BACKGROUND: There is variability in the outcome of patients with chronic lymphocytic leukemia with apparently the same stage of disease. Identifying genetic variants that influence patients' outcome and response to treatment may provide important insights into the biology of the disease. DESIGN AND METHODS: We investigated the possibility that genetic variation influences outcome by conducting a genome-wide analysis of 346,831 single nucleotide polymorphisms in 356 patients entered into a phase III trial comparing the efficacy of fludarabine, chlorambucil, and fludarabine with cyclophosphamide as first-line treatment. Genotypes were linked to individual patients' outcome data and response to chemotherapy. The association between genotype and progression-free survival was assessed by Cox regression analysis adjusting for treatment and clinicopathology. RESULTS: The strongest associations were shown for rs1949733 (ACOX3; P=8.22x10-7), rs1342899 (P=7.72×10(-7)) and rs11158493 (PPP2R5E; P=8.50×10(-7)). In addition, the 52 single nucleotide polymorphisms associated at P<10(-4) included rs438034 (CENPF; P=4.86×10(-6)), previously correlated with cancer progression, and rs2255235 (B2M; P=3.10×10(-5)) and rs2064501 (IL22RA2; P=4.81×10(-5)) which map to B-cell genes. CONCLUSIONS: Our findings provide evidence that genetic variation is a determinant of progression-free survival of patients with chronic lymphocytic leukemia. Specific associations warrant further analyses.
BACKGROUND: There is variability in the outcome of patients with chronic lymphocytic leukemia with apparently the same stage of disease. Identifying genetic variants that influence patients' outcome and response to treatment may provide important insights into the biology of the disease. DESIGN AND METHODS: We investigated the possibility that genetic variation influences outcome by conducting a genome-wide analysis of 346,831 single nucleotide polymorphisms in 356 patients entered into a phase III trial comparing the efficacy of fludarabine, chlorambucil, and fludarabine with cyclophosphamide as first-line treatment. Genotypes were linked to individual patients' outcome data and response to chemotherapy. The association between genotype and progression-free survival was assessed by Cox regression analysis adjusting for treatment and clinicopathology. RESULTS: The strongest associations were shown for rs1949733 (ACOX3; P=8.22x10-7), rs1342899 (P=7.72×10(-7)) and rs11158493 (PPP2R5E; P=8.50×10(-7)). In addition, the 52 single nucleotide polymorphisms associated at P<10(-4) included rs438034 (CENPF; P=4.86×10(-6)), previously correlated with cancer progression, and rs2255235 (B2M; P=3.10×10(-5)) and rs2064501 (IL22RA2; P=4.81×10(-5)) which map to B-cell genes. CONCLUSIONS: Our findings provide evidence that genetic variation is a determinant of progression-free survival of patients with chronic lymphocytic leukemia. Specific associations warrant further analyses.
Authors: G Del Poeta; L Maurillo; A Venditti; F Buccisano; A M Epiceno; G Capelli; A Tamburini; G Suppo; A Battaglia; M I Del Principe; B Del Moro; M Masi; S Amadori Journal: Blood Date: 2001-11-01 Impact factor: 22.113
Authors: Maria Chiara Di Bernardo; Dalemari Crowther-Swanepoel; Peter Broderick; Emily Webb; Gabrielle Sellick; Ruth Wild; Kate Sullivan; Jayaram Vijayakrishnan; Yufei Wang; Alan M Pittman; Nicola J Sunter; Andrew G Hall; Martin J S Dyer; Estella Matutes; Claire Dearden; Tryfonia Mainou-Fowler; Graham H Jackson; Geoffrey Summerfield; Robert J Harris; Andrew R Pettitt; Peter Hillmen; David J Allsup; James R Bailey; Guy Pratt; Chris Pepper; Chris Fegan; James M Allan; Daniel Catovsky; Richard S Houlston Journal: Nat Genet Date: 2008-08-31 Impact factor: 38.330
Authors: Barbara E Stranger; Matthew S Forrest; Mark Dunning; Catherine E Ingle; Claude Beazley; Natalie Thorne; Richard Redon; Christine P Bird; Anna de Grassi; Charles Lee; Chris Tyler-Smith; Nigel Carter; Stephen W Scherer; Simon Tavaré; Panagiotis Deloukas; Matthew E Hurles; Emmanouil T Dermitzakis Journal: Science Date: 2007-02-09 Impact factor: 47.728
Authors: James E Hayes; Gosia Trynka; Joseph Vijai; Kenneth Offit; Soumya Raychaudhuri; Robert J Klein Journal: PLoS One Date: 2015-09-30 Impact factor: 3.240
Authors: Lee Admoni-Elisha; Itay Nakdimon; Anna Shteinfer; Tal Prezma; Tasleem Arif; Nir Arbel; Anna Melkov; Ori Zelichov; Itai Levi; Varda Shoshan-Barmatz Journal: PLoS One Date: 2016-04-14 Impact factor: 3.240