Biography

Dr. Lan received her PhD in molecular epidemiology at the Chinese Academy of Preventive Medicine in Beijing, as part of a joint training program with the United States Environmental Protection Agency and University of North Carolina at Chapel Hill, and received her MPH at Johns Hopkins University. Her research focuses on molecular epidemiologic studies of populations exposed to several classes of chemical compounds that are known or suspected occupational and environmental carcinogens.

Research Interests

We are conducting molecular epidemiologic studies of populations exposed to well-defined classes of chemical compounds that are known or suspected carcinogens, including polycyclic aromatic hydrocarbons (PAHs), benzene, formaldehyde, and trichloroethylene. We use biologic markers to assist in exposure assessment, provide new insights into mechanism of action, and evaluate genetic susceptibility and gene-environment interactions.

Molecular Epidemiology Studies of Indoor Air Pollution and Lung Cancer

According to the World Health Organization, exposure to smoke from open fires in homes is the fourth biggest health risk in developing countries with 1.4 billion people being at risk, and an estimated 40 million disability adjusted life years are lost every year. Studies have linked coal smoke and PAH exposure and an excess of lung cancer in China. Previous studies suggest that 1) lung cancer and chronic obstructive pulmonary disease rates declined due to improved home ventilation; 2) genetic susceptibility may make an important contribution to the risk of lung cancer particularly in women; and 3) lung tumors from individuals with high levels of smoky coal exposure have distinctive molecular characteristics. Ongoing research includes investigating the pathogenesis of PAH-driven lung cancer among nonsmoking women by studying the overall impact of genetic variation in genes that activate and detoxify PAHs, repair DNA damaged by bulky adducts and oxidation, and maintain cell cycle control on cancer risk, and potential gene-environment interactions.

Molecular Epidemiology Studies of Benzene, Trichloroethylene, and Formaldehyde

Benzene is known to have toxic effects on the blood and bone marrow and is a known leukemogen and suspect lymphomagen, but its impact at levels below the U.S. occupational standard of 1 part per million (ppm) remains uncertain. We carried out a study with detailed exposure assessment to investigate the effect of benzene exposure below 1 ppm and found that white blood cell and platelet counts were significantly lower than controls for exposure below 1 ppm in air. We are evaluating additional hematologic changes, cytogenetic abnormalities, and altered proteomic and mRNA expression in workers exposed to benzene. Interindividual variation to benzene-induced hematotoxicity has been observed in occupational studies, in which highly disparate responses have been noted among workers with similar benzene exposure, suggesting a role for individual genetic susceptibility. We are using high throughput genotyping of single nucleotide polymorphisms (SNPs) with an Oligo Pool (OPA) by Illumina®, which can analyze a large number of SNPs potentially related to benzene hematotoxicity. In addition, we are carrying out molecular studies to identify, validate, and quantify candidate biomarkers, such as peripheral blood nuclear DNA telomere length and mitochondrial DNA (mtDNA) mass, that may provide additional insight into the underlying mechanism of benzene-induced damage to the genome.

Trichloroethylene (TCE) is a ubiquitous environmental contaminant of drinking water and is present in many EPA Superfund sites. TCE is a rodent carcinogen, and has been associated with increased risk of non-Hodgkin lymphoma (NHL) and kidney cancer in some but not all epidemiologic studies. We recently conducted a cross-sectional study of early biologic effect biomarkers of genotoxicity and immunotoxicity in workers exposed to TCE and unexposed controls in Guangdong Province, China. Our goal is to determine if TCE exposure increases chromosomal aberrations in peripheral lymphocytes, and if TCE alters levels of key cytokines in plasma and changes lymphocyte subset ratios.

Epidemiologic studies suggest that occupational exposure to formaldehyde may be associated with increased risk for myeloid leukemia. The significance, however, of these observations for occupational and environmental health is uncertain because of inconsistencies among epidemiologic studies and lack of a demonstrated mechanism through which formaldehyde can cause leukemia. Cytogenetic damage is one potential leukemogenic mechanism, but there are few studies of formaldehyde-exposed humans. Some experimental data suggest that epigenetic changes in myeloid cells could also be involved. We carried out a study of workers exposed to formaldehyde and unexposed controls to determine if formaldehyde exposure is related to increased levels of myeloid leukemia-related chromosomal abnormalities in circulating early myeloid progenitor cells cultured from peripheral blood.

Genetic Susceptibility of Non-Hodgkin Lymphoma

We are currently evaluating the role of genetic polymorphisms in a population-based case-control study of NHL among women in Connecticut. We conducted a large-scale evaluation of SNPs in selected candidate genes for cancer to identify genes that influence NHL risk. Ongoing studies include investigating SNPs in candidate genes that are relevant for immune, DNA repair, one-carbon metabolism, cell cycle control, and oxidative stress related pathways that are hypothesized to play a role in NHL etiology. In addition, we have found that a number of genetic variants that increase susceptibility for benzene-mediated lymphocyte toxicity are also associated with risk of NHL, suggesting that these genes may make a fundamental contribution to maintaining hematologic homeostasis. Further, we are evaluating biomarkers of environmental exposure and early biologic effect, including several we are studying among workers exposed to benzene and TCE, in nested case-control studies of NHL in several prospective cohorts.

Keywords

Occupational exposure, polycyclic aromatic hydrocarbons, benzene, formaldehyde, trichloroethylene, molecular epidemiology, genetic susceptibility, gene-environment interaction, lung cancer, and non-Hodgkin lymphoma

Selected Publications

• Lan Q, He X, Costa DJ, Tian L, Rothman N, Hu G, Mumford JL. "Indoor coal combustion emissions, GSTM1 and GSTT1 genotypes, and lung cancer risk: a case-control study in Xuan Wei, China." Cancer Epidemiol Biomarkers Prev. 2000;9(6):605-8.
• Lan Q, Chapman RS, Schreinemachers DM, Tian L, He X. "Household stove improvements and reduction of lung cancer risk in Xuan Wei, China." J Natl Cancer Inst. 2002;94(11):826-35.
• Vermeulen R, Li G, Lan Q, Dosemeci M, Rappaport SM, Xu B, Smith MT, Zhang L, Hayes RB, Linet M, Mu R, Wang L, Xu J, Yin S, Rothman N. "Detailed exposure assessment for a molecular epidemiology study of benzene in two shoe factories in China." Ann Occup Hyg. 2004;48(2):105-16. 
• Lan Q, Mumford JL, Shen M, Demarini DM, Bonner MR, He X, Yeager M, Welch R, Chanock S, Tian L, Chapman RS, Zheng T, Keohavong P, Caporaso N, Rothman N. "Oxidative damage-related genes AKR1C3 and OGG1 modulate risks for lung cancer due to exposure to PAH-rich coal combustion emissions." Carcinogenesis. 2004;25(11):2177-81.
• Lan Q, Zhang L, Li G, Vermeulen R, Weinberg RS, Dosemeci M, Rappaport SM, Shen M, Alter BP, Wu Y, Kopp W, Waidyanatha S, Rabkin C, Guo W, Chanock S, Hayes RB, Linet M, Kim S, Yin S, Rothman N, Smith MT. "Hematotoxicity in workers exposed to low levels of benzene." Science. 2004;306(5702):1774-6.
• Bonner MR, Rothman N, Mumford JL, He X, Shen M, Welch R, Yeager M, Chanock S, Caporaso N, Lan Q. "Green tea consumption, genetic susceptibility, PAH-rich smoky coal, and the risk of lung cancer." Mutat Res. 2005;582(1-2):53-60.
• Forrest MS, Lan Q, Hubbard AE, Zhang L, Vermeulen R, Zhao X, Li G, Wu YY, Shen M, Yin S, Chanock SJ, Rothman N, Smith MT. "Discovery of novel biomarkers by microarray analysis of peripheral blood mononuclear cell gene expression in benzene-exposed workers." Environ Health Perspect. 2005;113(6):801-7.
• Shen M, Berndt SI, Rothman N, Demarini DM, Mumford JL, He X, Bonner MR, Tian L, Yeager M, Welch R, Chanock S, Zheng T, Caporaso N, Lan Q. "Polymorphisms in the DNA nucleotide excision repair genes and lung cancer risk in Xuan Wei, China." Int J Cancer. 2005;116(5):768-73.
• Lan Q, Zhang L, Shen M, Smith MT, Li G, Vermeulen R, Rappaport SM, Forrest MS, Hayes RB, Linet M, Dosemeci M, Alter BP, Weinberg RS, Yin S, Yeager M, Welch R, Waidyanatha S, Kim S, Chanock S, Rothman N. "Polymorphisms in Cytokine and Cellular Adhesion Molecule Genes and Susceptibility to Hematotoxicity among Workers Exposed to Benzene. Cancer Res. 2005;65(20):9574-81.
• Chapman RS, He X, Blair AE, Lan Q. "Improvement in household stoves and risk of chronic obstructive pulmonary disease in Xuanwei, China: retrospective cohort study." BMJ. 2005;331(7524):1050.
• Zhang Y, Lan Q, Rothman N, Zhu Y, Zahm SH, Wang S, Holford TR, Leaderer B, Boyle P, Zhang B, Zou K, Chanock S, Zheng T. "An exonic splicing polymorphism in the BCL6 gene and risk of non-Hodgkin lymphoma." J Natl Cancer Inst. 2005;97(21):1616-8.
• Vermeulen R, Lan Q, Zhang L, Gunn L, McCarthy D, Dalmasso EA, McGuire M, Podust V, Li G, Chatterjee N, Rothman N, Smith MT. "Decreased levels of CXC-chemokines in serum of benzene-exposed workers identified by SELDI-TOF MS based proteomics." Proc Natl Acad Sci U S A. 2005;102(47):17041-6.
• Rothman N, Skibola CF, Wang SS, Morgan G, Lan Q, Smith MT, Spinelli JJ, Willett E, De Sanjose S, Cocco P, Berndt SI, Brennan P, Brooks-Wilson A, Wacholder S, Becker N, Hartge P, Zheng T, Roman E, Holly EA, Boffetta P, Armstrong B, Cozen W, Linet M, Bosch FX, Ennas MG, Holford TR, Gallagher RP, Rollinson S, Bracci PM, Cerhan JR, Whitby D, Moore PS, Leaderer B, Lai A, Spink C, Davis S, Bosch R, Scarpa A, Zhang Y, Severson RK, Yeager M, Chanock S, Nieters A. "Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium." Lancet Oncol. 2006;7(1):27-38.
• Lan Q, Zheng T, Rothman N, Zhang Y, Wang S, Shen M, Zhu Y, Zahm SH, Holford TR, Leaderer B, Boyle P, Zhang B, Chanock S. "Cytokine polymorphisms in the Th1/Th2 pathway and risk of NHL in a population-based case-control study of women in Connecticut." Blood. 2006;107(10):4101-8.
• Shen M, Zheng T, Lan Q, Zhang Y, Zahm SH, Wang S, Holford TR, Leaderer B, Yeager M, Welch R, Kang D, Boyle P, Zhang B, Zou K, Zhu Y, Chanock S, Rothman N. "Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut." Hum Genet. 2006;119(6):659-68.

Collaborators

DCEG Collaborators

• Michael Alavanja, Ph.D., Demetrius Albanes, M.D., Ph.D., Dalsu Baris, M.D., Ph.D., Aaron Blair, Ph.D., Neil Caporaso, M.D., Stephen Chanock, M.D., Richard Hayes, Ph.D., Butian Ji, Ph.D., Martha Linet, M.D., Jay Lubin, Ph.D., Mark Purdue, Ph.D., Meredith Yeager, Ph.D., Nat Rothman, M.D., Min Shen, Ph.D., Sophia Wang, Ph.D., Sholom Wacholder, Ph.D. Robert Welch, Ph.D., Kai Yu, Ph.D., Shelia Zahm, Sc.D.

Other NCI Collaborators

• Graca Dores, M.D., Patricia Hartge, Sc.D., Mimi Poirier, Ph.D.

Other Scientific Collaborators

• Wing Yan Au, M.D., Queen Mary Hospital, Hong Kong
• Robert Chapman, M.D., United States Environmental Protection Agency, Research Triangle Park, NC
• Daehee Kang, Ph.D., Judy Mumford, Ph.D., United States Environmental Protection Agency, Research Triangle Park, NC
• Stephen Rapport, Ph.D., University of North Carolina, Chapel Hill, NC
• Martyn Smith, Ph.D., University of California at Berkeley, Berkeley, CA
• Roel Vermeulen, Ph.D., Utrecht University, the Netherlands
• Tongzhang Zheng, Sc.D., Yale University, New Haven, CT