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

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.; Canzia, 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.

doi:10.1038/s41467-018-06541-2

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

McMaster, Mary L.;
Berndt, Sonja, I;
Zhang, Jianqing;
Slager, Susan L.;
Li, Shengchao Alfred;
... Park, Ju-Hyun;
외 75명

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초록

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.

키워드

GENOME-WIDE ASSOCIATION; B-CELL LYMPHOMA; LYMPHOPLASMACYTIC LYMPHOMA/WALDENSTROM MACROGLOBULINEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; GERMINAL CENTER B; HIGH-RESOLUTION; FAMILIAL AGGREGATION; EXPRESSION PATTERNS; RAL GTPASES

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

저자: 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.; Canzia, 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.

DOI: 10.1038/s41467-018-06541-2

발행일: 2018-10-10

유형: Article

저널명: Nature Communications

권: 9

호: 1

언어: ENG

출판사: NATURE PUBLISHING GROUP

발행국가: 영국

ISSN: E 2041-1723
P 2041-1723