TY - JOUR
T1 - Genetic association with B-cell acute lymphoblastic leukemia in allogeneic transplant patients differs by age and sex
AU - Clay-Gilmour, Alyssa I.
AU - Hahn, Theresa
AU - Preus, Leah M.
AU - Onel, Kenan
AU - Skol, Andrew
AU - Hungate, Eric
AU - Zhu, Qianqian
AU - Haiman, Christopher A.
AU - Stram, Daniel O.
AU - Pooler, Loreall
AU - Sheng, Xin
AU - Yan, Li
AU - Liu, Qian
AU - Hu, Qiang
AU - Liu, Song
AU - Battaglia, Sebastiano
AU - Zhu, Xiaochun
AU - Block, Anne Marie W.
AU - Sait, Sheila N.J.
AU - Karaesmen, Ezgi
AU - Rizvi, Abbas
AU - Weisdorf, Daniel J.
AU - Ambrosone, Christine B.
AU - Tritchler, David
AU - Ellinghaus, Eva
AU - Ellinghaus, David
AU - Stanulla, Martin
AU - Clavel, Jacqueline
AU - Orsi, Laurent
AU - Spellman, Stephen
AU - Pasquini, Marcelo C.
AU - McCarthy, Philip L.
AU - Sucheston-Campbell, Lara E.
N1 - Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/9/12
Y1 - 2017/9/12
N2 - The incidence and mortality rates of B-cell acute lymphoblastic leukemia (B-ALL) differ by age and sex. To determine if inherited genetic susceptibility contributes to these differences we performed 2 genome-wide association studies (GWAS) by age, sex, and subtype and subsequent meta-analyses. The GWAS included 446 B-ALL cases, and 3027 healthy unrelated blood and marrow transplant (BMT) donors as controls from the Determining the Influence of Susceptibility Conveying Variants Related to One-Year Mortality after BMT (DISCOVeRY-BMT) study. We identified 1 novel variant, rs189434316, significantly associated with odds of normal cytogenetic B-ALL (odds ratio from meta-analysis [ORmeta] 5 3.7; 95% confidence interval [CI], 2.5, 6.2; P value from meta-analysis [Pmeta] 5 6.0 3 1029). The previously reported pediatric B-ALL GWAS variant, rs11980379 (IKZF1), replicated in B-ALL pediatric patients (ORmeta 5 2.3; 95% CI, 1.5, 3.7; Pmeta 5 1.0 3 1029), with evidence of heterogeneity (P 5 .02) between males and females. Sex differences in single-nucleotide polymorphism effect were seen in those .15 years (OR 5 1.7; 95% CI, 1.4, 2.2, PMales 5 6.38 3 1026/OR 5 1.1; 95% CI, 0.8, 1.5; PFemales 5 .6) but not #15 years (OR 5 2.3; 95% CI, 1.4, 3.8; PMales 5 .0007/OR 5 1.9; 95% CI, 1.2, 3.2; PFemales 5 .007). The latter association replicated in independent pediatric B-ALL cohorts. A previously identified adolescent and young-adult onset ALL-associated variant in GATA3 is associated with B-ALL risk in those .40 years. Our findings provide more evidence of the influence of genetics on B-ALL age of onset and we have shown the first evidence that IKZF1 associations with B-ALL may be sex and age specific.
AB - The incidence and mortality rates of B-cell acute lymphoblastic leukemia (B-ALL) differ by age and sex. To determine if inherited genetic susceptibility contributes to these differences we performed 2 genome-wide association studies (GWAS) by age, sex, and subtype and subsequent meta-analyses. The GWAS included 446 B-ALL cases, and 3027 healthy unrelated blood and marrow transplant (BMT) donors as controls from the Determining the Influence of Susceptibility Conveying Variants Related to One-Year Mortality after BMT (DISCOVeRY-BMT) study. We identified 1 novel variant, rs189434316, significantly associated with odds of normal cytogenetic B-ALL (odds ratio from meta-analysis [ORmeta] 5 3.7; 95% confidence interval [CI], 2.5, 6.2; P value from meta-analysis [Pmeta] 5 6.0 3 1029). The previously reported pediatric B-ALL GWAS variant, rs11980379 (IKZF1), replicated in B-ALL pediatric patients (ORmeta 5 2.3; 95% CI, 1.5, 3.7; Pmeta 5 1.0 3 1029), with evidence of heterogeneity (P 5 .02) between males and females. Sex differences in single-nucleotide polymorphism effect were seen in those .15 years (OR 5 1.7; 95% CI, 1.4, 2.2, PMales 5 6.38 3 1026/OR 5 1.1; 95% CI, 0.8, 1.5; PFemales 5 .6) but not #15 years (OR 5 2.3; 95% CI, 1.4, 3.8; PMales 5 .0007/OR 5 1.9; 95% CI, 1.2, 3.2; PFemales 5 .007). The latter association replicated in independent pediatric B-ALL cohorts. A previously identified adolescent and young-adult onset ALL-associated variant in GATA3 is associated with B-ALL risk in those .40 years. Our findings provide more evidence of the influence of genetics on B-ALL age of onset and we have shown the first evidence that IKZF1 associations with B-ALL may be sex and age specific.
UR - https://www.scopus.com/pages/publications/85063396707
U2 - 10.1182/bloodadvances.2017006023
DO - 10.1182/bloodadvances.2017006023
M3 - Article
AN - SCOPUS:85063396707
SN - 2473-9529
VL - 1
SP - 1717
EP - 1728
JO - Blood Advances
JF - Blood Advances
IS - 20
ER -