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Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia

Permanent lenke
https://hdl.handle.net/10037/16576
DOI
https://doi.org/10.1038/s41467-018-06541-2
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article.pdf (1.343Mb)
Publisher's version (PDF)
Dato
2018-10-10
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
McMaster, Mary L.; Berndt, Sonja I.; Zhang, Jianqing; Slager, Susan L.; Li, Shengchao Alfred; Vajdic, Claire M.; Smedby, Karin E.; Yan, Huihuang; Birmann, Brenda M.; Brown, Elizabeth E.; Smith, Alex; Kleinstern, Geffen; Fansler, Mervin M.; Mayr, Christine; Zhu, Bin; Chung, Charles C.; Park, Ju-Hyun; Burdette, Laurie; Hicks, Belynda D.; Hutchinson, Amy; Teras, Lauren R.; Adami, Hans Olov; Bracci, Paige M.; McKay, James; Monnereau, Alain; Link, Brian K.; Vermeulen, Roel C.H.; Ansell, Stephen M.; Maria, Ann; Diver, W. Ryan; Melbye, Mads; Ojesina, Akinyemi I.; Kraft, Peter; Boffetta, Paolo; Clavel, Jacqueline; Giovannucci, Edward; Besson, Caroline M.; Canzian, Federico; Travis, Ruth C.; Vineis, Paolo; Weiderpass, Elisabete; Montalvan, Rebecca; Wang, Zhaoming; Yeager, Meredith; Becker, Nikolaus; Benavente, Yolanda; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Nieters, Alexandra; de Sanjose, Silvia; Staines, Anthony; Conde, Lucia; Riby, Jacques; Glimelius, Bengt; Hjalgrim, Henrik; Pradhan, Nisha; Feldman, Andrew L.; Novak, Anne J.; Lawrence, Charles; Bassig, Bryan A.; Lan, Qing; Zheng, Tongzhang; North, Kari E.; Tinker, Lesley F.; Cozen, Wendy; Severson, Richard K.; Hofmann, Jonathan N.; Zhang, Yawei; Jackson, Rebecca D.; Morton, Lindsay M.; Purdue, Mark P.; Chatterjee, Nilanjan; Offit, Kenneth; Cerhan, James R.; Chanock, Stephen J.; Rothman, Nathaniel; Vijai, Joseph; Goldin, Lynn R.; Skibola, Christine F.; Caporaso, Neil E.
Sammendrag
Waldenström 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 × 10−54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45–6.96, P = 8.75 × 10−19). Both risk alleles are observed at a low frequency among controls (~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.
Beskrivelse
Source at https://doi.org/10.1038/s41467-018-06541-2.
Forlag
Springer Nature
Sitering
McMaster, M.L., Berndt, S.I., Zhang, J., Slager, S.L., Li, S.A., Vajdic, C.M., ... Caporaso, N.E. (2018). Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia. Nature Communications, 9, 4182. https://doi.org/10.1038/s41467-018-06541-2
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uit.no/ub - munin@ub.uit.no