Document 82ZkV5Z6O58442Ve9pzYb31Ym

The Shanghai Health Study Patsy Clegg Chair, Oversight Committee Shell Chemicals LP June 22, 2005 0 G) c I OzmJ 0 0 0 0 1\J 0 ~ What is the Shanghai Health Study? f A long-term clinical study to investigate the potential causes and development of lympho-hematopoietic diseases (diseases of the lymphoid organs, blood and bone marrow) as related to benzene f> A project of :: Fudan University Medical Center - Shanghai, China [J University of Colorado Health Sciences Center [J Applied Health Sciences -an independent U.S. research firm [J Chinese public health agencies 0 G) c I [J Shanghai hospitals OzmJ 0 0 0 0 1\J 0 01 Path to developing the study: C> Pre-97: ... 97 "ill' Benzene exposure associated with AML NCI published conclusions from China study that: Y AML develops at exposures lower than previously known - no threshold observed Y Benzene is associated with NHL C> 98-00: NCI Methodology criticized ... 01 "ill' Feasibility studies in Shanghai Australian Institute of Petroleum's (AlP) Health Watch Study . . . 01"llljjJ I Y Association with all leukemias, including chronic lymphocytic leukemia Y No association with NHL or multiple myeloma Benzene Health Research Consortium formed to: 0 G) Y do a study to test conclusions c I OzmJ Y address questions of disease progression and biomarkers 0 0 0 0 1\J 0 (j) The Shanghai Health Study is 3 studies 1. Case Control Study Traditional, prospective epidemiology study to determine risk of AML, NHL among benzene exposed workers - 450 AML and 450 NHL patients into study 2. Disease Progression Study Prospective study on relationship of non-cancer bone marrow disease and benzene induced AML 3. Molecular Epidemiology Study 0 G) Prospective study seeking to establish quantitative c I OzmJ relationship between exposure and effect 0 0 0 0 1\J 0 -..J The Shanghai Health Study 1. Case Control Study - Update Traditional, prospective epidemiology study to determine risk of AML, NHL among benzene exposed workers - 450 AML and 450 NHL patients into study As of YE04: );. Disease recruitment on track 0 G) c I OzmJ 0 0 0 0 1\J 0 (X) The Shanghai Health Study 2. Disease Progression Study - Update Prospective study on relationship of non-cancer bone marrow disease and benzene induced AML y Unique profile of MDS (myelodysplastic syndrome) identified in highbenzene exposed workers ~ Characterized as BIMDS (benzene-induced myelodysplastic syndrome) ~ MDS subtype profile established ~ Suggests that immune parameters have a much larger influence than originally thought 0 ~ Both BIMDS and MDS-subtyping will appear as manuscripts G) c I OzmJ 0 0 0 0 1\J 0c.o The Shanghai Health Study 3. Molecular Epidemiology Study - Update Prospective study seeking to establish quantitative relationship between exposure and effect "ir Have successfully recruited several factories "ir Records for over 1000 cases have been abstracted 0 G) c I OzmJ 0 0 0 0 1...\..J. 0 Uniqueness ofShanghai Study C> Prospective research :: Patients at participating hospitals suspected of having a lymphoid, blood or bone marrow disease are referred to the SHS :: Patients, environmental exposures and family histories are recorded :: Patient disease progression followed at supporting hospitals 0 G) c I OzmJ 0 0 0 0 1......\....J.. Uniqueness ofShanghai Study f> Study examines primary diagnostic and medical data in real time C> State-owned databases document worker exposure readings from some jobs/locations 0 G) c I OzmJ 0 0 0 0 1...\..J. 1\J Why Shanghai? C) Benzene related health effects are #2 in reported chronic occupational health hazards in China in 2001 (source: Ministry ofPublic Health) C) Large range of exposure levels from a variety of occupational sources C) Regulatory authorities interest in improving 8 benzene exposure regulation and ~~ enforcement z 0 0 0 0 1...\..J. (...) Quality, Independent Science f> All protocols reviewed and approved by external Institutional Review Boards (IRS's) tJ Govern use of human subjects :: U.S. and China independently f> Shanghai Health Study independent review panels tJ International Ethics Review Panel 4 members - 1 each from China & Europe, and 2 US :: International Scientific Review Panel 12 members 6 scientific disciplines 0 tJ Involved during entire project G) c I OzmJ 0 0 0 0 1...\..J. ~ Benzene Health Research Consortium Sponsoring Companies Y BP y ChevronTexaco y ConocoPhillips y ExxonMobil y Shell Chemical LP y Marathon/Ashland providing additional support 0 G) c I OzmJ 0 0 0 0 1...\..J. 01 Benzene Health Research Consortium Organization Oversight Committee ll Technical/Budget Communication Scientific Review Panel Ethics Review Panel 0 G) c API Administrative Support I OzmJ 0 0 0 0 1...\..J. (j) Shanghai Health Study Study Participants Principal Investigators: Dr. Richard Irons, U of Colorado Health Sciences Center Dr. Otto Wong, Applied Health Sciences Dr. Fu Hua, Fudan University Collaborators: ExxonMobil Biomedical Sciences Chinese Participants: Fudan University School of Medicine 31 area Shanghai hospitals Shanghai Municipal Center for Disease Prevention Shanghai Hematology Society Shanghai Pathology Institute for Public Health Supervision Shanghai Public Health Bureau 0 G) c Internal Review Boards U of Colorado, Fudan University, AHS I OzmJ 0 0 0 0 1...\..J. -..J Shanghai Health Study Study Time Line Aug 01 Consortium Formed 3/4Q01 Protocols Reviewed 2002 JCML Lab constructed, equipped at Fudan; technicians trained 3Q03 Began accruing cases Aug 03 First Annual Meeting 4Q03 Opening Ceremony in Shanghai Aug 04 Second Annual Meeting Oct 04 International Benzene Symposium 0 G) Nov OS Third Annual Meeting c I OzmJ 2007/8 Report/Publications in scientific journals 0 0 0 0 1...\..J. (X) ~ ;:s ~ ;S ~ \:5 ~ ~ \:5 ~ ~ \:5 ~ Vl -1--1 ::E: Vl \.0 u0 N ~ ::E: \.0 N ~ ........, Q) en "'0 "cce'-0n c::o:J :::J LL CGU BEN0000219 Shanghai Health Study Summary C> Opportunity to obtain a better understanding of the mechanism of benzene induced disease in humans. <> Potential significant impact on benzene risk assessment. <> Highest Quality of Science: employs state-of-the-art biological and epidemiological sc1ence represents sound product stewardship exemplifies best practices in research ethics depends upon partnership of industry, governments, 0 G) academia and public lc OzmJ 0 0 0 0 1\J 1\J 0 Slide Notes Slide2: NCI Study: Benzene associated with AML and Non Hodgkin's Lymphoma (NHL) -first significant association with a non-AML cancer No threshold observed (effects observed in lowest exposure group of 10 ppm or less) Australian Health Watch Australian Institute of Petroleum's (AlP) Health Watch Study: Case-control study published in 2001 Strong association with all leukemias, including chronic lymphocytic leukemia No association with NHL or multiple myeloma Low exposures (<1 -2 ppm) with no apparent threshold Significant methodological problems Slide3: NCI Study: Benzene associated with AML and Non Hodgkin's Lymphoma (NHL) -first significant association with a non-AML cancer No threshold observed (effects observed in lowest exposure group of 10 ppm or less) 0 G) c I OzmJ 0 0 0 0 1\J 1\J Slide Notes Australian Health Watch Australian Institute of Petroleum's (AlP) Health Watch Study: Case-control study published in 2001 Strong association with all leukemias, including chronic lymphocytic leukemia No association with NHL or multiple myeloma Low exposures (<1 -2 ppm) with no apparent threshold Significant methodological problems Slide4: Feasibility studies in Shanghai in 1999 documented High exposure levels; good records Sufficient numbers of cases of disease for valid study Willing scientific collaborators in Shanghai 1. Traditional epidemiology study to determine risk of AML, NHL among benzene exposed workers Should identify other causal factors for NHL besides benzene exposure Estimate 4 years to obtain 450 new AML and 450 new NHL cases 0 G) Improved Exposure Assessment based on historical and concurrent workplace monitoring and questionnaire c I OzmJ 0 0 0 0 1\J 1\J 1\J Slide Notes 2. Prospective study on relationship of non-cancer bone marrow disease and benzene induced AML Is benzene induced AML different from spontaneous AML? Are there unique markers for benzene induced AML? Questionnaire, interviews, review work histories; examine blood, breath, urine, evaluation of biomarkers of exposure 3. Prospective study to establish quantitative relationship between exposure and effect Do benzene exposures as low as 7 ppm (as in NCI study) cause blood effects? Is there an association of blood effects and genetics Do biomarkers of exposure accurately reflect workplace exposures? Healthy workers exposed to varying levels of benzene will participate; extensive lab work including genetic tests will be conducted SlideS: Feasibility studies in Shanghai in 1999 documented High exposure levels; good records Sufficient numbers of cases of disease for valid study 0 G) Willing scientific collaborators in Shanghai c I OzmJ 0 0 0 0 1\J 1\J (...) Slide Notes 1. Traditional epidemiology study to determine risk of AML, NHL among benzene exposed workers Should identify other causal factors for NHL besides benzene exposure Estimate 4 years to obtain 450 new AML and 450 new NHL cases Improved Exposure Assessment based on historical and concurrent workplace monitoring and questionnaire 2. Prospective study on relationship of non-cancer bone marrow disease and benzene induced AML Is benzene induced AML different from spontaneous AML? Are there unique markers for benzene induced AML? Questionnaire, interviews, review work histories; examine blood, breath, urine, evaluation of biomarkers of exposure 3. Prospective study to establish quantitative relationship between exposure and effect Do benzene exposures as low as 7 ppm (as in NCI study) cause blood effects? Is there an association of blood effects and genetics Do biomarkers of exposure accurately reflect workplace exposures? Healthy workers exposed to varying levels of benzene will participate; extensive lab work including genetic tests will be conducted 0 G) c I OzmJ 0 0 0 0 1\J 1\J ~ Slide Notes SlideS: Feasibility studies in Shanghai in 1999 documented High exposure levels; good records Sufficient numbers of cases of disease for valid study Willing scientific collaborators in Shanghai 1. Traditional epidemiology study to determine risk of AML, NHL among benzene exposed workers Should identify other causal factors for NHL besides benzene exposure Estimate 4 years to obtain 450 new AML and 450 new NHL cases Improved Exposure Assessment based on historical and concurrent workplace monitoring and questionnaire 2. Prospective study on relationship of non-cancer bone marrow disease and benzene induced AML Is benzene induced AML different from spontaneous AML? Are there unique markers for benzene induced AML? Questionnaire, interviews, review work histories; examine blood, breath, urine, evaluation of biomarkers of exposure 3. Prospective study to establish quantitative relationship between exposure and effect Do benzene exposures as low as 7 ppm (as in NCI study) cause blood effects? Is there an association of blood effects and genetics 0 G) Do biomarkers of exposure accurately reflect workplace exposures? c I OzmJ 0 0 0 0 1\J 1\J 01 Slide Notes Healthy workers exposed to varying levels of benzene will participate; extensive lab work including genetic tests will be conducted Slide7: Feasibility studies in Shanghai in 1999 documented High exposure levels; good records Sufficient numbers of cases of disease for valid study Willing scientific collaborators in Shanghai 1. Traditional epidemiology study to determine risk of AML, NHL among benzene exposed workers Should identify other causal factors for NHL besides benzene exposure Estimate 4 years to obtain 450 new AML and 450 new NHL cases Improved Exposure Assessment based on historical and concurrent workplace monitoring and questionnaire 2. Prospective study on relationship of non-cancer bone marrow disease and benzene induced AML Is benzene induced AML different from spontaneous AML? Are there unique markers for benzene induced AML? 0 G) Questionnaire, interviews, review work histories; examine blood, breath, urine, evaluation of biomarkers of exposure c I OzmJ 0 0 0 0 1\J 1\J (j) Slide Notes 3. Prospective study to establish quantitative relationship between exposure and effect Do benzene exposures as low as 7 ppm (as in NCI study) cause blood effects? Is there an association of blood effects and genetics Do biomarkers of exposure accurately reflect workplace exposures? Healthy workers exposed to varying levels of benzene will participate; extensive lab work including genetic tests will be conducted SlideS: Feasibility studies in Shanghai in 1999 documented High exposure levels; good records Sufficient numbers of cases of disease for valid study Willing scientific collaborators in Shanghai 1. Traditional epidemiology study to determine risk of AML, NHL among benzene exposed workers Should identify other causal factors for NHL besides benzene exposure Estimate 4 years to obtain 450 new AML and 450 new NHL cases 0 G) Improved Exposure Assessment based on historical and concurrent workplace monitoring and questionnaire c I OzmJ 0 0 0 0 1\J 1\J -..J Slide Notes 2. Prospective study on relationship of non-cancer bone marrow disease and benzene induced AML Is benzene induced AML different from spontaneous AML? Are there unique markers for benzene induced AML? Questionnaire, interviews, review work histories; examine blood, breath, urine, evaluation of biomarkers of exposure 3. Prospective study to establish quantitative relationship between exposure and effect Do benzene exposures as low as 7 ppm (as in NCI study) cause blood effects? Is there an association of blood effects and genetics Do biomarkers of exposure accurately reflect workplace exposures? Healthy workers exposed to varying levels of benzene will participate; extensive lab work including genetic tests will be conducted Slide9: Feasibility studies in Shanghai in 1999 documented High exposure levels; good records Sufficient numbers of cases of disease for valid study 0 G) Willing scientific collaborators in Shanghai c I OzmJ 0 0 0 0 1\J 1\J (X) Slide Notes 1. Traditional epidemiology study to determine risk of AML, NHL among benzene exposed workers Should identify other causal factors for NHL besides benzene exposure Estimate 4 years to obtain 450 new AML and 450 new NHL cases Improved Exposure Assessment based on historical and concurrent workplace monitoring and questionnaire 2. Prospective study on relationship of non-cancer bone marrow disease and benzene induced AML Is benzene induced AML different from spontaneous AML? Are there unique markers for benzene induced AML? Questionnaire, interviews, review work histories; examine blood, breath, urine, evaluation of biomarkers of exposure 3. Prospective study to establish quantitative relationship between exposure and effect Do benzene exposures as low as 7 ppm (as in NCI study) cause blood effects? Is there an association of blood effects and genetics Do biomarkers of exposure accurately reflect workplace exposures? Healthy workers exposed to varying levels of benzene will participate; extensive lab work including genetic tests will be conducted 0 G) c I OzmJ 0 0 0 0 1\J 1c.\oJ Slide Notes Slide 10: Feasibility studies in Shanghai in 1999 documented High exposure levels; good records Sufficient numbers of cases of disease for valid study Willing scientific collaborators in Shanghai 1. Traditional epidemiology study to determine risk of AML, NHL among benzene exposed workers Should identify other causal factors for NHL besides benzene exposure Estimate 4 years to obtain 450 new AML and 450 new NHL cases Improved Exposure Assessment based on historical and concurrent workplace monitoring and questionnaire 2. Prospective study on relationship of non-cancer bone marrow disease and benzene induced AML Is benzene induced AML different from spontaneous AML? Are there unique markers for benzene induced AML? Questionnaire, interviews, review work histories; examine blood, breath, urine, evaluation of biomarkers of exposure 3. Prospective study to establish quantitative relationship between exposure and effect Do benzene exposures as low as 7 ppm (as in NCI study) cause blood effects? Is there an association of blood effects and genetics 0 G) Do biomarkers of exposure accurately reflect workplace exposures? c I OzmJ 0 0 0 0 1\J (...) 0 Slide Notes Healthy workers exposed to varying levels of benzene will participate; extensive lab work including genetic tests will be conducted Slide 11: Feasibility studies in Shanghai in 1999 documented High exposure levels; good records Sufficient numbers of cases of disease for valid study Willing scientific collaborators in Shanghai 1. Traditional epidemiology study to determine risk of AML, NHL among benzene exposed workers Should identify other causal factors for NHL besides benzene exposure Estimate 4 years to obtain 450 new AML and 450 new NHL cases Improved Exposure Assessment based on historical and concurrent workplace monitoring and questionnaire 2. Prospective study on relationship of non-cancer bone marrow disease and benzene induced AML Is benzene induced AML different from spontaneous AML? Are there unique markers for benzene induced AML? 0 G) Questionnaire, interviews, review work histories; examine blood, breath, urine, evaluation of biomarkers of exposure c I OzmJ 0 0 0 0 1\J (...) Slide Notes 3. Prospective study to establish quantitative relationship between exposure and effect Do benzene exposures as low as 7 ppm (as in NCI study) cause blood effects? Is there an association of blood effects and genetics Do biomarkers of exposure accurately reflect workplace exposures? Healthy workers exposed to varying levels of benzene will participate; extensive lab work including genetic tests will be conducted Slide 13: General Toxicology and Biochemistry Dr. Jerry M. Rice, ( Chair), IARC Dr. Helmut Greim, Technical University of Munich Epidemiology Dr. Nancy Mueller (Vice Chair), Harvard School of Public Health Dr. Harvey Checkoway, University of Washington Statistics Dr. Howard Rockette, University of Pittsburgh Industrial Hygiene Dr. John Cherrie, Aberdeen University, lnst. Of Occ. Medicine 0 G) Dr. Robert F. Herrick, Harvard School of Public Health c I OzmJ 0 0 0 0 1\J (...) 1\J Slide Notes Hematology Dr. Richard Larson, University of Chicago Medical School Dr. Mark Minden, University of Toronto Genetic Toxicology Dr. Li Guilan, Chinese Academy of Preventive Medicine Dr. Richard Albertini, University of Vermont, College of Medicine Ethics Review Panel Dr. Baruch Brody (Chair), Baylor College of Medicine Dr. XuZong-Liang, Fudan University 0 G) c I OzmJ 0 0 0 0 1\J (...) (...)