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Genetics, Environment & Respiratory Disease Group

Genetic Susceptibility & the Environment

Stephanie J. London, M.D., Dr.P.H.
Stephanie J. London, M.D., Dr.P.H.
Principal Investigator



Tel (919) 541-5772
Fax (919) 541-2511
london2@niehs.nih.gov

Curriculum Vitae (http://www.niehs.nih.gov/research/atniehs/labs/epi/genetics/London_cv.pdf)  Download Adobe Reader
P.O. Box 12233
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Research Summary

The Genetics, Environment & Respiratory Disease Group currently focuses on genetic susceptibility and interactions between genetics and the environment in relation to nonmalignant conditions, including asthma and chronic obstructive pulmonary disease. The studies are international in scope, taking advantage of variation in disease rates, environmental exposures and possible protective factors, and allele frequencies to increase the ability to discern etiologic associations. Stephanie J. London, M.D., Dr.P.H, is the head of the Genetics, Environment & Respiratory Disease Group.

London's work on gene-environment interaction in respiratory disease began with studies of lung cancer. In her cohort of Shanghai men, she reported the first example of a gene-diet interaction based on a dietary biomarker. She found that the protective effect of higher intake of isothiocyanates, a chemopreventive substance in Brassica vegetables, was predominantly seen among individuals with genetically impaired ability to eliminate these compounds (GSTM1 null genotype). This finding has been replicated by others. These data suggest association with genetic polymorphisms may vary among populations due to differences in diet and that benefits of chemoprevention may vary among individuals and across populations due to variation in genetic susceptibility.

London now focuses on environmental causes, genetic susceptibility and interactions in relation to nonmalignant respiratory disease, including asthma, chronic respiratory symptoms and chronic obstructive pulmonary disease. London began this work in 1992 when she was part of a small of investigators at the University of Southern California who established the Children's Health Study, a school-based cohort study of health effects of air pollution among Southern California children. After coming to NIEHS in 1995, she established the genetic component of this study, collecting buccal cells from the children to examine candidate gene polymorphisms. This addition to the study was so successful that it subsequently became the basis for extensive extramural funding for the investigators who replaced her at USC.

One international collaboration focuses on the role of diet, genetics and the environment in asthma and chronic bronchitis in adults. This study is conducted within the setting of a cohort study of adults of Chinese ethnicity in Singapore. It was initially funded by the National Cancer Institute to study diet and cancer and features a dietary assessment that is designed for and validated in this population. London added assessment and validation of respiratory outcomes to this study and will use genetic samples to examine gene-diet and gene-environment interactions.

The large proportion of nonsmoking women in this study facilitates the study of other risk factors for respiratory disease. Findings from this study indicate a protective effect of dietary fiber from fruits and soy foods on the development of chronic bronchitis symptoms. In these data, fiber explains associations with antioxidant intake reported in studies that did not adjust for fiber. To better understand the complex interplay between correlated intakes of foods and nutrients, London studied dietary patterns in relation to chronic bronchitis symptoms. This work indicated that independent of fiber intake, high intake of a diet high in fresh and preserved red meat, refined carbohydrates, and sodium was associated with increased risk. This was the first examination of dietary patterns in relation to nonmalignant respiratory disease. The investigators also found that early life exposure to secondhand smoke was related to the development of chronic respiratory symptoms in adulthood among nonsmokers. This effect could be mitigated by adult intake of fiber. In the future, London’s work in the Singapore Cohort will focus on interactions between diet, environment and genetic susceptibility in relation to respiratory endpoints.

London earned a B.A. from Harvard College, an M.D. and an M.P.H in occupational health from Harvard Medical School, and a Dr.P.H. in epidemiology from the Harvard School of Public Health. She is licensed in California, and is Board Certified in Internal Medicine and Preventive Medicine, with Specialty in Occupational and Environmental Medicine. London was Assistant Professor, Department of Preventive Medicine at the University of Southern California School of Medicine, Los Angeles, before coming to NIEHS in 1995. She is currently a Principal Investigator at NIEHS and holds a dual appointment in the Laboratory of Respiratory Biology.

Studies

  • LA Lung Study
    The LA lung study was one of the first studies of genetic susceptibility to lung cancer using population controls and including large numbers of African-Americans. Recently, the study has been included in a number of pooled analyses from the Collaborative Studies on the Genetics of Cancer.
  • Mexico Childhood Asthma Study (http://www.niehs.nih/research/atniehs/labs/epi/studies/mexico/index.cfm)
    The Mexico Childhood Asthma Study is a case-parent triad study of childhood allergic asthma in Mexico City.
  • OBOZ Study (http://www.niehs.nih/research/atniehs/labs/epi/studies/oboz/index.cfm)
    The OBOZ Study will investigate whether obesity affects respiratory response to ozone. It is a collaborative effort between London’s and investigators from the Center for Environmental Medicine and Lung Biology (CEMALB) at the University of North Carolina at Chapel Hill.
  • Shanghai Study
  • Singapore Chinese Health Study (http://www.niehs.nih/research/atniehs/labs/epi/studies/singapore/index.cfm)
    The Singapore Chinese Health Study examines the environmental, dietary and genetic risk factors for respiratory disease. The study will also examine gene-environment and gene-diet interactions with respect to respiratory symptoms and illness.
  • Wuhan Study

Selected Publications

  1. London SJ, Gauderman WJ, Avol E, Rappaport E, Peters JM. Family history and the risk of early onset persistent, early onset transient and late onset asthma. Epidemiology. 2001;12:577-83. [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11505179&query_hl=1&itool=pubmed_docsum)
  2. London SJ, Yuan J-M, Chung FL, Gao YT, Coetzee GA, Yu MC, Ross RK. Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms and lung cancer risk: a prospective study of men in Shanghai, China. Lancet 2000; 356: 724-729. [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11085692&query_hl=4&itool=pubmed_docsum)
  3. London SJ, Yuan J-M, Travlos G, Gao Y-T, Wilson R, Ross RK, Yu MC. Insulin-like growth factor 1, IGF-binding protein 3, and lung cancer risk in a prospective study of men in China. J. Natl Cancer Inst. 2002; 15:749-54. [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12011225&query_hl=4&itool=pubmed_docsum)
  4. David GL, Romieu I, Sienra-Monge JJ, Collins WJ, Ramirez-Aguilar M, del Rio-Navarro BE, Reyes-Ruiz NI, Morris R, Marzec JM, London SJ. Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase and glutathione S-transferase M1 polymorphisms and childhood asthma. Am J Respir Crit Care Med 168:1199-1204, 2003. [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12969868) [Full Text] Exit NIEHS(http://ajrccm.atsjournals.org/cgi/content/full/168/10/1199) [download the PDF] Exit NIEHS(http://ajrccm.atsjournals.org/cgi/reprint/168/10/1199)
  5. Romieu I, Sienra-Monge JJ, Ramirez M, Moreno-Macias H, Reyes-Ruiz NI, del Rio-Navarro BE, Hernandez-Avila M, London SJ. Genetic polymorphism of GSTM1 and antioxidant supplementation influence lung function in relation to ozone exposure among Mexico City children. Thorax 59:8-10, 2004. [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14694237) [Full Text] Exit NIEHS(http://thorax.bmjjournals.com/cgi/content/full/59/1/8) [download the PDF] Exit NIEHS(http://thorax.bmjjournals.com/cgi/reprint/59/1/8)
  6. Butler LM, Koh WP, Lee HP, Yu MC, London SJ. Dietary fiber and reduced cough with phlegm: a cohort study in Singapore. Am J Respir Crit Care Med 170:279-87, 2004. [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15117740) [Full Text] Exit NIEHS(http://ajrccm.atsjournals.org/cgi/content/full/170/3/279) [download the PDF] Exit NIEHS(http://ajrccm.atsjournals.org/cgi/content/full/170/3/279)
  7. David GL, Koh W-P, Lee H-P, Yu MC, London SJ. Childhood exposure to environmental tobacco smoke and chronic respiratory symptoms in nonsmoking adults: Singapore Chinese Health Study. Thorax. 2005;60:1052-8. Epub 2005 Aug 30. [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16131525&query_hl=10&itool=pubmed_docsum)
  8. Butler LM, Koh W-P, Lee H-P, Tseng M, Yu MC, London SJ. Prospective study of dietary patterns and persistent cough with phlegm among Chinese Singaporeans. Am J Respir Crit Care Med. 2006;173:264-70. Epub 2005 Oct 20. [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16239624&query_hl=19&itool=pubmed_docsum)
  9. Li H, Romieu I, Sienra-Monge J-J, Ramirez-Aguilar M, del Rio-Navarro BE, Kistner EO, Gjessing HK, Lara-Sanchez IC, Chiu G, London SJ. Genetic polymorphisms in arginase I and II and childhood asthma and atopy. Journal of Allergy and Clinical Immunology. 2006:117:119-126. [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16387594&query_hl=24&itool=pubmed_docsum)
  10. Levan TD, Koh WP, Lee HP, Koh D, Yu MC, London SJ. Vapor, Dust and Smoke Exposure in Relation to Adult-Onset Asthma and Chronic Respiratory Symptoms: The Singapore Chinese Health Study. American Journal of Epidemiology. 2006;163:1118-28. Epub 2006 May 17. [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16707657&query_hl=27&itool=pubmed_docsum)
  11. Elliott L, Longnecker MP, Kissling GE, London SJ. Volatile organic compounds and pulmonary function in the Third National Health and Nutrition Examination Survey, 1988-1994. Environmental Health Perspectives. 2006;114:1210-4. [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16882527&query_hl=30&itool=pubmed_docsum)
  12. Romieu I, Ramirez-Aguilar M, Sienra-Monge JJ, Moreno-Macias H, Del Rio-Navarro BE, David G, Marzec J, Hernandez-Avila M, London S. GSTM1 and GSTP1 and respiratory health in asthmatic children exposed to ozone. Eur Respir J. 2006 Nov;28(5):953-9. Epub 2006 Jul 26. [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16870661&query_hl=33&itool=pubmed_docsum)
  13. Wu H,Romieu I, Sienra-Monge JJ, del Rio-Navarro BE, Anderson DM, Dunn EW, Steiner LL, Lara-Sanchez I, London SJ. Parental Smoking Modifies the Relation between Genetic Variation in Tumor Necrosis Factor-α (TNF) and Childhood Asthma.  Environmental Health Perspectives, in press.
  14. Li H, Romieu I, Wu H, Sienra-Monge JJ, Ramírez-Aguilar M, del Río-Navarro BE, Lara-Sánchez I, Kistner EO, Gjessing HK, London SJ. Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy. Human Genetics. Epub Feb 28 2007 [Abstract] Exit NIEHS(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17333284&query_hl=37&itool=pubmed_docsum)
  15. Kan H, Heiss G, Rose KM, Whitsel E, Lurmann F, London SJ. Traffic exposure and lung function in adults: the Atherosclerosis Risk in Communities Study. Thorax 62:873-879, 2007. Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17442705)Exit NIEHS
  16. Elliott L, Arbes SJ, Harvey ES, Lee RC, Salo PM, Cohn RD, London SJ, Zeldin DC. Dust weight and asthma prevalence in the National Survey of Lead and Allergens in Housing (NSLAH). Environmental health perspectives 2007 2 (215-220). Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17384767) Exit NIEHS
  17. Bennett WD , Hazucha MJ, Folinsbee LJ, Bromberg PA, Kissling GE, London SJ. Acute pulmonary function response to ozone(O3) in young adults as a function of body mass index (BMI). Inhalation toxicology 2007 19(14):1147-1154. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17987466) Exit NIEHS
  18. Hoppin JA, Valcin M, Henneberger PK, Kullman GJ, Umbach DM, London SJ, Alavanja MCR, Sandler DP. Pesticide use and chronic bronchitis among farmers in the Agricultural Health Study. American journal of industrial medicine 2007 50(12):969-979. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17975796) Exit NIEHS
  19. Kan H, Stevens J, Heiss G, Rose KM, London SJ. Dietary fiber, lung function and chronic obstructive pulmonary disease in the Atherosclerosis Risk in Communities Study. American journal of epidemiology 2007 167(5):570-578. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18063592) Exit NIEHS
  20. Wu H, Romieu I, Sienra-Monge JJ, Rio-Navarro BE, Burdett L, Yuenger J, Chanock SJ, London SJ. Lack of association between genetic variation in G protein-coupled receptor for asthma susceptibility (GPRA) and childhood asthma and atopy. Genes and immunity 2008 9(3):224-230. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18340359) Exit NIEHS
  21. Nystad W , Håberg SE, London SJ, Nafstad P, Magnus P. Baby swimming and respiratory health. Acta paediatrica (Oslo, Norway : 1992) 2008 97(5):657-662. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18394113) Exit NIEHS
  22. Elliott L, Henderson J, Northstone K, Chiu GY, Dunson D, London SJ. Prospective study of breastfeeding in relation to wheeze, atopy, and bronchial hyperresponsiveness in the Avon Longitudinal Study of Parents and Children (ALSPAC). Lancet 2008 122(1):49-54. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18468669) Exit NIEHS

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Last Reviewed: June 13, 2008