Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia.
case_control · Level III
Where this comes from
- Record sourced from PubMed, PMID 33510140.
- Also identified by DOI 10.1038/s41467-020-20822-9 and PMC identifier 7843618.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-9</sup>) and 6p (rs3778076, HR = 1.99, 95% CI = 1.55-2.55; P = 5.08 × 10<sup>-8</sup>), 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.
Medical subject headings
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Leukemia, Lymphocytic, Chronic, B-Cell
- Polymorphism, Single Nucleotide