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Grant Details

Grant Number: 5R01CA098122-04 Interpret this number
Primary Investigator: Laden, Francine
Organization: Brigham And Women'S Hospital
Project Title: Exposure to Organochlorines, EBV, and the Risk of Nhl
Fiscal Year: 2006
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Abstract

DESCRIPTION (provided by applicant): The worldwide increase in the incidence of non-Hodgkin's lymphoma (NHL) over the past century is largely unexplained. Current epidemiologic evidence suggests a role in the etiology of the disease for organochlorine compounds, such as the pesticide DDT and the industrial chemicals polychlorinated biphenyls (PCBs) and for the Epstein-Barr Virus (EBV). The risks associated with high blood/adipose levels of organochlorines have ranged from two to four-fold. It is well established that EBV plays a causal role in many cases of NHL among patients who are immune suppressed, and the few studies assessing EBV in apparently normal populations have also shown that altered EBV antibody patterns are associated with NHL. Finally, strong statistically significant multiplicative interactions between EBV and organochlorines on the risk of NHL have been reported, with odds ratios as high as 22 for the high PCB/elevated EBV antibodies group compared to the low PCBs/Iow EBV antibodies group. All of the previous studies have been small and need to be replicated in other populations. We propose to utilize two large well-characterized collections of archived blood samples - the Nurses' Health Study, a study of women, and the Physician's Health Study, a study of men - to prospectively address the role of organochlorines and EBV and their potential interaction in the occurrence of NHL. We anticipate 400 incident cases in the combined study population, and we will match each case with two controls who had the same opportunity for development of disease. We will collect pathologic specimens and subtype each case using standard procedures, allowing us to evaluate whether these associations are specific to particular types of NHL. The vast resources of the two cohorts will allow us to assess possible confounders and effect modifiers, including but not limited to, gender and diet. This proposal is led by an experienced team of researchers who have expertise over a range of disciplines that inform this study, Together, we should gain substantial insight into the role of organochlorines and EBV in NHL.

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Publications

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
Authors: Din L. , Sheikh M. , Kosaraju N. , Smedby K.E. , Bernatsky S. , Berndt S.I. , Skibola C.F. , Nieters A. , Wang S. , McKay J.D. , et al. .
Source: Genetic epidemiology, 2019-08-13; , .
EPub date: 2019-08-13.
PMID: 31407831
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A prospective analysis of circulating saturated and monounsaturated fatty acids and risk of non-Hodgkin lymphoma.
Authors: Chiu Y.H. , Bertrand K.A. , Zhang S. , Laden F. , Epstein M.M. , Rosner B.A. , Chiuve S. , Campos H. , Giovannucci E.L. , Chavarro J.E. , et al. .
Source: International journal of cancer, 2018-10-15; 143(8), p. 1914-1922.
EPub date: 2018-08-10.
PMID: 29756258
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Pre-diagnosis plasma immune markers and risk of non-Hodgkin lymphoma in two prospective cohort studies.
Authors: Epstein M.M. , Rosner B. , Breen E.C. , Batista J.L. , Giovannucci E.L. , Magpantay L. , Aster J.C. , Rodig S.J. , Bertrand K.A. , Laden F. , et al. .
Source: Haematologica, 2018 Oct; 103(10), p. 1679-1687.
EPub date: 2018-06-21.
PMID: 29930163
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HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes.
Authors: Wang S.S. , Carrington M. , Berndt S.I. , Slager S.L. , Bracci P.M. , Voutsinas J. , Cerhan J.R. , Smedby K.E. , Hjalgrim H. , Vijai J. , et al. .
Source: Cancer research, 2018-07-15; 78(14), p. 4086-4096.
EPub date: 2018-05-07.
PMID: 29735552
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Dietary fat intake and risk of non-Hodgkin lymphoma in 2 large prospective cohorts.
Authors: Bertrand K.A. , Giovannucci E. , Rosner B.A. , Zhang S.M. , Laden F. , Birmann B.M. .
Source: The American journal of clinical nutrition, 2017 Aug; 106(2), p. 650-656.
EPub date: 2017-06-28.
PMID: 28659300
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Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.
Authors: Law P.J. , Berndt S.I. , Speedy H.E. , Camp N.J. , Sava G.P. , Skibola C.F. , Holroyd A. , Joseph V. , Sunter N.J. , Nieters A. , et al. .
Source: Nature communications, 2017-02-06; 8, p. 14175.
EPub date: 2017-02-06.
PMID: 28165464
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Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma.
Authors: Bernatsky S. , Velásquez García H.A. , Spinelli J.J. , Gaffney P. , Smedby K.E. , Ramsey-Goldman R. , Wang S.S. , Adami H.O. , Albanes D. , Angelucci E. , et al. .
Source: Lupus science & medicine, 2017; 4(1), p. e000187.
EPub date: 2017-11-12.
PMID: 29214033
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Nurses' Health Study Contributions on the Epidemiology of Less Common Cancers: Endometrial, Ovarian, Pancreatic, and Hematologic.
Authors: Birmann B.M. , Barnard M.E. , Bertrand K.A. , Bao Y. , Crous-Bou M. , Wolpin B.M. , De Vivo I. , Tworoger S.S. .
Source: American journal of public health, 2016 Sep; 106(9), p. 1608-15.
EPub date: 2016-07-26.
PMID: 27459458
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Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes.
Authors: Machiela M.J. , Lan Q. , Slager S.L. , Vermeulen R.C. , Teras L.R. , Camp N.J. , Cerhan J.R. , Spinelli J.J. , Wang S.S. , Nieters A. , et al. .
Source: Human molecular genetics, 2016-04-15; 25(8), p. 1663-76.
EPub date: 2016-02-09.
PMID: 27008888
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Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.
Authors: Berndt S.I. , Camp N.J. , Skibola C.F. , Vijai J. , Wang Z. , Gu J. , Nieters A. , Kelly R.S. , Smedby K.E. , Monnereau A. , et al. .
Source: Nature communications, 2016-03-09; 7, p. 10933.
EPub date: 2016-03-09.
PMID: 26956414
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A genome-wide association study of marginal zone lymphoma shows association to the HLA region.
Authors: Vijai J. , Wang Z. , Berndt S.I. , Skibola C.F. , Slager S.L. , de Sanjose S. , Melbye M. , Glimelius B. , Bracci P.M. , Conde L. , et al. .
Source: Nature communications, 2015-01-08; 6, p. 5751.
EPub date: 2015-01-08.
PMID: 25569183
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Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma.
Authors: Cerhan J.R. , Berndt S.I. , Vijai J. , Ghesquières H. , McKay J. , Wang S.S. , Wang Z. , Yeager M. , Conde L. , de Bakker P.I. , et al. .
Source: Nature genetics, 2014 Nov; 46(11), p. 1233-8.
EPub date: 2014-09-28.
PMID: 25261932
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A prospective analysis of body size during childhood, adolescence, and adulthood and risk of non-Hodgkin lymphoma.
Authors: Bertrand K.A. , Giovannucci E. , Zhang S.M. , Laden F. , Rosner B. , Birmann B.M. .
Source: Cancer prevention research (Philadelphia, Pa.), 2013 Aug; 6(8), p. 864-73.
EPub date: 2013-06-26.
PMID: 23803416
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Persistent organic pollutants and type 2 diabetes: a prospective analysis in the nurses' health study and meta-analysis.
Authors: Wu H. , Bertrand K.A. , Choi A.L. , Hu F.B. , Laden F. , Grandjean P. , Sun Q. .
Source: Environmental health perspectives, 2013 Feb; 121(2), p. 153-61.
EPub date: 2012-11-05.
PMID: 23131992
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Sunlight exposure, vitamin D, and risk of non-Hodgkin lymphoma in the Nurses' Health Study.
Authors: Bertrand K.A. , Chang E.T. , Abel G.A. , Zhang S.M. , Spiegelman D. , Qureshi A.A. , Laden F. .
Source: Cancer causes & control : CCC, 2011 Dec; 22(12), p. 1731-41.
EPub date: 2011-10-11.
PMID: 21987081
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A prospective study of Epstein-Barr virus antibodies and risk of non-Hodgkin lymphoma.
Authors: Bertrand K.A. , Birmann B.M. , Chang E.T. , Spiegelman D. , Aster J.C. , Zhang S.M. , Laden F. .
Source: Blood, 2010-11-04; 116(18), p. 3547-53.
EPub date: 2010-07-20.
PMID: 20647565
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Outcomes for lymphoid malignancies in the Nurses' Health Study (NHS) as compared to the Surveillance, Epidemiology and End Results (SEER) Program.
Authors: Abel G.A. , Bertrand K.A. , Earle C.C. , Laden F. .
Source: Hematological oncology, 2010 Sep; 28(3), p. 133-6.
PMID: 19866451
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Plasma organochlorine levels and risk of non-Hodgkin lymphoma in the Nurses' Health Study.
Authors: Laden F. , Bertrand K.A. , Altshul L. , Aster J.C. , Korrick S.A. , Sagiv S.K. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2010 May; 19(5), p. 1381-4.
EPub date: 2010-04-20.
PMID: 20406963
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Persistent organochlorine pesticides in serum and risk of Parkinson disease.
Authors: Weisskopf M.G. , Knekt P. , O'Reilly E.J. , Lyytinen J. , Reunanen A. , Laden F. , Altshul L. , Ascherio A. .
Source: Neurology, 2010-03-30; 74(13), p. 1055-61.
PMID: 20350979
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Plasma organochlorine levels and risk of non-Hodgkin lymphoma in a cohort of men.
Authors: Bertrand K.A. , Spiegelman D. , Aster J.C. , Altshul L.M. , Korrick S.A. , Rodig S.J. , Zhang S.M. , Kurth T. , Laden F. .
Source: Epidemiology (Cambridge, Mass.), 2010 Mar; 21(2), p. 172-80.
PMID: 20087190
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Postmenopausal hormone therapy and stroke: role of time since menopause and age at initiation of hormone therapy.
Authors: Grodstein F. , Manson J.E. , Stampfer M.J. , Rexrode K. .
Source: Archives of internal medicine, 2008-04-28; 168(8), p. 861-6.
PMID: 18443262
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Polychlorinated biphenyl levels in peripheral blood and non-Hodgkin's lymphoma: a report from three cohorts.
Authors: Engel L.S. , Laden F. , Andersen A. , Strickland P.T. , Blair A. , Needham L.L. , Barr D.B. , Wolff M.S. , Helzlsouer K. , Hunter D.J. , et al. .
Source: Cancer research, 2007-06-01; 67(11), p. 5545-52.
PMID: 17545638
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