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1. 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

2. 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

3. 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

4. ITMIG Consensus Statement on the Use of the WHO Histological Classification of Thymoma and Thymic Carcinoma: Refined Definitions, Histological Criteria, and Reporting

Author

Marx, A, Strobel, P, Badve, S, Chalabreysse, L, Chan, Jk, Chen, G, De Leval, L, Detterbeck, F, Girard, N, Huang, J, Kurrer, Mo, Lauriola, Libero, Marino, M, Matsuno, Y, Molina, Tj, Mukai, K, Nicholson, Ag, Nonaka, D, Rieker, R, Rosai, J, Ruffini, E, Travis, Wd, Lauriola, Libero (ORCID:0000-0003-0481-5138), Marx, A, Strobel, P, Badve, S, Chalabreysse, L, Chan, Jk, Chen, G, De Leval, L, Detterbeck, F, Girard, N, Huang, J, Kurrer, Mo, Lauriola, Libero, Marino, M, Matsuno, Y, Molina, Tj, Mukai, K, Nicholson, Ag, Nonaka, D, Rieker, R, Rosai, J, Ruffini, E, Travis, Wd, and Lauriola, Libero (ORCID:0000-0003-0481-5138)

Abstract

INTRODUCTION: The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) thymomas and thymic carcinomas (TC). Due to a morphological continuum between some thymoma subtypes and some morphological overlap between thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies.METHODS: To overcome this problem, hematoxylin-eosin-stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" thymomas and TC (n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group.RESULTS: Consensus was achieved on refined criteria for decision making at the A/AB borderland, the distinction between B1, B2, and B3 thymomas and the separation of B3 thymomas from TCs. "Atypical type A thymoma" is tentatively proposed as a new type A thymoma variant. New reporting strategies for tumors with more than one histological pattern are proposed.CONCLUSION: These guidelines can set the stage for reproducibility studies and the design of a clinically meaningful grading system for thymic epithelial tumors.

Published
2014

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