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

• Hosgood HD 3rd, Wei H, Sapkota A, Choudhury I, Bruce N, Smith KR, Rothman N, Lan Q. Household coal use and lung cancer: systematic review and meta-analysis of case-control studies, with an emphasis on geographic variation. Int J Epidemiol. 2011;40(3):719-28.
• Lan Q, Wang SS, Menashe I, Armstrong B, Zhang Y, Hartge P, Purdue MP, Holford TR, Morton LM, Kricker A, Cerhan JR, Grulich A, Cozen W, Zahm SH, Yeager M, Vajdic CM, Schenk M, Leaderer B, Yuenger J, Severson RK, Chatterjee N, Chanock SJ, Zheng T, Rothman N. Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin lymphoma: a pooled analysis of three population-based case-control studies. Br J Haematol. 2011;153(3):341-50.
• Hsiung CA, Lan Q, Hong YC, Chen CJ, Hosgood HD, Chang IS, Chatterjee N, Brennan P, Wu C, Zheng W, Chang GC, Wu T, Park JY, Hsiao CF, Kim YH, Shen H, Seow A, Yeager M, Tsai YH, Kim YT, Chow WH, Guo H, Wang WC, Sung SW, Hu Z, Chen ZY, Kim JH, Chen Y, Huang L, Lee KM, Lo YL, Gao YT, Kim JH, Liu L, Huang MS, Jung TH, Jin G, Caporaso N, Yu D, Kim CH, Su WC, Shu XO, Xu P, Kim IS, Chen YM, Ma H, Shen M, Cha SI, Tan W, Chang CH, Sung JS, Zhang M, Yang TY, Park KH, Yuenger J, Wang CL, Ryu JS, Xiang Y, Deng Q, Hutchinson A, Kim JS, Cai Q, Landi MT, Yu CJ, Park JY, Tucker M, Hung JY, Lin CC, Perng RP, Boffetta P, Chen CY, Chen KC, Yang SY, Hu CY, Chang CK, Fraumeni JF, Chanock S, Yang PC, Rothman N, Lin D. The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia. PLoS Genet. 2010;5;6(8).
• Zhang L, Tang X, Rothman N, Vermeulen R, Ji Z, Shen M, Qiu C, Guo W, Liu S, Reiss B, Freeman LB, Ge Y, Hubbard AE, Hua M, Blair A, Galvan N, Ruan X, Alter BP, Xin KX, Li S, Moore LE, Kim S, Xie Y, Hayes RB, Azuma M, Hauptmann M, Xiong J, Stewart P, Li L, Rappaport SM, Huang H, Fraumeni JF Jr, Smith MT, Lan Q. Occupational exposure to formaldehyde, hematotoxicity, and leukemia-specific chromosome changes in cultured myeloid progenitor cells. Cancer Epidemiol Biomarkers Prev. 2010;19(1):80-8.
• Hosgood HD 3rd, Liu CS, Rothman N, Weinstein SJ, Bonner MR, Shen M, Lim U, Virtamo J, Cheng WL, Albanes D, Lan Q. Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study. Carcinogenesis. 2010 May;31(5):847-9.
• Lan Q, Cawthon R, Shen M, Weinstein SJ, Virtamo J, Lim U, Hosgood HD 3rd, Albanes D, Rothman N. A prospective study of telomere length measured by monochrome multiplex quantitative PCR and risk of non-Hodgkin lymphoma. Clin Cancer Res. 2009 Dec 1;15(23):7429-33.
• Shen M, Chapman RS, Vermeulen R, Tian L, Zheng T, Chen BE, Engels EA, He X, Blair A, Lan Q. Coal use, stove improvement, and adult pneumonia mortality in Xuanwei, China: a retrospective cohort study. Environ Health Perspect. 2009;117(2):261-6.
• Lan Q, Lim U, Liu CS, Weinstein SJ, Chanock S, Bonner MR, Virtamo J, Albanes D, Rothman N. A prospective study of mitochondrial DNA copy number and risk of non-Hodgkin lymphoma. Blood. 2008;112(10):4247-9.
• Lim U, Wang SS, Hartge P, Cozen W, Kelemen LE, Chanock S, Davis S, Blair A, Schenk M, Rothman N, Lan Q. Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER case-control study. Blood. 2007;109(7):3050-9.
• 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.
• Lan Q, Chapman RS, Schreinemachers DM, Tian L, He X. Household stove improvement and risk of lung cancer in Xuanwei, China. J Natl Cancer Inst. 2002;94(11):826-35.

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., Bu-Tian 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., Patricia Hartge, Sc.D.

Other NCI Collaborators

• Graca Dores, M.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
• Richard Hayes, D.D.S., Ph.D., NYU Langone Medical Center, NY, NY
• 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