Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia

Amy L Sherborne; Kari Hemminki; Rajiv Kumar; Claus R Bartram; Martin Stanulla; Martin Schrappe; Eleni Petridou; Agnes F Semsei; Csaba Szalai; Daniel Sinnett; Maja Krajinovic; Jasmine Healy; Marina Lanciotti; Carlo Dufour; Stefania Indaco; Eman A El-Ghouroury; Ruchchadol Sawangpanich; Suradej Hongeng; Samart Pakakasama; Anna Gonzalez-Neira; Evelia L Ugarte; Valeria P Leal; Juan P M Espinoza; Azza M Kamel; Gamal T A Ebid; Eman R Radwan; Serap Yalin; Erdinc Yalin; Mehmet Berkoz; Jill Simpson; Eve Roman; Tracy Lightfoot; Fay J Hosking; Jayaram Vijayakrishnan; Mel Greaves; Richard S Houlston

doi:10.3324/haematol.2011.040121

Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia

Amy L Sherborne, Kari Hemminki, Rajiv Kumar, Claus R Bartram, Martin Stanulla, Martin Schrappe, Eleni Petridou, Agnes F Semsei, Csaba Szalai, Daniel Sinnett, Maja Krajinovic, Jasmine Healy, Marina Lanciotti, Carlo Dufour, Stefania Indaco, Eman A El-Ghouroury, Ruchchadol Sawangpanich, Suradej Hongeng, Samart Pakakasama, Anna Gonzalez-NeiraEvelia L Ugarte, Valeria P Leal, Juan P M Espinoza, Azza M Kamel, Gamal T A Ebid, Eman R Radwan, Serap Yalin, Erdinc Yalin, Mehmet Berkoz, Jill Simpson, Eve Roman, Tracy Lightfoot, Fay J Hosking, Jayaram Vijayakrishnan, Mel Greaves, Richard S Houlston

Health Sciences

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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.

Original language	English
Pages (from-to)	1049-54
Number of pages	6
Journal	Haematologica-The hematology journal
Volume	96
Issue number	7
DOIs	https://doi.org/10.3324/haematol.2011.040121
Publication status	Published - Jul 2011

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Sherborne, A. L., Hemminki, K., Kumar, R., Bartram, C. R., Stanulla, M., Schrappe, M., Petridou, E., Semsei, A. F., Szalai, C., Sinnett, D., Krajinovic, M., Healy, J., Lanciotti, M., Dufour, C., Indaco, S., El-Ghouroury, E. A., Sawangpanich, R., Hongeng, S., Pakakasama, S., ... Houlston, R. S. (2011). Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia. Haematologica-The hematology journal, 96(7), 1049-54. https://doi.org/10.3324/haematol.2011.040121

@article{42d32f6103ca4b7390941422b8b65af8,

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.",

author = "Sherborne, {Amy L} and Kari Hemminki and Rajiv Kumar and Bartram, {Claus R} and Martin Stanulla and Martin Schrappe and Eleni Petridou and Semsei, {Agnes F} and Csaba Szalai and Daniel Sinnett and Maja Krajinovic and Jasmine Healy and Marina Lanciotti and Carlo Dufour and Stefania Indaco and El-Ghouroury, {Eman A} and Ruchchadol Sawangpanich and Suradej Hongeng and Samart Pakakasama and Anna Gonzalez-Neira and Ugarte, {Evelia L} and Leal, {Valeria P} and Espinoza, {Juan P M} and Kamel, {Azza M} and Ebid, {Gamal T A} and Radwan, {Eman R} and Serap Yalin and Erdinc Yalin and Mehmet Berkoz and Jill Simpson and Eve Roman and Tracy Lightfoot and Hosking, {Fay J} and Jayaram Vijayakrishnan and Mel Greaves and Houlston, {Richard S}",

year = "2011",

month = jul,

doi = "10.3324/haematol.2011.040121",

language = "English",

volume = "96",

pages = "1049--54",

journal = "Haematologica-The hematology journal",

publisher = "Ferrata Storti Foundation",

number = "7",

}

Sherborne, AL, Hemminki, K, Kumar, R, Bartram, CR, Stanulla, M, Schrappe, M, Petridou, E, Semsei, AF, Szalai, C, Sinnett, D, Krajinovic, M, Healy, J, Lanciotti, M, Dufour, C, Indaco, S, El-Ghouroury, EA, Sawangpanich, R, Hongeng, S, Pakakasama, S, Gonzalez-Neira, A, Ugarte, EL, Leal, VP, Espinoza, JPM, Kamel, AM, Ebid, GTA, Radwan, ER, Yalin, S, Yalin, E, Berkoz, M, Simpson, J , Roman, E , Lightfoot, T, Hosking, FJ, Vijayakrishnan, J, Greaves, M & Houlston, RS 2011, 'Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia', Haematologica-The hematology journal, vol. 96, no. 7, pp. 1049-54. https://doi.org/10.3324/haematol.2011.040121

TY - JOUR

T1 - Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia

AU - Sherborne, Amy L

AU - Hemminki, Kari

AU - Kumar, Rajiv

AU - Bartram, Claus R

AU - Stanulla, Martin

AU - Schrappe, Martin

AU - Petridou, Eleni

AU - Semsei, Agnes F

AU - Szalai, Csaba

AU - Sinnett, Daniel

AU - Krajinovic, Maja

AU - Healy, Jasmine

AU - Lanciotti, Marina

AU - Dufour, Carlo

AU - Indaco, Stefania

AU - El-Ghouroury, Eman A

AU - Sawangpanich, Ruchchadol

AU - Hongeng, Suradej

AU - Pakakasama, Samart

AU - Gonzalez-Neira, Anna

AU - Ugarte, Evelia L

AU - Leal, Valeria P

AU - Espinoza, Juan P M

AU - Kamel, Azza M

AU - Ebid, Gamal T A

AU - Radwan, Eman R

AU - Yalin, Serap

AU - Yalin, Erdinc

AU - Berkoz, Mehmet

AU - Simpson, Jill

AU - Roman, Eve

AU - Lightfoot, Tracy

AU - Hosking, Fay J

AU - Vijayakrishnan, Jayaram

AU - Greaves, Mel

AU - Houlston, Richard S

PY - 2011/7

Y1 - 2011/7

N2 - 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.

AB - 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.

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DO - 10.3324/haematol.2011.040121

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JO - Haematologica-The hematology journal

JF - Haematologica-The hematology journal

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ER -

Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia

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