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Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia.


ABSTRACT: Prognostication in patients with chronic lymphocytic leukemia (CLL) is challenging due to heterogeneity in clinical course. We hypothesize that constitutional genetic variation affects disease progression and could aid prognostication. Pooling data from seven studies incorporating 842 cases identifies two genomic locations associated with time from diagnosis to treatment, including 10q26.13 (rs736456, hazard ratio (HR)?=?1.78, 95% confidence interval (CI)?=?1.47-2.15; P?=?2.71?×?10-9) and 6p (rs3778076, HR?=?1.99, 95% CI?=?1.55-2.55; P?=?5.08?×?10-8), which are particularly powerful prognostic markers in patients with early stage CLL otherwise characterized by low-risk features. Expression quantitative trait loci analysis identifies putative functional genes implicated in modulating B-cell receptor or innate immune responses, key pathways in CLL pathogenesis. In this work we identify rs736456 and rs3778076 as prognostic in CLL, demonstrating that disease progression is determined by constitutional genetic variation as well as known somatic drivers.

SUBMITTER: Lin WY 

PROVIDER: S-EPMC7843618 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia.

Lin Wei-Yu WY   Fordham Sarah E SE   Sunter Nicola N   Elstob Claire C   Rahman Thahira T   Willmore Elaine E   Shepherd Colin C   Strathdee Gordon G   Mainou-Fowler Tryfonia T   Piddock Rachel R   Mearns Hannah H   Barrow Timothy T   Houlston Richard S RS   Marr Helen H   Wallis Jonathan J   Summerfield Geoffrey G   Marshall Scott S   Pettitt Andrew A   Pepper Christopher C   Fegan Christopher C   Forconi Francesco F   Dyer Martin J S MJS   Jayne Sandrine S   Sellors April A   Schuh Anna A   Robbe Pauline P   Oscier David D   Bailey James J   Rais Syed S   Bentley Alison A   Cawkwell Lynn L   Evans Paul P   Hillmen Peter P   Pratt Guy G   Allsup David J DJ   Allan James M JM  

Nature communications 20210128 1


Prognostication in patients with chronic lymphocytic leukemia (CLL) is challenging due to heterogeneity in clinical course. We hypothesize that constitutional genetic variation affects disease progression and could aid prognostication. Pooling data from seven studies incorporating 842 cases identifies two genomic locations associated with time from diagnosis to treatment, including 10q26.13 (rs736456, hazard ratio (HR) = 1.78, 95% confidence interval (CI) = 1.47-2.15; P = 2.71 × 10<sup>-9</sup>)  ...[more]

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