Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenstrom macroglobulinemia
Authors
MCMASTER, M. L. (guarantor), S. I. BERNDT, J. ZHANG, S. L. SLAGER, S. A. LI, C. M. VAJDIC, K. E. SMEDBY, H. YAN, B. M. BIRMANN, E. E. BROWN, A. SMITH, G. KLEINSTERN, M. M. FANSLER, C. MAYR, B. ZHU, C. C. CHUNG, J. H. PARK, L. BURDETTE, B. D. HICKS, A. HUTCHINSON, L. R. TERAS, H. O. ADAMI, P. M. BRACCI, J. MCKAY, A. MONNEREAU, B. K. LINK, R. C. H. VERMEULEN, S. M. ANSELL, A. MARIA, W. R. DIVER, M. MELBYE, A. I. OJESINA, P. KRAFT, P. BOFFETTA, J. CLAVEL, E. GIOVANNUCCI, C. M. BESSON, F. CANZIAN, R. C. TRAVIS, P. VINEIS, E. WEIDERPASS, R. MONTALVAN, Z. WANG, M. YEAGER, N. BECKER, Y. BENAVENTE, P. BRENNAN, Lenka FORETOVÁ (203 Czech Republic, belonging to the institution), M. MAYNADIE, A. NIETERS, S. DE SANJOSE, A. STAINES, L. CONDE, J. RIBY, B. GLIMELIUS, H. HJALGRIM, N. PRADHAN, A. L. FELDMAN, A. J. NOVAK, C. LAWRENCE, B. A. BASSIG, Q. LAN, T. ZHENG, K. E. NORTH, L. F. TINKER, W. COZEN, R. K. SEVERSON, J. N. HOFMANN, Y. ZHANG, R. D. JACKSON, L. M. MORTON, M. P. PURDUE, N. CHATTERJEE, K. OFFIT, J. R. CERHAN, S. J. CHANOCK, N. ROTHMAN, J. VIJAI, L. R. GOLDIN, C. F. SKIBOLA and N. E. CAPORASO
Waldenstrom macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P=1.36 x 10(-)(54)) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 x 10(-)(19)) . Both risk alleles are observed at a low frequency among controls (similar to 2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.
MCMASTER, M. L., S. I. BERNDT, J. ZHANG, S. L. SLAGER, S. A. LI, C. M. VAJDIC, K. E. SMEDBY, H. YAN, B. M. BIRMANN, E. E. BROWN, A. SMITH, G. KLEINSTERN, M. M. FANSLER, C. MAYR, B. ZHU, C. C. CHUNG, J. H. PARK, L. BURDETTE, B. D. HICKS, A. HUTCHINSON, L. R. TERAS, H. O. ADAMI, P. M. BRACCI, J. MCKAY, A. MONNEREAU, B. K. LINK, R. C. H. VERMEULEN, S. M. ANSELL, A. MARIA, W. R. DIVER, M. MELBYE, A. I. OJESINA, P. KRAFT, P. BOFFETTA, J. CLAVEL, E. GIOVANNUCCI, C. M. BESSON, F. CANZIAN, R. C. TRAVIS, P. VINEIS, E. WEIDERPASS, R. MONTALVAN, Z. WANG, M. YEAGER, N. BECKER, Y. BENAVENTE, P. BRENNAN, Lenka FORETOVÁ, M. MAYNADIE, A. NIETERS, S. DE SANJOSE, A. STAINES, L. CONDE, J. RIBY, B. GLIMELIUS, H. HJALGRIM, N. PRADHAN, A. L. FELDMAN, A. J. NOVAK, C. LAWRENCE, B. A. BASSIG, Q. LAN, T. ZHENG, K. E. NORTH, L. F. TINKER, W. COZEN, R. K. SEVERSON, J. N. HOFMANN, Y. ZHANG, R. D. JACKSON, L. M. MORTON, M. P. PURDUE, N. CHATTERJEE, K. OFFIT, J. R. CERHAN, S. J. CHANOCK, N. ROTHMAN, J. VIJAI, L. R. GOLDIN, C. F. SKIBOLA and N. E. CAPORASO. Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenstrom macroglobulinemia. Nature Communications. Berlin: Nature, 2018, vol. 9, OCT 2018, p. 1-12. ISSN 2041-1723. Available from: https://dx.doi.org/10.1038/s41467-018-06541-2.
@article{1854525, author = {McMaster, M. L. and Berndt, S. I. and Zhang, J. and Slager, S. L. and Li, S. A. and Vajdic, C. M. and Smedby, K. E. and Yan, H. and Birmann, B. M. and Brown, E. E. and Smith, A. and Kleinstern, G. and Fansler, M. M. and Mayr, C. and Zhu, B. and Chung, C. C. and Park, J. H. and Burdette, L. and Hicks, B. D. and Hutchinson, A. and Teras, L. R. and Adami, H. O. and Bracci, P. M. and McKay, J. and Monnereau, A. and Link, B. K. and Vermeulen, R. C. H. and Ansell, S. M. and Maria, A. and Diver, W. R. and Melbye, M. and Ojesina, A. I. and Kraft, P. and Boffetta, P. and Clavel, J. and Giovannucci, E. and Besson, C. M. and Canzian, F. and Travis, R. C. and Vineis, P. and Weiderpass, E. and Montalvan, R. and Wang, Z. and Yeager, M. and Becker, N. and Benavente, Y. and Brennan, P. and Foretová, Lenka and Maynadie, M. and Nieters, A. and de Sanjose, S. and Staines, A. and Conde, L. and Riby, J. and Glimelius, B. and Hjalgrim, H. and Pradhan, N. and Feldman, A. L. and Novak, A. J. and Lawrence, C. and Bassig, B. A. and Lan, Q. and Zheng, T. and North, K. E. and Tinker, L. F. and Cozen, W. and Severson, R. K. and Hofmann, J. N. and Zhang, Y. and Jackson, R. D. and Morton, L. M. and Purdue, M. P. and Chatterjee, N. and Offit, K. and Cerhan, J. R. and Chanock, S. J. and Rothman, N. and Vijai, J. and Goldin, L. R. and Skibola, C. F. and Caporaso, N. E.}, article_location = {Berlin}, article_number = {OCT 2018}, doi = {http://dx.doi.org/10.1038/s41467-018-06541-2}, keywords = {B-cell lymphoma; Cancer epidemiology; Genome-wide association studies; miRNAs}, language = {eng}, issn = {2041-1723}, journal = {Nature Communications}, title = {Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenstrom macroglobulinemia}, url = {https://www.nature.com/articles/s41467-018-06541-2}, volume = {9}, year = {2018} }
TY - JOUR ID - 1854525 AU - McMaster, M. L. - Berndt, S. I. - Zhang, J. - Slager, S. L. - Li, S. A. - Vajdic, C. M. - Smedby, K. E. - Yan, H. - Birmann, B. M. - Brown, E. E. - Smith, A. - Kleinstern, G. - Fansler, M. M. - Mayr, C. - Zhu, B. - Chung, C. C. - Park, J. H. - Burdette, L. - Hicks, B. D. - Hutchinson, A. - Teras, L. R. - Adami, H. O. - Bracci, P. M. - McKay, J. - Monnereau, A. - Link, B. K. - Vermeulen, R. C. H. - Ansell, S. M. - Maria, A. - Diver, W. R. - Melbye, M. - Ojesina, A. I. - Kraft, P. - Boffetta, P. - Clavel, J. - Giovannucci, E. - Besson, C. M. - Canzian, F. - Travis, R. C. - Vineis, P. - Weiderpass, E. - Montalvan, R. - Wang, Z. - Yeager, M. - Becker, N. - Benavente, Y. - Brennan, P. - Foretová, Lenka - Maynadie, M. - Nieters, A. - de Sanjose, S. - Staines, A. - Conde, L. - Riby, J. - Glimelius, B. - Hjalgrim, H. - Pradhan, N. - Feldman, A. L. - Novak, A. J. - Lawrence, C. - Bassig, B. A. - Lan, Q. - Zheng, T. - North, K. E. - Tinker, L. F. - Cozen, W. - Severson, R. K. - Hofmann, J. N. - Zhang, Y. - Jackson, R. D. - Morton, L. M. - Purdue, M. P. - Chatterjee, N. - Offit, K. - Cerhan, J. R. - Chanock, S. J. - Rothman, N. - Vijai, J. - Goldin, L. R. - Skibola, C. F. - Caporaso, N. E. PY - 2018 TI - Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenstrom macroglobulinemia JF - Nature Communications VL - 9 IS - OCT 2018 SP - 1-12 EP - 1-12 PB - Nature SN - 20411723 KW - B-cell lymphoma KW - Cancer epidemiology KW - Genome-wide association studies KW - miRNAs UR - https://www.nature.com/articles/s41467-018-06541-2 N2 - Waldenstrom macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P=1.36 x 10(-)(54)) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 x 10(-)(19)) . Both risk alleles are observed at a low frequency among controls (similar to 2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy. ER -
MCMASTER, M. L., S. I. BERNDT, J. ZHANG, S. L. SLAGER, S. A. LI, C. M. VAJDIC, K. E. SMEDBY, H. YAN, B. M. BIRMANN, E. E. BROWN, A. SMITH, G. KLEINSTERN, M. M. FANSLER, C. MAYR, B. ZHU, C. C. CHUNG, J. H. PARK, L. BURDETTE, B. D. HICKS, A. HUTCHINSON, L. R. TERAS, H. O. ADAMI, P. M. BRACCI, J. MCKAY, A. MONNEREAU, B. K. LINK, R. C. H. VERMEULEN, S. M. ANSELL, A. MARIA, W. R. DIVER, M. MELBYE, A. I. OJESINA, P. KRAFT, P. BOFFETTA, J. CLAVEL, E. GIOVANNUCCI, C. M. BESSON, F. CANZIAN, R. C. TRAVIS, P. VINEIS, E. WEIDERPASS, R. MONTALVAN, Z. WANG, M. YEAGER, N. BECKER, Y. BENAVENTE, P. BRENNAN, Lenka FORETOVÁ, M. MAYNADIE, A. NIETERS, S. DE SANJOSE, A. STAINES, L. CONDE, J. RIBY, B. GLIMELIUS, H. HJALGRIM, N. PRADHAN, A. L. FELDMAN, A. J. NOVAK, C. LAWRENCE, B. A. BASSIG, Q. LAN, T. ZHENG, K. E. NORTH, L. F. TINKER, W. COZEN, R. K. SEVERSON, J. N. HOFMANN, Y. ZHANG, R. D. JACKSON, L. M. MORTON, M. P. PURDUE, N. CHATTERJEE, K. OFFIT, J. R. CERHAN, S. J. CHANOCK, N. ROTHMAN, J. VIJAI, L. R. GOLDIN, C. F. SKIBOLA and N. E. CAPORASO. Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenstrom macroglobulinemia. \textit{Nature Communications}. Berlin: Nature, 2018, vol.~9, OCT 2018, p.~1-12. ISSN~2041-1723. Available from: https://dx.doi.org/10.1038/s41467-018-06541-2.