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Grant Details

Grant Number: 7R03CA132153-03 Interpret this number
Primary Investigator: Chiu, Brian
Organization: University Of Chicago
Project Title: Risk Factors for Molecularly Defined Subgroups of Lymphoma: a Pooled Analysis
Fiscal Year: 2008
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Abstract

DESCRIPTION (provided by applicant): The chromosomal translocation t(14;18)(q32;q21) is one of the most common chromosomal abnormalities in non-Hodgkin lymphoma (NHL). Although the t(14;18) has important clinical ramifications, its etiologic significance remains to be determined. Two recent population-based case-control studies (one in Iowa/Minnesota and the other in Nebraska) addressed this issue by evaluating potential risk factors for t(14;18)-positive and t(14;18)-negative subgroups of NHL. Findings from these two studies indicate that the causes of t(14;18)-positive NHL differ from those of t(14;18)-negative NHL. However, sample sizes of the Iowa/Minnesota and Nebraska studies limited the precision and detail of effect estimate measures. Therefore, we propose a pooled analysis of existing data from these two studies with similar study design and data collection instruments. The central innovative hypothesis is that risk factors differ for discrete subsets of NHL defined by t(14;18) status. The specific aims are to investigate whether the associations with pesticides, family history of hematopoietic cancer, and solvents differ for t(14;18)-defined subgroups of NHL. A total of 327 cases with data on t(14;18) status and 2,677 population-based controls will be available for the pooled analysis. The t(14;18) was determined by the fluorescence in-situ hybridization (FISH) technique in both the Iowa/Minnesota and Nebraska studies. Subtypes of NHL will be defined by the presence or absence of the t(14;18). Logistic and polytomous regression models will be used to estimate the associations between exposures and risk of t(14;18)-defined subtypes of NHL and to compare odds ratios for t(14;18)-positive NHL with odds ratios for t(14;18)-negative NHL. Hierarchical regression will be used to estimate the risk of t(14;18)-positive or t(14;18)-negative NHL associated with specific pesticide exposure. The results will be significant because they will provide new insights into disease etiology. The long-term objective is to improve our understanding of etiopathogenesis of NHL so that we may ultimately identify risk factors that can be modified to reduce the incidences of NHL in the general population. Because the study population is well-characterized and data on the t(14;18), pesticides, and other exposures have already been collected, the proposed study is extremely cost-effective for addressing the etiology of NHL, one of the most common malignancies in this country. Non-Hodgkin lymphoma (NHL) is the fifth most common cancer in the United States, but the causal factors are largely unknown. Recurring chromosomal abnormalities are a hallmark of NHL. Of the numerous chromosomal abnormalities, the t(14;18) is the most common one. Findings from two recent epidemiologic studies conducted in Iowa/Minnesota and Nebraska suggest that the causes of t(14;18)- positive NHL differ from those of t(14;18)-negative NHL. However, the sample size for the individual studies is not large enough for extensive statistical analysis. To address this issue, we propose a pooled analyses of data from these two studies, resulting a total of 327 cases with data on t(14;18) status and 2,677 population-based controls. The large sample size allows us to evaluate the strength and consistency of the associations between exposures and risk of t(14;18)-defined subgroups of NHL. The long-term objective is to improve our understanding of development of NHL so that we may ultimately identify risk factors that can be modified to reduce the occurrences of NHL in the general population. This project directly responds to the NCI strategic plan for cancer preemption because it can elucidate the etiology of NHL.

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Publications

Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Morton LM, Slager SL, Cerhan JR, Wang SS, Vajdic CM, Skibola CF, Bracci PM, de Sanjosé S, Smedby KE, Chiu BC, Zhang Y, Mbulaiteye SM, Monnereau A, Turner JJ, Clavel J, Adami HO, Chang ET, Glimelius B, Hjalgrim H, Melbye M, Crosignani P, di Lollo S, Miligi L, Nanni O, Ramazzotti V, Rodella S, Costantini AS, Stagnaro E, Tumino R, Vindigni C, Vineis P, Becker N, Benavente Y, Boffetta P, Brennan P, Cocco P, Foretova L, Maynadié M, Nieters A, Staines A, Colt JS, Cozen W, Davis S, de Roos AJ, Hartge P, Rothman N, Severson RK, Holly EA, Call TG, Feldman AL, Habermann TM, Liebow M, Blair A, Cantor KP, Kane EV, Lightfoot T, Roman E, Smith A, Brooks-Wilson A, Connors JM, Gascoyne RD, Spinelli JJ, Armstrong BK, Kricker A, Holford TR, Lan Q, Zheng T, Orsi L, Dal Maso L, Franceschi S, La Vecchia C, Negri E, Serraino D, Bernstein L, Levine A, Friedberg JW, Kelly JL, Berndt SI, Birmann BM, Clarke CA, Flowers CR, Foran JM, Kadin ME, Paltiel O, Weisenburger DD, Linet MS, Sampson JN
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 130-44.
PMID: 25174034
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Medical history, lifestyle, family history, and occupational risk factors for adult acute lymphocytic leukemia: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Skibola CF, Slager SL, Berndt SI, Lightfoot T, Sampson JN, Morton LM, Weisenburger DD
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 125-9.
PMID: 25174033
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Medical history, lifestyle, and occupational risk factors for hairy cell leukemia: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Monnereau A, Slager SL, Hughes AM, Smith A, Glimelius B, Habermann TM, Berndt SI, Staines A, Norman AD, Cerhan JR, Sampson JN, Morton LM, Clavel J
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 115-24.
PMID: 25174032
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Medical history, lifestyle, family history, and occupational risk factors for sporadic Burkitt lymphoma/leukemia: the Interlymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Mbulaiteye SM, Morton LM, Sampson JN, Chang ET, Costas L, de Sanjosé S, Lightfoot T, Kelly J, Friedberg JW, Cozen W, Marcos-Gragera R, Slager SL, Birmann BM, Weisenburger DD
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 106-14.
PMID: 25174031
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Medical history, lifestyle, family history, and occupational risk factors for mycosis fungoides and Sézary syndrome: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Aschebrook-Kilfoy B, Cocco P, La Vecchia C, Chang ET, Vajdic CM, Kadin ME, Spinelli JJ, Morton LM, Kane EV, Sampson JN, Kasten C, Feldman AL, Wang SS, Zhang Y
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 98-105.
PMID: 25174030
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Medical history, lifestyle, family history, and occupational risk factors for lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Vajdic CM, Landgren O, McMaster ML, Slager SL, Brooks-Wilson A, Smith A, Staines A, Dogan A, Ansell SM, Sampson JN, Morton LM, Linet MS
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 87-97.
PMID: 25174029
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Medical history, lifestyle, family history, and occupational risk factors for mantle cell lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Smedby KE, Sampson JN, Turner JJ, Slager SL, Maynadié M, Roman E, Habermann TM, Flowers CR, Berndt SI, Bracci PM, Hjalgrim H, Weisenburger DD, Morton LM
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 76-86.
PMID: 25174028
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Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Wang SS, Flowers CR, Kadin ME, Chang ET, Hughes AM, Ansell SM, Feldman AL, Lightfoot T, Boffetta P, Melbye M, Lan Q, Sampson JN, Morton LM, Zhang Y, Weisenburger DD
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 66-75.
PMID: 25174027
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Medical history, lifestyle, family history, and occupational risk factors for marginal zone lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Bracci PM, Benavente Y, Turner JJ, Paltiel O, Slager SL, Vajdic CM, Norman AD, Cerhan JR, Chiu BC, Becker N, Cocco P, Dogan A, Nieters A, Holly EA, Kane EV, Smedby KE, Maynadié M, Spinelli JJ, Roman E, Glimelius B, Wang SS, Sampson JN, Morton LM, de Sanjosé S
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 52-65.
PMID: 25174026
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Medical history, lifestyle, family history, and occupational risk factors for chronic lymphocytic leukemia/small lymphocytic lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Slager SL, Benavente Y, Blair A, Vermeulen R, Cerhan JR, Costantini AS, Monnereau A, Nieters A, Clavel J, Call TG, Maynadié M, Lan Q, Clarke CA, Lightfoot T, Norman AD, Sampson JN, Casabonne D, Cocco P, de Sanjosé S
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 41-51.
PMID: 25174025
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Medical history, lifestyle, family history, and occupational risk factors for follicular lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Linet MS, Vajdic CM, Morton LM, de Roos AJ, Skibola CF, Boffetta P, Cerhan JR, Flowers CR, de Sanjosé S, Monnereau A, Cocco P, Kelly JL, Smith AG, Weisenburger DD, Clarke CA, Blair A, Bernstein L, Zheng T, Miligi L, Clavel J, Benavente Y, Chiu BC
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 26-40.
PMID: 25174024
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Medical history, lifestyle, family history, and occupational risk factors for diffuse large B-cell lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Cerhan JR, Kricker A, Paltiel O, Flowers CR, Wang SS, Monnereau A, Blair A, Dal Maso L, Kane EV, Nieters A, Foran JM, Miligi L, Clavel J, Bernstein L, Rothman N, Slager SL, Sampson JN, Morton LM, Skibola CF
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 15-25.
PMID: 25174023
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Rationale and Design of the International Lymphoma Epidemiology Consortium (InterLymph) Non-Hodgkin Lymphoma Subtypes Project.
Authors: Morton LM, Sampson JN, Cerhan JR, Turner JJ, Vajdic CM, Wang SS, Smedby KE, de Sanjosé S, Monnereau A, Benavente Y, Bracci PM, Chiu BC, Skibola CF, Zhang Y, Mbulaiteye SM, Spriggs M, Robinson D, Norman AD, Kane EV, Spinelli JJ, Kelly JL, La Vecchia C, Dal Maso L, Maynadié M, Kadin ME, Cocco P, Costantini AS, Clarke CA, Roman E, Miligi L, Colt JS, Berndt SI, Mannetje A, de Roos AJ, Kricker A, Nieters A, Franceschi S, Melbye M, Boffetta P, Clavel J, Linet MS, Weisenburger DD, Slager SL
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 1-14.
PMID: 25174022
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Pesticides, chromosomal aberrations, and non-Hodgkin's lymphoma.
Authors: Chiu BC, Blair A
Source: J Agromedicine, 2009;14(2), p. 250-5.
PMID: 19437285
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The utility of t(14;18) in understanding risk factors for non-Hodgkin lymphoma.
Authors: Chiu BC, Lan Q, Dave BJ, Blair A, Zahm SH, Weisenburger DD
Source: J Natl Cancer Inst Monogr, 2008;null(39), p. 69-73.
PMID: 18648007
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Dietary factors and risk of t(14;18)-defined subgroups of non-Hodgkin lymphoma.
Authors: Chiu BC, Dave BJ, Ward MH, Fought AJ, Hou L, Jain S, Gapstur S, Evens AM, Zahm SH, Blair A, Weisenburger DD
Source: Cancer Causes Control, 2008 Oct;19(8), p. 859-67.
EPub date: 2008 Apr 2.
PMID: 18386141
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