarian cancer.

Author

White KL, Vierkant RA, Phelan CM, Fridley BL, Anderson S, Knutson KL, Schildkraut JM, Cunningham JM, Kelemen LE, Pankratz VS, Rider DN, Liebow M, Hartmann LC, Sellers TA, Goode EL, White, Kristin L, Vierkant, Robert A, Phelan, Catherine M, Fridley, Brooke L, and Anderson, Stephanie

Abstract

Background: The nuclear factor-kappaB (NF-kappaB) family is a set of transcription factors with key roles in the induction of the inflammatory response and may be the link between inflammation and cancer development. This pathway has been shown to influence ovarian epithelial tissue repair. Inhibitors of kappaB (IkappaB) prevent NF-kappaB activation by sequestering NF-kappaB proteins in the cytoplasm until IkappaB proteins are phosphorylated and degraded.Methods: We used a case-control study to evaluate the association between single nucleotide polymorphisms (SNPs) in NFKBIA and NFKBIB (the genes encoding IkappaBalpha and IkappaBbeta, respectively) and risk of epithelial ovarian cancer. We queried 19 tagSNPs and putative-functional SNPs among 930 epithelial ovarian cancer cases and 1,037 controls from two studies.Results: The minor allele for one synonymous SNP in NFKBIA, rs1957106, was associated with decreased risk (p = 0.03).Conclusion: Considering the number of single-SNP tests performed and null gene-level results, we conclude that NFKBIA and NFKBIB are not likely to harbor ovarian cancer risk alleles. Due to its biological significance in ovarian cancer, additional genes encoding NF-kappaB subunits, activating and inhibiting molecules, and signaling molecules warrant interrogation. [ABSTRACT FROM AUTHOR]

Published
2009
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28. 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

29. 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

30. 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

31. 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

32. Etiologic Heterogeneity Among Non-Hodgkin Lymphoma Subtypes: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

Author

Paige M. Bracci, Thomas M. Habermann, Kenneth P. Cantor, Stefania Rodella, John J. Spinelli, Brenda M. Birmann, Paul Brennan, Alain Monnereau, Christina A. Clarke, Eva Negri, Susan L. Slager, Elizabeth A. Holly, Patricia Hartge, Silvia Franceschi, Sonja I. Berndt, Silvia de Sanjosé, Paolo Vineis, Qing Lan, Anneclaire J. De Roos, Paolo Crosignani, Jennifer Turner, Randy D. Gascoyne, Joanne S. Colt, Eve Roman, Richard K. Severson, Alexandra M. Levine, Emanuele Stagnaro, Bengt Glimelius, Marc Maynadié, Jonathan W. Friedberg, Yawei Zhang, Theodore R. Holford, Angela Brooks-Wilson, Oriana Nanni, Dennis D. Weisenburger, Joshua N. Sampson, Nathaniel Rothman, Yolanda Benavente, Andrew L. Feldman, Leslie Bernstein, Pierluigi Cocco, Marshall E. Kadin, Luigino Dal Maso, Valerio Ramazzotti, Lenka Foretova, Lucia Miligi, Sophia S. Wang, Rosario Tumino, Hans-Olov Adami, Wendy Cozen, Tracy Lightfoot, Sam M. Mbulaiteye, Jacqueline Clavel, Tongzhang Zheng, Paolo Boffetta, Anne Kricker, Martha S. Linet, Alexandra Nieters, Christine F. Skibola, Claire M. Vajdic, Nikolaus Becker, Laurent Orsi, Eleanor Kane, Diego Serraino, Carlo La Vecchia, Alex Smith, James M. Foran, Lindsay M. Morton, Anthony Staines, Simonetta Di Lollo, Mads Melbye, Jennifer L. Kelly, James R. Cerhan, Timothy G. Call, Henrik Hjalgrim, Christopher R. Flowers, Bruce K. Armstrong, Joseph M. Connors, Mark Liebow, Ora Paltiel, Ellen T. Chang, Aaron Blair, Karin E. Smedby, Carla Vindigni, Brian C.-H. Chiu, Adele Seniori Costantini, Scott Davis, Morton, L.M., Slager, S.L., Cerhan, J.R., Wang, S.S., Vajdic, C.M., Skibola, C.F., Bracci, P.M., de Sanjosé, S., Smedby, K.E., Chiu, B.C.H., Zhang, Y., Mbulaiteye, S.M., Monnereau, A., Turner, J.J., Clavel, J., Adami, H.-O., Chang, E.T., Glimelius, B., Hjalgrim, H., Melbye, M., Crosignani, P., di Lollo, S., Miligi, L., Nanni, O., Ramazzotti, V., Rodella, S., Costantini, A.S., Stagnaro, E., Tumino, R., Vindigni, C., Vineis, P., Becker, N., Benavente, Y., Boffetta, P., Brennan, P., Cocco, P., Foretova, L., Maynadié, M., Nieters, A., Staines, A., Colt, J.S., Cozen, W., Davis, S., de Roos, A.J., Hartge, P., Rothman, N., Severson, R.K., Holly, E.A., Call, T.G., Feldman, A.L., Habermann, T.M., Liebow, M., Blair, A., Cantor, K.P., Kane, E.V., Lightfoot, T., Roman, E., Smith, A., Brooks-Wilson, A., Connors, J.M., Gascoyne, R.D., Spinelli, J.J., Armstrong, B.K., Kricker, A., Holford, T.R., Lan, Q., Zheng, T., Orsi, L., Dal Maso, L., Franceschi, S., La Vecchia, C., Negri, E., Serraino, D., Bernstein, L., Levine, A., Friedberg, J.W., Kelly, J.L., Berndt, S.I., Birmann, B.M., Clarke, C.A., Flowers, C.R., Foran, J.M., Kadin, M.E., Paltiel, O., Weisenburger, D.D., Linet, M.S., and Sampson, J.N.

Subjects
Adult, Male, Cancer Research, Adolescent, Chronic lymphocytic leukemia, Follicular lymphoma, Comorbidity, Disease, Non-Hodgkin lymphoma (NHL), Article, Young Adult, Risk Factors, immune system diseases, Occupational Exposure, hemic and lymphatic diseases, Odds Ratio, medicine, Cluster Analysis, Humans, Risk factor, Family history, Life Style, Aged, Aged, 80 and over, International Lymphoma Epidemiology Consortium (InterLymph), business.industry, Lymphoma, Non-Hodgkin, Australia, Case-control study, General Medicine, Odds ratio, Middle Aged, medicine.disease, Lymphoma, Europe, Oncology, Case-Control Studies, North America, Immunology, Female, business
Abstract

Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy and the fifth most common type of cancer in more developed regions of the world (1). Numerous NHL subtypes with distinct combinations of morphologic, immunophenotypic, genetic, and clinical features are currently recognized (2,3). The incidence of NHL subtypes varies substantially by age, sex, and race/ethnicity (4–7). However, the etiological implications of this biological, clinical, and epidemiological diversity are incompletely understood. The importance of investigating etiology by NHL subtype is clearly supported by research on immunosuppression, infections, and autoimmune diseases, which are the strongest and most established risk factors for NHL. Studies of solid organ transplant recipients and individuals infected with HIV demonstrate that risks are markedly increased for several—but not all—NHL subtypes (8–13). Some infections and autoimmune diseases are associated with a single specific subtype [eg, human T-cell lymphotropic virus, type I (HTLV-I) with adult T-cell leukemia/lymphoma (14), celiac disease with enteropathy-type peripheral T-cell lymphoma (PTCL) (15–17)], whereas others [eg, Epstein–Barr virus, hepatitis C virus (HCV), Sjogren’s syndrome (18–21)] have been associated with multiple subtypes. In the last two decades, reports from individual epidemiological studies of NHL have suggested differences in risks among NHL subtypes for a wide range of risk factors, but most studies have lacked the statistical power to assess any differences quantitatively and have not systematically evaluated combinations of subtypes. One study assessed multiple risk factors and found support for both etiologic commonality and heterogeneity for NHL subtypes, with risk factor patterns suggesting that immune dysfunction is of greater etiologic importance for diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma than for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (22). However, that analysis was limited to approximately 1300 NHL cases and considered only the four most common NHL subtypes. Pooling data from multiple studies through the International Lymphoma Epidemiology Consortium (InterLymph) have provided substantial insight into associations between specific risk factors and NHL subtypes, with evidence that family history of hematologic malignancy, autoimmune diseases, atopic conditions, lifestyle factors (smoking, alcohol, anthropometric measures, and hair dye use), and sun exposure are associated with NHL risk (19,21,23–32). However, no previous study has compared patterns of risk for a range of exposures for both common and rarer NHL subtypes. We undertook the InterLymph NHL Subtypes Project, a pooled analysis of 20 case–control studies including 17 471 NHL cases and 23 096 controls, to advance understanding of NHL etiology by investigating NHL subtype-specific risks associated with medical history, family history of hematologic malignancy, lifestyle factors, and occupation. The detailed risk factor profiles for each of 11 NHL subtypes appear in this issue (15–17,33–40). In this report, we assess risk factor heterogeneity among the NHL subtypes and identify subtypes that have similar risk factor profiles.

Published
2014

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

39. Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes.

Author

Berndt SI, Vijai J, Benavente Y, Camp NJ, Nieters A, Wang Z, Smedby KE, Kleinstern G, Hjalgrim H, Besson C, Skibola CF, Morton LM, Brooks-Wilson AR, Teras LR, Breeze C, Arias J, Adami HO, Albanes D, Anderson KC, Ansell SM, Bassig B, Becker N, Bhatti P, Birmann BM, Boffetta P, Bracci PM, Brennan P, Brown EE, Burdett L, Cannon-Albright LA, Chang ET, Chiu BCH, Chung CC, Clavel J, Cocco P, Colditz G, Conde L, Conti DV, Cox DG, Curtin K, Casabonne D, De Vivo I, Diepstra A, Diver WR, Dogan A, Edlund CK, Foretova L, Fraumeni JF Jr, Gabbas A, Ghesquières H, Giles GG, Glaser S, Glenn M, Glimelius B, Gu J, Habermann TM, Haiman CA, Haioun C, Hofmann JN, Holford TR, Holly EA, Hutchinson A, Izhar A, Jackson RD, Jarrett RF, Kaaks R, Kane E, Kolonel LN, Kong Y, Kraft P, Kricker A, Lake A, Lan Q, Lawrence C, Li D, Liebow M, Link BK, Magnani C, Maynadie M, McKay J, Melbye M, Miligi L, Milne RL, Molina TJ, Monnereau A, Montalvan R, North KE, Novak AJ, Onel K, Purdue MP, Rand KA, Riboli E, Riby J, Roman E, Salles G, Sborov DW, Severson RK, Shanafelt TD, Smith MT, Smith A, Song KW, Song L, Southey MC, Spinelli JJ, Staines A, Stephens D, Sutherland HJ, Tkachuk K, Thompson CA, Tilly H, Tinker LF, Travis RC, Turner J, Vachon CM, Vajdic CM, Van Den Berg A, Van Den Berg DJ, Vermeulen RCH, Vineis P, Wang SS, Weiderpass E, Weiner GJ, Weinstein S, Doo NW, Ye Y, Yeager M, Yu K, Zeleniuch-Jacquotte A, Zhang Y, Zheng T, Ziv E, Sampson J, Chatterjee N, Offit K, Cozen W, Wu X, Cerhan JR, Chanock SJ, Slager SL, and Rothman N

Published
2023
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40. Physical activity and the risk of non-Hodgkin lymphoma subtypes: A pooled analysis.

Author

Boyle T, Kleinstern G, Bracci PM, Cerhan JR, Benavente Y, Casabonne D, Chiu BC, Habermann TM, Holly EA, Liebow M, Norman A, Paltiel O, Robinson D, Rothman N, Abu Seir R, Slager SL, Villeneuve PJ, Wang SS, Weisenburger DD, and Spinelli JJ

Subjects
Humans, Risk Factors, Case-Control Studies, Exercise, Lymphoma, Non-Hodgkin etiology, Lymphoma, Non-Hodgkin complications, Lymphoma, Follicular epidemiology, Lymphoma, Follicular etiology
Abstract

Non-Hodgkin lymphoma (NHL) is composed of a heterogeneous collection of subtypes with considerable differences in genetics, biology and aetiology. Studies to date on physical activity and NHL risk have not had sufficient sample size to evaluate whether associations differ by subtype. We pooled data from nine case-control studies to examine the association between moderate-to-vigorous intensity physical activity (MVPA) and risk of NHL overall and by subtype (diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia/small lymphocytic lymphoma, marginal zone lymphoma and mature T-cell lymphoma). A total of 5653 cases and 9115 controls were included in the pooled analysis. Physical activity was harmonised across nine studies and modelled as study-specific tertiles. Multinomial logistic regression was used to estimate the association between physical activity and NHL, adjusting for confounders. The overall odds of NHL was 13% lower among participants in the most active tertile of MVPA compared to the least active tertile (adjusted odds ratio = 0.87, 95% CI = 0.80, 0.95). Similar decreases were observed across NHL subtypes. In summary, in this pooled analysis of case-control studies, physical activity was associated with a modest risk reduction for each NHL subtype examined and with overall NHL., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Published
2023
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41. Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes.

Author

Berndt SI, Vijai J, Benavente Y, Camp NJ, Nieters A, Wang Z, Smedby KE, Kleinstern G, Hjalgrim H, Besson C, Skibola CF, Morton LM, Brooks-Wilson AR, Teras LR, Breeze C, Arias J, Adami HO, Albanes D, Anderson KC, Ansell SM, Bassig B, Becker N, Bhatti P, Birmann BM, Boffetta P, Bracci PM, Brennan P, Brown EE, Burdett L, Cannon-Albright LA, Chang ET, Chiu BCH, Chung CC, Clavel J, Cocco P, Colditz G, Conde L, Conti DV, Cox DG, Curtin K, Casabonne D, De Vivo I, Diepstra A, Diver WR, Dogan A, Edlund CK, Foretova L, Fraumeni JF Jr, Gabbas A, Ghesquières H, Giles GG, Glaser S, Glenn M, Glimelius B, Gu J, Habermann TM, Haiman CA, Haioun C, Hofmann JN, Holford TR, Holly EA, Hutchinson A, Izhar A, Jackson RD, Jarrett RF, Kaaks R, Kane E, Kolonel LN, Kong Y, Kraft P, Kricker A, Lake A, Lan Q, Lawrence C, Li D, Liebow M, Link BK, Magnani C, Maynadie M, McKay J, Melbye M, Miligi L, Milne RL, Molina TJ, Monnereau A, Montalvan R, North KE, Novak AJ, Onel K, Purdue MP, Rand KA, Riboli E, Riby J, Roman E, Salles G, Sborov DW, Severson RK, Shanafelt TD, Smith MT, Smith A, Song KW, Song L, Southey MC, Spinelli JJ, Staines A, Stephens D, Sutherland HJ, Tkachuk K, Thompson CA, Tilly H, Tinker LF, Travis RC, Turner J, Vachon CM, Vajdic CM, Van Den Berg A, Van Den Berg DJ, Vermeulen RCH, Vineis P, Wang SS, Weiderpass E, Weiner GJ, Weinstein S, Doo NW, Ye Y, Yeager M, Yu K, Zeleniuch-Jacquotte A, Zhang Y, Zheng T, Ziv E, Sampson J, Chatterjee N, Offit K, Cozen W, Wu X, Cerhan JR, Chanock SJ, Slager SL, and Rothman N

Subjects
Humans, Genome-Wide Association Study, Risk Factors, Germ Cells, Case-Control Studies, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Lymphoma, Non-Hodgkin genetics
Abstract

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10 -8 ) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10 -9 ). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10 -8 ), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Published
2022
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42. Aspirin and other nonsteroidal anti-inflammatory drugs, statins and risk of non-Hodgkin lymphoma.

Author

Liebow M, Larson MC, Thompson CA, Nowakowski GS, Call TG, Macon WR, Kay NE, Habermann TM, Slager SL, and Cerhan JR

Subjects
Adult, Aged, Female, Follow-Up Studies, Humans, Incidence, Lymphoma, Non-Hodgkin pathology, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, United States epidemiology, Alcohol Drinking adverse effects, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Aspirin adverse effects, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Lymphoma, Non-Hodgkin epidemiology, Lymphoma, Non-Hodgkin etiology
Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) and statin drugs may protect against the development of non-Hodgkin lymphoma (NHL), but data are limited, particularly for NHL subtypes. Furthermore, some in vitro, animal and epidemiologic data suggest there may be a synergistic effect of these two agents, but there has been no test of this hypothesis in NHL. We evaluated the self-reported use of NSAIDs and statins in a clinic-based study of 1703 NHL patients and 2199 frequency-matched controls. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounding variables. We observed an inverse association of regular use of low-dose aspirin with risk of NHL (OR = 0.82; 95% CI 0.70-0.96) that was stronger with longer duration of use (P < .01). There were no associations for use of regular or extra-strength aspirin, ibuprofen, other NSAIDs, statins or other cholesterol-lowering drugs with NHL risk, while an inverse association with COX-2 inhibitors was equivocal. There was also no interaction of low-dose aspirin and statins on NHL risk. Inverse associations of similar magnitude to all NHL were observed for regular use of low-dose aspirin with diffuse large B-cell, follicular, marginal zone and all other lymphomas, although not all associations were statistically significant. In conclusion, low-dose aspirin but not regular/extra strength aspirin, other NSAIDs or statin use was associated with lower risk of NHL. Beyond the potential for the primary prevention of NHL, these data also point to a role of anti-platelet or other effects of low-dose aspirin in lymphomagenesis that warrant follow-up., (© 2021 Union for International Cancer Control.)

Published
2021
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43. Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes.

Author

Moore A, Machiela MJ, Machado M, Wang SS, Kane E, Slager SL, Zhou W, Carrington M, Lan Q, Milne RL, Birmann BM, Adami HO, Albanes D, Arslan AA, Becker N, Benavente Y, Bisanzi S, Boffetta P, Bracci PM, Brennan P, Brooks-Wilson AR, Canzian F, Caporaso N, Clavel J, Cocco P, Conde L, Cox DG, Cozen W, Curtin K, De Vivo I, de Sanjose S, Foretova L, Gapstur SM, Ghesquières H, Giles GG, Glenn M, Glimelius B, Gao C, Habermann TM, Hjalgrim H, Jackson RD, Liebow M, Link BK, Maynadie M, McKay J, Melbye M, Miligi L, Molina TJ, Monnereau A, Nieters A, North KE, Offit K, Patel AV, Piro S, Ravichandran V, Riboli E, Salles G, Severson RK, Skibola CF, Smedby KE, Southey MC, Spinelli JJ, Staines A, Stewart C, Teras LR, Tinker LF, Travis RC, Vajdic CM, Vermeulen RCH, Vijai J, Weiderpass E, Weinstein S, Doo NW, Zhang Y, Zheng T, Chanock SJ, Rothman N, Cerhan JR, Dean M, Camp NJ, Yeager M, and Berndt SI

Abstract

Aim: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk., Methods: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis., Results: We discovered positive associations between FROH and CLL (β = 21.1, SE = 4.41, P = 1.6 × 10 -6 ) and FL (β = 11.4, SE = 5.82, P = 0.02) but not DLBCL ( P = 1.0) or MZL ( P = 0.91). For F3, we observed an association with CLL (β = 27.5, SE = 6.51, P = 2.4 × 10 -5 ). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity., Conclusion: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk., Competing Interests: Conflicts of interest All authors declare that there are no conflicts of interest.

Published
2021
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44. Perioperative Evaluation and Management of Endocrine Disorders.

Author

Himes CP, Ganesh R, Wight EC, Simha V, and Liebow M

Subjects
Diagnostic Techniques, Endocrine, Humans, Endocrine System Diseases diagnosis, Preoperative Care methods, Risk Adjustment methods, Surgical Procedures, Operative adverse effects, Surgical Procedures, Operative methods
Abstract

Evaluation of endocrine issues is a sometimes overlooked yet important component of the preoperative medical evaluation. Patients with diabetes, thyroid disease, and hypothalamic-pituitary-adrenal axis suppression are commonly encountered in the surgical setting and require unique consideration to optimize perioperative risk. For patients with diabetes, perioperative glycemic control has the strongest association with postsurgical outcomes. The preoperative evaluation should include recommendations for adjustment of insulin and noninsulin diabetic medications before surgery. Recommendations differ based on the type of diabetes, the type of insulin, and the patient's predisposition to hyperglycemia or hypoglycemia. Generally, patients with thyroid dysfunction can safely undergo operations unless they have untreated hyperthyroidism or severe hypothyroidism. Patients with known primary or secondary adrenal insufficiency require supplemental glucocorticoids to prevent adrenal crisis in the perioperative setting. Evidence supporting the use of high-dose supplemental corticosteroids for patients undergoing long-term glucocorticoid therapy is sparse. We discuss an approach to these patients based on the dose and duration of ongoing or recent corticosteroid therapy. As with other components of the preoperative medical evaluation, the primary objective is identification and assessment of the severity of endocrine issues before surgery so that the surgeons, anesthesiologists, and internal medicine professionals can optimize management accordingly., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Published
2020
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45. Human Pegivirus Infection and Lymphoma Risk: A Systematic Review and Meta-analysis.

Author

Fama A, Larson MC, Link BK, Habermann TM, Feldman AL, Call TG, Ansell SM, Liebow M, Xiang J, Maurer MJ, Slager SL, Nowakowski GS, Stapleton JT, and Cerhan JR

Subjects
Adult, Cohort Studies, Europe, Humans, Middle East, North America, Pegivirus, Prevalence, RNA, Viral, Flaviviridae Infections, Lymphoma epidemiology
Abstract

Background: Human pegivirus (HPgV) is a single-strand RNA virus belonging to the Flaviviridae. Although no definitive association between HPgV infection and disease has been identified, previous studies have suggested an association of HPgV viremia with risk of lymphomas., Methods: We conducted a systematic review and meta-analysis, including 1 cohort study and 14 case-control studies, assessing the association of HPgV viremia with adult lymphomas. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model, overall and by geographic region and lymphoma subtype., Results: The overall OR for lymphoma was 2.85 (95% CI, 1.98-4.11), with statistically significantly elevated ORs observed in 8 of 15 studies. There was a small amount of heterogeneity among studies (I2 = 28.9%; Q = 18.27, P = .16), and the funnel plot provided no evidence for publication bias. The strongest association with lymphoma risk was observed for studies from Southern Europe (OR, 5.68 [95% CI, 1.98-16.3]), whereas weaker ORs (with 95% CIs) were observed for studies from North America (2.24 [1.76-2.85]), Northern Europe (2.90 [.45-18.7), and the Middle East (2.51 [.87-7.27]), but all of similar magnitude. Participants with HPgV viremia had statistically significantly increased risks (OR [95% CI]) for developing diffuse large B-cell (3.29 [1.63-6.62]), follicular (3.01 [1.95-4.63]), marginal zone (1.90 [1.13-3.18]), and T-cell (2.11 [1.17-3.89]) lymphomas, while the risk for Hodgkin lymphoma (3.53 [.48-25.9]) and chronic lymphocytic leukemia (1.45 [.45-4.66]) were increased but did not achieve statistical significance., Conclusions: This meta-analysis supports a positive association of HPgV viremia with lymphoma risk, overall and for the major lymphoma subtypes., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Published
2020
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46. Responsibilities, Strategies, and Practice Factors in Clinical Cost Conversations: a US Physician Survey.

Author

Warsame R, Riordan L, Jenkins S, Lackore K, Pacyna J, Antiel R, Beebe T, Liebow M, Thorsteinsdottir B, Grover M, Wynia M, Goold SD, DeCamp M, Danis M, and Tilburt J

Subjects
Attitude of Health Personnel, Communication, Cost Control, Cross-Sectional Studies, Humans, Surveys and Questionnaires, Physicians
Abstract

Background: Physicians play a key role in mitigating and managing costs in healthcare which are rising., Objective: Conduct a cross-sectional survey in 2017, comparing results to a 2012 survey to understand US physicians' evolving attitudes and strategies concerning healthcare costs., Participants: Random sample of 1200 US physicians from the AMA Masterfile., Measures: Physician views on responsibility for costs of care, enthusiasm for cost-saving strategies, cost-consciousness scale, and practice strategies on addressing cost., Key Results: Among 1200 physicians surveyed in 2017, 489 responded (41%). In 2017, slightly more physicians reported that physicians have a major responsibility for addressing healthcare costs (32% vs. 27%, p = 0.03). In 2017, more physicians attributed "major responsibility" for addressing healthcare costs to pharmaceutical companies (68% vs. 56%, p < 0.001) and hospital and health systems (63% vs. 56%%, p = 0.008) in contrast to 2012. Fewer respondents in 2017 attributed major responsibility for addressing costs to trial lawyers (53% vs. 59%, p = 0.007) and patients (42% vs. 52%, p < 0.0001) as compared to 2012. Physician enthusiasm for patient-focused cost-containment strategies like high deductible health plans and higher co-pays (62% vs. 42%, p < 0.0001 and 62% vs. 39%, p < 0.0001, not enthusiastic, respectively) declined. Physicians reported that when they discussed cost, it resulted in a change in disease management 56% of the time. Cost-consciousness within surveyed physicians had not changed meaningfully in 2017 since 2012 (31.7 vs. 31.2). Most physicians continued to agree that decision support tools showing costs would be helpful in their practice (> 70%). After adjusting for specialty, political affiliation, practice setting, age, and gender, only democratic/independent affiliation remained a significant predictor of cost-consciousness., Conclusions and Relevance: US physicians increasingly attribute responsibility for rising healthcare costs to organizations and express less enthusiasm for strategies that increase patient out-of-pocket cost. Interventions that focus on physician knowledge and communication strategies regarding cost of care may be helpful.

Published
2020
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48. Genetically Determined Height and Risk of Non-hodgkin Lymphoma.

Author

Moore A, Kane E, Wang Z, Panagiotou OA, Teras LR, Monnereau A, Wong Doo N, Machiela MJ, Skibola CF, Slager SL, Salles G, Camp NJ, Bracci PM, Nieters A, Vermeulen RCH, Vijai J, Smedby KE, Zhang Y, Vajdic CM, Cozen W, Spinelli JJ, Hjalgrim H, Giles GG, Link BK, Clavel J, Arslan AA, Purdue MP, Tinker LF, Albanes D, Ferri GM, Habermann TM, Adami HO, Becker N, Benavente Y, Bisanzi S, Boffetta P, Brennan P, Brooks-Wilson AR, Canzian F, Conde L, Cox DG, Curtin K, Foretova L, Gapstur SM, Ghesquières H, Glenn M, Glimelius B, Jackson RD, Lan Q, Liebow M, Maynadie M, McKay J, Melbye M, Miligi L, Milne RL, Molina TJ, Morton LM, North KE, Offit K, Padoan M, Patel AV, Piro S, Ravichandran V, Riboli E, de Sanjose S, Severson RK, Southey MC, Staines A, Stewart C, Travis RC, Weiderpass E, Weinstein S, Zheng T, Chanock SJ, Chatterjee N, Rothman N, Birmann BM, Cerhan JR, and Berndt SI

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., (Copyright © 2020 Moore, Kane, Wang, Panagiotou, Teras, Monnereau, Wong Doo, Machiela, Skibola, Slager, Salles, Camp, Bracci, Nieters, Vermeulen, Vijai, Smedby, Zhang, Vajdic, Cozen, Spinelli, Hjalgrim, Giles, Link, Clavel, Arslan, Purdue, Tinker, Albanes, Ferri, Habermann, Adami, Becker, Benavente, Bisanzi, Boffetta, Brennan, Brooks-Wilson, Canzian, Conde, Cox, Curtin, Foretova, Gapstur, Ghesquières, Glenn, Glimelius, Jackson, Lan, Liebow, Maynadie, McKay, Melbye, Miligi, Milne, Molina, Morton, North, Offit, Padoan, Patel, Piro, Ravichandran, Riboli, de Sanjose, Severson, Southey, Staines, Stewart, Travis, Weiderpass, Weinstein, Zheng, Chanock, Chatterjee, Rothman, Birmann, Cerhan and Berndt.)

Published
2020
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49. Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

Author

Din L, Sheikh M, Kosaraju N, Smedby KE, Bernatsky S, Berndt SI, Skibola CF, Nieters A, Wang S, McKay JD, Cocco P, Maynadié M, Foretová L, Staines A, Mack TM, de Sanjosé S, Vyse TJ, Padyukov L, Monnereau A, Arslan AA, Moore A, Brooks-Wilson AR, Novak AJ, Glimelius B, Birmann BM, Link BK, Stewart C, Vajdic CM, Haioun C, Magnani C, Conti DV, Cox DG, Casabonne D, Albanes D, Kane E, Roman E, Muzi G, Salles G, Giles GG, Adami HO, Ghesquières H, De Vivo I, Clavel J, Cerhan JR, Spinelli JJ, Hofmann J, Vijai J, Curtin K, Costenbader KH, Onel K, Offit K, Teras LR, Morton L, Conde L, Miligi L, Melbye M, Ennas MG, Liebow M, Purdue MP, Glenn M, Southey MC, Din M, Rothman N, Camp NJ, Wong Doo N, Becker N, Pradhan N, Bracci PM, Boffetta P, Vineis P, Brennan P, Kraft P, Lan Q, Severson RK, Vermeulen RCH, Milne RL, Kaaks R, Travis RC, Weinstein SJ, Chanock SJ, Ansell SM, Slager SL, Zheng T, Zhang Y, Benavente Y, Taub Z, Madireddy L, Gourraud PA, Oksenberg JR, Cozen W, Hjalgrim H, and Khankhanian P

Subjects
Alleles, Female, HLA Antigens genetics, Humans, Male, Middle Aged, Multifactorial Inheritance genetics, Polymorphism, Single Nucleotide genetics, Risk Factors, Autoimmune Diseases genetics, Genetic Predisposition to Disease, Lymphoma, Non-Hodgkin genetics
Abstract

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., (© 2019 Wiley Periodicals, Inc.)

Published
2019
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50. US Physicians' Reactions To ACA Implementation, 2012-17.

Author

Riordan L, Warsame R, Jenkins S, Lackore K, Pacyna JE, Antiel RM, Beebe T, Liebow M, Thorsteinsdottir B, Wynia M, Goold SD, DeCamp M, Danis M, and Tilburt J

Subjects
Female, Humans, Male, Middle Aged, Surveys and Questionnaires, Attitude of Health Personnel, Patient Protection and Affordable Care Act, Physicians psychology
Abstract

Physicians play a key role in implementing health policy, and US physicians were split in their opinions about the Affordable Care Act (ACA) soon after its implementation began. We readministered elements of a prior survey of US physicians to a similar sample to understand how US physicians' opinions of the ACA may have changed over a crucial five-year implementation period (2012-17), and we compared responses across both surveys. Of the 1,200 physicians to whom we sent a survey in the summer of 2017, 489 responded (a response rate of 41 percent). A majority of respondents (60 percent) believed that the ACA had improved access to care and insurance, yet many (43 percent) felt that it had reduced the affordability of coverage. More physicians agreed in 2017 than in 2012 that the ACA "would turn United States health care in the right direction" (53 percent versus 42 percent), despite reporting perceived worsening in several practice conditions over the same time period. After we adjusted for specialty, political party affiliation, practice setting type, perceived social responsibility, age, and sex, we found that only political party affiliation was a significant predictor of support for the ACA in the 2017 results.

Published
2019
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