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

Autor: Colin Shepherd, Nicola J. Sunter, Paul G. Evans, Rachel Piddock, David Allsup, Helen Marr, Scott Marshall, Claire Elstob, Francesco Forconi, Richard S. Houlston, Syed Ashar Rais, Tryfonia Mainou-Fowler, Thahira Rahman, April Sellors, Chris Pepper, Sandrine Jayne, Alison Bentley, Sarah E. Fordham, Christopher Fegan, Anna Schuh, Peter Hillmen, Martin J. S. Dyer, David Oscier, Wei-Yu Lin, James M. Allan, Lynn Cawkwell, Jonathan P. Wallis, Guy Pratt, James R. Bailey, Geoffrey Summerfield, Andrew R. Pettitt, Gordon Strathdee, Elaine Willmore, Hannah Mearns, Pauline Robbe, Timothy M. Barrow
Rok vydání: 2019
Předmět:
0301 basic medicine
Oncology
Male
medicine.medical_specialty
Chronic lymphocytic leukaemia
Chronic lymphocytic leukemia
Science
Quantitative Trait Loci
General Physics and Astronomy
Genome-wide association study
Kaplan-Meier Estimate
Polymorphism
Single Nucleotide
General Biochemistry
Genetics and Molecular Biology
Article
Pathogenesis
03 medical and health sciences
Prognostic markers
0302 clinical medicine
Polymorphism (computer science)
immune system diseases
Internal medicine
hemic and lymphatic diseases
Genetic variation
Cancer genomics
Medicine
Humans
Genetic Predisposition to Disease
Cancer genetics
Aged
Multidisciplinary
business.industry
Hazard ratio
General Chemistry
Middle Aged
medicine.disease
Prognosis
Leukemia
Lymphocytic
Chronic
B-Cell
Leukemia
030104 developmental biology
030220 oncology & carcinogenesis
Expression quantitative trait loci
Multivariate Analysis
Disease Progression
Genetic markers
Female
business
Genome-Wide Association Study
Zdroj: Nature Communications
Nature Communications, Vol 12, Iss 1, Pp 1-8 (2021)
ISSN: 2041-1723
Popis: 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.
The clinical course of chronic lymphocytic leukaemia (CLL) is variable and difficult to predict. Here, the authors conduct a genome wide association study meta-analysis for time to first treatment in CLL patients and report two loci associating with progressive disease.
Databáze: OpenAIRE
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