Chronic Disease Epidemiology Group
Risk Factors for Chronic Disease
Dale Sandler, Ph.D.
Chief, Epidemiology Branch and Principal Investigator
The Chronic Disease Epidemiology Group studies a wide range of chronic diseases and conditions. Current work takes advantage of large prospective cohort studies (described below) developed to study the impact of environmental and lifestyle exposures on population health. These cohorts allow for both hypothesis driven and opportunistic research, enabling the group to explore outcomes not envisioned when the cohorts were designed, and foster translational and cross-disciplinary research.
The group includes four Staff Scientists and a part-time Associate Investigator working under an Interagency Personnel Act Agreement who serve as lead investigators for research involving the Epidemiology Branch cohorts and conduct related research. Dr. Lisa DeRoo is Staff Scientist for the Sister Study and carries out research on early life and lifestyle factors related to breast cancer and other outcomes. Dr. Jane Hoppin is co-PI of the Agricultural Health Study and conducts research on agricultural exposures and respiratory symptoms and disease. Dr. Freya Kamel leads research on Parkinson’s disease and other neurological outcomes in the Agricultural Health Study as well as studies of genetic and environmental contributors to amyotrophic lateral sclerosis (ALS). Dr. Richard Kwok has helped to develop the Gulf Long-term Follow-up Study (GuLF STUDY) and serves as Co-PI for the cohort. Dr. Lawrence Engel, Associate Professor of Epidemiology at the University of North Carolina School of Public Health, serves, along with Drs. Sandler and Kwok, as Co-PI of the GuLF STUDY.
The Chronic Disease Epidemiology Group is headed by Dr. Dale Sandler, who also is Chief of the Epidemiology Branch in the Division of Intramural Research at NIEHS. Sandler is adjunct professor of Epidemiology at the University of North Carolina at Chapel Hill, past editor of the journal, Epidemiology, and a past president of the American College of Epidemiology. Sandler has authored more than 230 articles in peer-reviewed journals. She received an M.P.H. from Yale University in 1975 and a Ph.D. in Epidemiology from The Johns Hopkins University in 1979.
Sandler’s research includes ongoing analyses of earlier case-control studies of risk factors for chronic kidney disease and leukemia and studies of occupational and residential exposure to radon. Recent work focuses on exposure across the lifespan in relation to risk for breast cancer and other health outcomes in women and potential mental and physical health effects associated with exposure to oil, dispersants and stress following the Deepwater Horizon oil-spill disaster in the Gulf of Mexico in April 2010.
In 1990, Sandler partnered with the National Cancer Institute to develop the Agricultural Health Study, a prospective study of licensed pesticide applicators and their spouses. While initially conceived as a logical next step in understanding the contributions of pesticides to cancer risk, Sandler expanded the focus to include non-cancer outcomes plausibly linked to agricultural exposures. With Drs. Hoppin and Kamel, her group has added comprehensive studies of neurobehavioral function, Parkinson’s disease, and lung function. Sandler has used AHS data to study pesticides in relation to risk for diabetes and thyroid disease, and has initiated studies of chronic kidney disease, including linking the cohort to the US Renal Data System to study incidence of End Stage Renal Disease (ESRD).
Sandler is Principal Investigator of The Sister Study, a prospective cohort of over 50,000 women with enhanced risk for breast cancer due to having had a sister who was diagnosed with disease. Now that more than 2,000 incident breast cancers have occurred in the cohort, Sandler’s group is studying early life, reproductive, hormonal, environmental and genetic factors related to breast cancer risk. The richness of this resource allows the group to consider the possibility that environmental factors may contribute indirectly to diseases later in life through their effects on growth and development and reproductive health, and to specifically consider the impact of timing of exposures in relation to risk. The group has begun to explore a wide range of potential genetic biomarkers in relation to breast cancer risk, including telomere length, candidate SNPs previously identified from breast cancer genome-wide association studies (GWAS), and global and gene-specific methylation in collaborative studies.
A related effort, The Two Sister Study, in collaboration with Dr. Clarice Weinberg in the NIEHS Biostatistics Branch, is a family-based study of genetic and environmental risk factors for young onset breast cancer. The young-onset sisters added though this effort, together with newly diagnosed cases over the course of the Sister Study, provide a unique survivor cohort for studies of the genetic and environmental factors that contribute along with treatment to healthy survival following breast cancer diagnosis.
With Drs. Richard Kwok and Lawrence Engel, Sandler initiated a multi-stage cohort study, The GuLF STUDY, of persons who were involved in some aspect of oil spill clean-up following the April 2010 Deepwater Horizon disaster in the Gulf of Mexico. Nearly 33,000 persons enrolled between March 2011 and March 2013 by completing a comprehensive telephone interview about their oil spill work experience, current physical and mental health, and health at time of the oil spill. A nested subcohort of 11,200 persons from Gulf states completed home visits that included additional questionnaires, collection of biological and environmental samples, and measurement of lung function and blood pressure. Follow-up includes record linkage and telephone interviews. Outcomes of interest include respiratory and neurological function as well as general physical and mental health symptoms.
- The GuLF STUDY - assesses potential short and long term health effects of the oil spill following the Deepwater Horizon disaster in the Gulf of Mexico in April 2010.
- The Agricultural Health Study - a prospective study of the health of licensed pesticide applicators and their spouses.
- The Sister Study - a prospective study of 50,000 sisters of women who have had breast cancer designed to identify environmental and genetic causes of breast cancer and other diseases in women.
- The Agricultural Health Study (AHS):
Main study website: www.aghealth.org .
The AHS explores a wide range of health outcomes among licensed pesticide applicators, their spouses and children potentially exposed to pesticides and other agricultural hazards. The study includes nearly 5,000 commercial pesticide applicators from Iowa, 52,000 private pesticide applicators, mostly farmers, from Iowa and North Carolina and 32,000 spouses of private applicators who have been followed since enrollment in 1993–1997.
Add-on and nested AHS studies coordinated or facilitated by NIEHS include:
- African-American Farmers and Farm Workers Supplement - Approximately 1,100 African-American farmers and farm workers from eastern North Carolina recruited through churches in four counties and followed for mortality and cancer incidence. In 1999, a questionnaire and blood sample was collected from men in this group to study links between DDE and steroid hormones and markers of immune function.
- Farming and Movement Evaluation (FAME) Study - A nested case-control study of the relationship between Parkinson's disease and exposure to pesticides, other neurotoxicants and soil pathogens, funded in large part by an extramural grant to Dr. Carolyn Tanner at the Parkinson’s Institute. This study, led by Freya Kamel, also examines the connection between the illness and lifestyle factors, skin melanin and polymorphisms in genes involved in xenobiotic metabolism, dopaminergic neurotransmission or xenobiotic-specific membrane transport.
- AHS Neurobehavioral Study - An extramurally-funded cross-sectional study (PI: Frederic Gerr, Ph.D., University of Iowa) involving tests of neurobehavioral and neurological function conducted with 800 AHS cohort members selected based on history of use of organophosphate pesticides. The study, with NIEHS contributions of Jane Hoppin and Freya Kamel, includes questionnaires, clinical measures, and biological samples.
- AHS Lung Health Study - An in-depth investigation of the impact of genetic factors, pesticides and other life-long agricultural exposures on pulmonary function and respiratory health led by Jane Hoppin and Stephanie London and funded through the American Recovery and Reinvestment Act of 2009 (ARRA). This on-going study includes in-home assessment of pulmonary function and collection of dust samples, biologic samples, and additional questionnaire data.
To request AHS data or propose collaborative research see www.aghealthstars.com
- Chronic Renal Disease Study:
Risk factors for chronic renal disease were studied using 548 hospital cases and 514 community controls from four medical centers in North Carolina. Telephone interviews obtained information on past use of analgesic medications, occupational and environmental exposures, lifestyle factors and medical history.
- Czech Uranium Miners Study:
Cancer incidence related to radon exposure was studied in a cohort of over 16,000 underground uranium miners from the Czech Republic followed from 1977–1996.
- GuLF STUDY ("/Rhythmyx/assembler/render?sys_contentid=6846&sys_revision=20&sys_variantid=639&sys_context=0&sys_authtype=0&sys_siteid=&sys_folderid=" sys_dependentvariantid="639" sys_dependentid="6846" inlinetype="rxhyperlink" rxinlineslot="103" sys_dependentid="6846" sys_siteid="" sys_folderid=""):
Main study website: www.gulfstudy.nih.gov
The Gulf Long-term Follow-up Study (GuLF STUDY) is investigating potential health effects associated with clean-up activities following the 2010 Deepwater Horizon disaster in the Gulf of Mexico. Nearly 33,000 persons who performed oil-spill clean-up-related work, supported the clean-up effort, or received safety training but did not work enrolled in the study between March 2011 and March 2013 by completing comprehensive telephone questionnaires about work experiences and health. Nearly 11,200 persons from Gulf states completed home exams that included additional questionnaires, collection of biological and environmental samples, and measurement of lung function and blood pressure.
- The Sister Study ("/Rhythmyx/assembler/render?sys_contentid=36268&sys_revision=2&sys_variantid=639&sys_context=0&sys_authtype=0&sys_siteid=&sys_folderid=" sys_dependentvariantid="639" sys_dependentid="36268" inlinetype="rxhyperlink" rxinlineslot="103" sys_dependentid="36268" sys_siteid="" sys_folderid=""):
Main study website: www.sisterstudy.niehs.nih.gov .
The Sister Study is prospectively examining environmental and familial risk factors for breast cancer and other diseases in a cohort of 50,000 sisters of women who have had breast cancer. Breast cancer-free participants aged 35-74 from across the U.S. and Puerto Rico who had a sister diagnosed with breast cancer enrolled from 2003-2009 by providing questionnaire data about life-time exposures and completing home exams including collection of biological samples. Participants are being followed with brief annual updates and periodic comprehensive questionnaires. As of May 2013, more than 2,000 breast cancers were diagnosed in the cohort.
Related efforts include the Two Sister Study, a family-based study of genetic and environmental risk factors for young-onset breast cancer, and a study in partnership with the CDC of quality of life and other factors associated with breast cancer diagnosis.
For Sister Study questionnaires and information on requesting data or proposing collaborative studies, see www.sisterstudystars.com .
- Sandler DP, Smith JC, Weinberg CR, Buckalew VM, Dennis V, Blythe W, Burgess WP. Analgesic use and chronic renal disease. N Engl J Med 320: 1238-1243, 1989.[Abstract]
- Sandler DP, Shore DL, Anderson JR, Davey FR, Silver RT, Aisner J, Canellos GP, Weiss RB, Trump DL, Arthur D, Wurster-Hill D, McIntyre OR, Bloomfield CD. Cigarette smoking and risk of acute leukemia: Associations with morphology and cytogenetic abnormalities in bone marrow. J Natl Cancer Inst 85: 1994-2003, 1993.[Abstract]
- Rericha V, Kulich M, Rericha R, Shore DL, Sandler DP. Incidence of leukemia and other lymphatic and haematopoietic neoplasms in Czech uranium miners: A case-cohort study. Environ Health Perspect 114: 818-822, 2006.[Abstract]
- Sandler DP, Weinberg CR, Shore DL, Archer VE, Bishop Stone M, Lyon JL, Rothney-Kozlak L, Shepherd M, Stolwijk JAJ. Indoor radon and lung cancer risk in Connecticut and Utah. J Tox Env Health Part A 69: 633-54, 2006.[Abstract]
- Saldana TM, Basso O, Hoppin HA, Baird DD, Knott C, Blair A, Alavanja MCR, Sandler DP. Pesticide exposure and gestational diabetes in the Agricultural Health Study. Diabetes Care 30: 529-34, 2007.[Abstract]
- Montgomery MP, Kamel F, Saldana TM, Alavanja MCR, Sandler DP. Incident diabetes and pesticide exposure among licensed pesticide applicators: Agricultural Health Study 1993 - 2003. American journal of epidemiology 167(10):1235-1246, 2008.[Abstract]
- Parks CG, Miller DB, McCanlies EC, Cawthon RM, Andrew ME, DeRoo LA, Sandler DP. Telomere length, current perceived stress, and urinary stress hormones in women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 18(2):551-560,2009.[Abstract]
- Kim S, Parks CG, DeRoo LA, Chen H, Taylor JA, Cawthon RM, Sandler DP. Obesity and weight gain in adulthood and telomere length. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 18(3):816-820, 2009.[Abstract]
- Hoppin JA, Umbach DM, London SJ, Henneberger PK, Kullman GJ, Coble J, Alavanja MCR, Beane Freeman LE, Sandler DP. Pesticide use and adult-onset asthma among male farmers in the Agricultural Health Study. The European respiratory journal 34(6):1296-1303, 2009.[Abstract]
- Saldana TM, Basso O, Baird DD, Hoppin JA, Weinberg CR, Blair A, Alavanja MCR, Sandler DP. Pesticide Exposure and Hypertensive Disorders During Pregnancy. Environmental health perspectives 117(9):1393-1396, 2009.[Abstract]
- D'Aloisio AA, Baird DD, DeRoo LA, Sandler DP. Association of intrauterine and early-life exposures with diagnosis of uterine leiomyomata by 35 years of age in the Sister Study. Environmental health perspectives 2010; 118(3):375-381.[Abstract]
- Goldner WS, Sandler DP, Yu F, Hoppin JA, Kamel F, LeVan TD. Pesticide use and thyroid disease among women in the Agricultural Health Study. American journal of epidemiology 171(4):455-464, 2010.[Abstract]
- Tanner CM, Kamel F, Ross GW , Hoppin JA , Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade A, Comyns K, Richards M, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW. Rotenone, Paraquat and Parkinson's Disease. Environmental health perspectives 119(6):866-872, 2011.[Abstract]
- Parks CG, Deroo LA, Miller DB, McCanlies EC, Cawthon RM, Sandler DP. Employment and work schedule are related to telomere length in women. Occupational and Environmental Medicine 68(8):582-589, 2011.[Abstract]
- Kim S, Sandler DP, Carswell G, De Roo LA, Parks CG, Cawthon R, Weinberg CR, Taylor JA. Telomere length in peripheral blood and breast cancer risk in a prospective case-cohort analysis: results from the Sister Study. Cancer causes & control 2011 22(7):1061-6.[Abstract]
- Vupputuri S, Parks CG, Nylander-French LA, Owen-Smith A , Hogan SL, Sandler DP. Occupational Silica Exposure and Chronic Kidney Disease. Renal Failure 34(1):40-46, 2012.[Abstract]
- D'Aloisio AA, Baird DD, DeRoo LA, Sandler DP. Early-life exposures and early onset uterine leiomyomata in black women in the Sister Study. Environmental health perspectives 2012 120(3):406-412.[Abstract]
- Fei C , Deroo LA, Sandler DP, Weinberg CR. Fertility drugs and young-onset breast cancer: Results from the Two Sister Study. Journal of the National Cancer Institute 104(13):1021-7, 2012.[Abstract]
- Xu Z, Bolick SCE, DeRoo LA, Weinberg CR, Sandler DP, Taylor JA. Epigenome-wide association study of breast cancer using prospectively collected Sister Study samples. J Natl Cancer Inst (in press) E-pub 2013 Apr 11. PMID: 23578854.
- Kim S, Taylor JA, Milne GL, Sandler DP. Association between Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk: A Prospective, Case-Cohort Study of Postmenopausal Women. Cancer prevention research (Philadelphia, Pa.) 2013 6(6):511-518.[Abstract]
- White AJ, Sandler DP, Bolick SCE, Xu Z, Baldwin K, Taylor JA, DeRoo LA. Recreational and household physical activity at different time points and DNA global methylation. 2013 European journal of cancer. 49:2199-2206.[Abstract]
- Xu Z, Bolick SCE, DeRoo LA, Weinberg CR, Sandler DP, Taylor JA. DNA methylation in blood is associated with breast cancer: A study in prospective samples from the Sister Study. Journal of the National Cancer Institute 105(10):694-700, 2013.[Abstract]
- Beard JD, Hoppin JA, Richards M, Alavanja MC, Blair A, Sandler DP, Kamel F. Pesticide exposure and self-reported incident depression among wives in the Agricultural Health Study. Environmental research 126:31-42, 2013.[Abstract]
- Hoppin JA, Jaramillo R, London SJ, Bertelsen RJ, Salo PM, Sandler DP , Zeldin DC. Phthalate exposure and allergy in the U.S. population: results from NHANES 2005-2006. Environmental health perspectives 2013 121(10):1129-1134.[Abstract]
- Nichols HB, Baird DD, DeRoo DD, Kissling GE, Sandler DP. Tubal ligation in relation to menopausal symptoms and breast cancer risk. British journal of cancer 2013 3(109):1291-1295.[Abstract]
- Kim NH, Mason CC, Nelson RG, Afton SE, Essader AS, Medlin JE, Levine KE, Hoppin JA, Lin C, Knowler WC, Sandler DP. Arsenic exposure and incidence of type 2 diabetes in Southwestern American Indians. American journal of epidemiology 177(9):962-969, 2013.[Abstract]
- Kamel F, Goldman SM, Umbach DM, Chen H, Richardson G, Barber MR, Meng C, Marras C, Korell M, Kasten M, Hoppin JA, Comyns K, Chade A, Blair A, Bhudhikanok GS, Webster Ross G, William Langston J, Sandler DP, Tanner CM. Dietary fat intake, pesticide use, and Parkinson's disease. Parkinsonism & related disorders 20(1):82-87, 2014.[Abstract]
- DeRoo LA, Bolick SCE, Xu Z, Umbach DM, Shore D, Weinberg CR, Sandler DP, Taylor JA. Global DNA methylation and one-carbon metabolism gene polymorphisms and the risk of breast cancer in the Sister Study. Carcinogenesis 35(2):333-338, 2014.[Abstract]
- Weichenthal S, Villeneuve PJ, Burnett RT, van Donkelaar A, Martin RV, Jones RR, DellaValle CT, Sandler DP, Ward MH, Hoppin JA. Long-Term Exposure to Fine Particulate Matter: Association with Nonaccidental and Cardiovascular Mortality in the Agricultural Health Study Cohort. Environmental health perspectives 122(6):609-615, 2014.[Abstract]
- Weinberg CR, Shi M, DeRoo L, Taylor JA, Sandler DP, Umbach DM. Asymmetry in family history implicates nonstandard genetic mechanisms: application to the genetics of breast cancer. PLoS genetics 10(3):e1004174, 2014.[Abstract]
- Hoppin JA, Umbach DM, Long S, Rinsky JL, Henneberger PK, Salo PM, Zeldin DC, London SJ, Alavanja MC, Blair A, Beane Freeman LE, Sandler DP. Respiratory disease in United States farmers. Occupational and environmental medicine 71(7):484-491, 2014.[Abstract]
- Starling AP, Umbach DM, Kamel F, Long S, Sandler DP, Hoppin JA. Pesticide use and incident diabetes among wives of farmers in the Agricultural Health Study. Occupational and environmental medicine 2014 71(9):629-635.[Abstract]
- Goldman SM1, Kamel F, Ross GW, Jewell SA, Marras C, Hoppin JA, Umbach DM, Bhudhikanok GS, Meng C, Korell M, Comyns K, Hauser RA, Jankovic J, Factor SA, Bressman S, Lyons KE, Sandler DP, Langston JW, Tanner CM. Peptidoglycan recognition protein genes and risk of Parkinson's disease. Movement disorders: official journal of the Movement Disorder Society 2014 29(9):1171-1180.[Abstract]
- Beard JD, Umbach DM, Hoppin JA, Richards M, Alavanja MC, Blair A, Sandler DP, Kamel F. Pesticide Exposure and Depression among Male Private Pesticide Applicators in the Agricultural Health Study. Environmental health perspectives 2014 122(9):984-991.[Abstract]
- Quick H, Groth C, Banerjee S, Carlin BP, Stenzel MR, Stewart PA, Sandler DP, Engel LS, Kwok RK. Exploration of the use of Bayesian modeling of gradients for censored spatiotemporal data from the Deepwater Horizon oil spill. Spatial statistics 2014 9():166-179.[Abstract]
- Godfrey AC, Xu Z, Weinberg CR, Getts RC, Wade PA, DeRoo LA, Sandler DP, Taylor JA. Serum microRNA expression as an early marker for breast cancer risk in prospectively collected samples from the Sister Study cohort. Breast cancer research: BCR 2014 15(3):R42-. [Abstract]
- Henneberger PK, Liang X, London SJ, Umbach DM, Sandler DP, Hoppin JA. Exacerbation of symptoms in agricultural pesticide applicators with asthma. International archives of occupational and environmental health 2014 87(4):423-432. [Abstract]
- Nichols HB, DeRoo LA, Scharf DR, Sandler DP. Risk-benefit profiles of women using tamoxifen for chemoprevention. Journal of the National Cancer Institute 2014 107(1):dju354-.[Abstract]
- Parks CG, Miller FW, Satoh M, Chan EK, Andruschenko Z, Birnbaum LS, Jusko TA, Kissling GE, Patel MD, Rose KM, Weinberg C, Zeldin DC, Sandler DP. Reproductive and hormonal risk factors for antinuclear antibodies (ANA) in a representative sample of U.S. women. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2014 23(11):2492-2502. [Abstract]
- Kim S, Rimando J, Sandler DP. Fruit and vegetable intake and urinary levels of prostaglandin e2 metabolite in postmenopausal women. Nutrition and cancer 2015 67(4):580-586.[Abstract]
- Furlong M, Tanner CM, Goldman SM, Bhudhikanok GS, Blair A, Chade A, Comyns K, Hoppin JA, Kasten M, Korell M, Langston JW, Marras C, Meng C, Richards M, Ross GW, Umbach DM, Sandler DP, Kamel F. Protective glove use and hygiene habits modify the associations of specific pesticides with Parkinson's disease. Environment international 2015 75():144-150.[Abstract]
- Eum KD, Seals RM, Taylor KM, Grespin M, Umbach DM, Hu H, Sandler DP, Kamel F, Weisskopf MG. Modification of the association between lead exposure and amyotrophic lateral sclerosis by iron and oxidative stress related gene polymorphisms. Amyotrophic lateral sclerosis & frontotemporal degeneration 2015 16(1-2):72-79.[Abstract]