title: Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia.
abstract: Acute lymphoblastic leukemia is the major pediatric cancer in developed countries. To date most association studies of acute lymphoblastic leukemia have been based on the candidate gene approach and have evaluated a restricted number of polymorphisms. Such studies have served to highlight difficulties in conducting statistically and methodologically rigorous investigations into acute lymphoblastic leukemia risk. Recent genome-wide association studies of childhood acute lymphoblastic leukemia have provided robust evidence that common variation at four genetic loci confers a modest increase in risk. The accumulated experience to date and relative lack of success of initial efforts to identify novel acute lymphoblastic leukemia predisposition loci emphasize the need for alternative study designs and methods. The International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium includes 12 research groups in Europe, Asia, the Middle East and the Americas engaged in studying the genetics of acute lymphoblastic leukemia. The initial goal of this consortium is to identify and characterize low-penetrance susceptibility variants for acute lymphoblastic leukemia through association-based analyses. Efforts to develop genome-wide association studies of acute lymphoblastic leukemia, in terms of both sample size and single nucleotide polymorphism coverage, and to increase the number of single nucleotide polymorphisms taken forward to large-scale replication should lead to the identification of additional novel risk variants for acute lymphoblastic leukemia. Ethnic differences in the risk of acute lymphoblastic leukemia are well recognized and thus in assessing the interplay between inherited and non-genetic risk factors, analyses using different population cohorts with different incidence rates are likely to be highly informative. Given that the frequency of many acute lymphoblastic leukemia subgroups is small, identifying differential effects will realistically only be possible through multi-center pooled analyses. Here, we review the rationale for identifying genetic risk variants for acute lymphoblastic leukemia and our proposed strategy for establishing the International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium.
authors: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
authors: Amy L
authors: AL
authors: Sherborne
authors: Kari
authors: K
authors: Hemminki
authors: Rajiv
authors: R
authors: Kumar
authors: Claus R
authors: CR
authors: Bartram
authors: Martin
authors: M
authors: Stanulla
authors: Martin
authors: M
authors: Schrappe
authors: Eleni
authors: E
authors: Petridou
authors: Agnes F
authors: AF
authors: Semsei
authors: Csaba
authors: C
authors: Szalai
authors: Daniel
authors: D
authors: Sinnett
authors: Maja
authors: M
authors: Krajinovic
authors: Jasmine
authors: J
authors: Healy
authors: Marina
authors: M
authors: Lanciotti
authors: Carlo
authors: C
authors: Dufour
authors: Stefania
authors: S
authors: Indaco
authors: Eman A
authors: EA
authors: El-Ghouroury
authors: Ruchchadol
authors: R
authors: Sawangpanich
authors: Suradej
authors: S
authors: Hongeng
authors: Samart
authors: S
authors: Pakakasama
authors: Anna
authors: A
authors: Gonzalez-Neira
authors: Evelia L
authors: EL
authors: Ugarte
authors: Valeria P
authors: VP
authors: Leal
authors: Juan P M
authors: JP
authors: Espinoza
authors: Azza M
authors: AM
authors: Kamel
authors: Gamal T A
authors: GT
authors: Ebid
authors: Eman R
authors: ER
authors: Radwan
authors: Serap
authors: S
authors: Yalin
authors: Erdinc
authors: E
authors: Yalin
authors: Mehmet
authors: M
authors: Berkoz
authors: Jill
authors: J
authors: Simpson
authors: Eve
authors: E
authors: Roman
authors: Tracy
authors: T
authors: Lightfoot
authors: Fay J
authors: FJ
authors: Hosking
authors: Jayaram
authors: J
authors: Vijayakrishnan
authors: Mel
authors: M
authors: Greaves
authors: Richard S
authors: RS
authors: Houlston
mesh_terms: D000483:Alleles; D002648:Child; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007391:International Cooperation; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012106:Research / Q000592:standards / Q000639:trends