Project 1: Biomarkers of Benzene Exposure and Leukemia Risk

Summary

Benzene is an important industrial chemical, a component of gasoline, and a prominent contaminant at Superfund sites. Although benzene is an undisputed cause of human leukemia, many important scientific and regulatory questions remain regarding the exposure-response relationship and mechanism of action. In particular, we plan to confirm our earlier finding that humans possess a second metabolic pathway that efficiently metabolizes benzene at low doses and determine whether enzymatic activity varies with gender and smoking status. We suspect that the enzymes CYP2F1 and CYP2A13 are responsible for the low dose metabolism of benzene. We will test this hypothesis and determine the effect of genetic variation in these enzymes on benzene metabolism and health effects among subjects with different levels of benzene exposure.  The effect of variation in other candidate genes will also be explored using high-throughput genotyping, fine mapping and resequencing allowing us the better predict risks of leukemia require at low levels of benzene exposure in genetically susceptible populations. We will also develop biomarkers of early effect and historical exposure. We previously used microarrays to show that the blood mRNA transcriptome is exquisitely sensitive to low level occupational benzene exposure. Here we propose to develop a simple biomarker of ~10 genes, altered in expression by benzene, which may serve as a biomarker of early effect for low level benzene exposure that could readily be used in a field setting such as a Superfund site. We will also measure changes in global and gene-specific DNA methylation and microRNA expression induced by benzene exposure in the blood cells of exposed workers. The goal is to determine if benzene can produce epigenetic changes of the type observed in leukemia, in addition to inducing chromosomal damage, thereby providing important mechanistic insight. Further, we will compare the effects of benzene on gene-specific DNA methylation and microRNA expression with previously determined changes in gene expression. Finally, we will compare the DNA methylation profiles of blood cells from workers with current exposure to benzene with those with a past history of benzene exposure but with no current exposure and with control workers never exposed occupationally to benzene. This will allow us to search for epigenetic marks that might serve as a biomarker of historical exposure to benzene. The overall goal is to use biomarkers to improve the risk assessment of benzene at Superfund sites.

This work is relevant because benzene, an economically important chemical to which we are all exposed is commonly found at Superfund sites and is an established cause of leukemia.  We plan to gain further understanding of the mechanism of benzene-induced leukemia, the risks it poses at low levels and develop tests which can measure past exposure and sensitive effects on the blood. Results obtained from these studies should be of great use to public health regulatory agencies evaluating the risk posed by exposure to benzene.

Project Leadership

Martyn T. Smith, PhD

Professor of Toxicology

Environmental Health Sciences,
School of Public Health
University of California, Berkeley

Stephen M. Rappaport, PhD

Professor

Environmental Health Sciences,
School of Public Health
University of California, Berkeley

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News Archive

Selected Publications

2016

Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell JC, Kavlock RJ, Lambert P, Hecht SS, Bucher JR, Stewart BW, Baan R, Cogliano VJ, Straif K (2016) Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis. Environ Health Perspect. Jun;124(6): 713-721. PMCID: PMC4892922. [PDF]

Carlos-Wallace FM, Zhang L, Smith MT, Rader G, Steinmaus C (2016) Parental, In Utero, and Early-Life Exposure to Benzene and the Risk of Childhood Leukemia: A Meta-Analysis. Am J Epidemiol. Jan 1;183(1):1-14. PMCID: PMC4751231. [PDF]

Fejerman L, Sanchez SS, Thomas R, Tachachartvanich P, Riby J, Gomez SL, John EM, Smith MT (2016) Association of lifestyle and demographic factors with estrogenic and glucocorticogenic activity in Mexican American women. Carcinogenesis. Sep;37(9):904-11. PMCID: PMC5008251. [PDF]

Dennis KK, Auerbach SS, Balshaw DM, Cui Y, Fallin MD, Smith MT, Spira A, Sumner S, Miller GW (2016) The Importance of the Biological Impact of Exposure to the Concept of the Exposome. Environ Health Perspect. Jun 3. [Epub ahead of print]. DOI: 10.1289/EHP140. PMID: 27258438. (PMC Journal – In Process). [PDF]

Bassig BA, Zhang L, Vermeulen R, Tang X, Li G, Hu W, Guo W, Purdue MP, Yin S, Rappaport SM, Shen M, Ji Z, Qiu C, Ge Y, Hosgood HD, Reiss B, Wu B, Xie Y, Li L, Yue F, Freeman LE, Blair A, Hayes RB, Huang H, Smith MT, Rothman N, Lan Q (2016) Comparison of hematological alterations and markers of B-cell activation in workers exposed to benzene, formaldehyde and trichloroethylene. Carcinogenesis. Jul;37(7):692-700. PMCID: PMC4936387. [PDF]

2015

Smith MT, de la Rosa R, Daniels SI (2015) Using exposomics to assess cumulative risks and promote health. Environ Mol Mutagen. Dec;56(9):715-23. PMCID: PMC4636923.

Landrigan PJ, Wright RO, Cordero JF, Eaton DL, Goldstein BD, Hennig B, Maier RM, Ozonoff DM, Smith MT, Tukey RH (2015) The NIEHS Superfund Research Program: Twenty-Five Years of Translational Research for Public Health. Environ Health Perspect. Oct;123(10)909-18. PMCID: PMC4590764. [PDF]

Loomis D, Guyton K, Grosse Y, El Ghissasi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Mattock H, Straif K; International Agency for Research on Cancer Monograph Working Group, IARC, Lyon, France (2015) Carcinogenicity of lindane, DDT, and 2,4-dichlorophenoxyacetic acid. Lancet Oncol. Aug;16(8):891-2. doi: 10.1016/S1470-2045(15)00081-9. PMID: 26111929. [PDF]

Pearce NE, Blair A, Vineis P, Ahrens W, Andersen A, Anto JM, Armstrong BK, Baccarelli AA, Beland FA, …, Smith MT, et al. (2015) IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans. Environ Health Perspect. Jun;123(6):507-14. PMCID: PMC4455595. [PDF]

Sampson JN, Wheeler WA, Yeager M, Panagiotou O, Wang Z, Berndt SI, Lan Q, …,Smith MT, et al. (2015) Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types. J Natl Cancer Inst. Oct 12;107(12). PMCID: PMC4806328. [PDF]

2014

North M, Shuga J, Fromowitz M, Loguinov A, Shannon K, Zhang L, Smith MT and Vulpe CD (2014) Modulation of Ras signaling alters the toxicity of hydroquinone, a benzene metabolite and component of cigarette smoke. BMC Cancer. Jan 5;14(1):6. PMCID: PMC3898384. [PDF]

Thomas R, Hubbard AE, McHale CM, Zhang L, Rappaport SM, Lan Q, et al. (2014) Characterization of changes in gene expression and biochemical pathways at low levels of benzene exposure. PLoS One. 9(5):e91828. PMCID: PMC4006721. [PDF]

Wild CP, Bucher JR, de Jong BW, Dillner J, von Gertten C, Groopman JD, Herceg Z, Holmes E, Holmila R, Olsen JH, Ringborg U, Scalbert A, Shibata T, Smith MT, Ulrich C, Vineis P, McLaughlin J (2014) Translational cancer research: balancing prevention and treatment to combat cancer globally. J Natl Cancer Inst. Dec 16;107(1):353. PMCID: PMC4334834. [PDF]

McHale CM, Smith MT, Zhang L (2014) Application of toxicogenomic profiling to evaluate effects of benzene and formaldehyde: from yeast to human. Ann N Y Acad Sci. 1310:74-83. PMCID: PMC3978411. [PDF]

Rappaport SM, Barupal DK, Wishart D, Vineis P, Scalbert A (2014) The blood exposome and its role in discovering causes of disease. Environ Health Perspect. Aug 122(8):769-74. PMCID: PMC4123034. [PDF]

Bassig BA, Zhang L, Cawthon RM, Smith MT, Yin S, Li G, et al. (2014) Alterations in leukocyte telomere length in workers occupationally exposed to benzene. Environ Mol Mutagen. 55(8):673-8. PMCID: PMC4360990. [PDF]

McHale CM, Zhang L, Lan Q, Vermeulen R, Li G, Hubbard AE, et al. (2011) Global gene expression profiling of a population exposed to a range of benzene levels. Environ Health Perspect. 119(5):628-34. PMCID: PMC3074412. [PDF]

2013

Rappaport SM, Kim S, Thomas R, Johnson BA, Bois FY, Kupper LL (2013) Low-dose metabolism of benzene in humans: science and obfuscation. Carcinogenesis. 34(1): 2-9. PMCID: PMC3584950.

Rappaport SM, Johnson BA, Bois FY, Kupper LL, Kim S, Thomas R (2013) Ignoring and adding errors do not improve the science. Carcinogenesis. Jul;34(7):1689-91. PMCID: PMC3697890. [PDF]

Herceg Z, Lambert MP, van Veldhoven K, Demetriou C, Vineis P, Smith MT, Straif K, Wild CP (2013) Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation. Carcinogenesis. Sep;34(9):1955-67. PMCID: PMC3765050. [PDF]

Metayer C, Zhang L, Wiemels JL, Bartley K, Schiffman J, Ma X, Aldrich MC, Chang JS, Selvin S, Fu CH, Ducore J, Smith MT, Buffler PA (2013) Tobacco Smoke Exposure and the Risk of Childhood Acute Lymphoblastic and Myeloid Leukemias by Cytogenetic Subtype. Cancer Epidemiol Biomarkers Prev. Sep;22(9):1600-11. PMCID: PMC3769478.

Shuga J, Zeng Y, Novak R, Lan Q, Tang X, Rothman N, Vermeulen R, Li L, Hubbard A, Zhang L, Mathies R, Smith MT (2013) Single molecule quantitation and sequencing of rare translocations using microfluidic nested digital PCR. Nucleic Acids Res. Sep 1:41(16):e159. PMCID: PMC3763562.

Hebels DG, Georgiadis P, Keun HC, Athersuch TJ, Vineis P, Vermeulen R, Portengen L, Bergdahl IA, Hallmans G, Palli D, Bendinelli B, Krogh V, Tumino R, Sacerdote C, Panico S, Kleinjans JC, de Kok TM, Smith MT, Kyrtopoulos SA (2013) Performance in Omics Analyses of Blood Samples in Long-Term Storage: Opportunities for the Exploitation of Existing Biobanks in Environmental Health Research. Environ Health Perspect. Apr;121(4):480-7. PMCID: PMC3620742.

Howcroft TK, Campisi J, Louis GB, Smith MT, Wise B, Wyss-Coray T, Augustine AD, McElhaney JE, Kohanski R, Sierra F (2013) The role of inflammation in age-related disease. Aging (Albany NY). Jan;5(1):84-93. PMCID: PMC3616233.

Rappaport SM, Kim S, Thomas R, Johnson BA, Bois FY, Kupper LL (2013) Low-dose metabolism of benzene in humans: science and obfuscation. Carcinogenesis. Jan;34(1):2-9. PMID: 23222815. (PMC Journal – In Process). [PDF]

Ren X, Ji Z, Yuh J, Tang M, Bersonda J, Smith MT, Zhang L (2013) The impact of FANCD2 deficiency on formaldehyde-induced toxicity in human lymphoblastoid cell lines. Arch Tox, jan;87(1):189-196. PMCID: PMC4312773. [PDF]

Zhang L, Bassig BA, Mora JL, Vermeulen R, Ge Y, Curry JD, Hu W, Shen M, Qiu C, Ji Z, Reiss B, McHale CM, Liu S, Guo W, Purdue MP, Yue F, Li L, Smith MT, Huang H, Tang X, Rothman N, Lan Q (2013) Alterations in serum immunoglobulin levels in workers occupationally exposed to trichloroethylene. Carcinogenesis. Jan16. [Epub ahead of print]. PMID: 23276795. (PMC Journal- In Progress). [PDF]

2012

Zhang L, Lan Q, Ji Z, Li G, Shen M, Vermeulen R, Guo W, Hubbard A, McHale CM, Rappaport SM, Hayes RB, Linet B, Yin S, Fraumeni JF, Rothman N, Smith MT (2012). Leukemia-related chromosomal loss detected in hematopoietic progenitor cells of benzene-exposed workers.Leukemia. Dec;26(12):2494-2498. PMCID: PMC3472034. [PDF]

O’Connor ST, Lan J, North M, Loguinov A, Zhang L, Smith MT, Gu A, Vulpe C (2012) Genome-wide functional and stress response profiling reveals toxic mechanism and genes required for tolerance to benzo[a]pyrene in S. cerevisiae. Front in Toxicogenomics. Dec;doi: 10.3389/fgene.2012.00316. (PMC Journal – In Process). [PDF]

Vermeulen R, Zhang L, Spirenburg A, Tang X, Bonventre JV, Reiss B, Shen M, Smith MT, Qui C, Ge Y, Ji Z, Xiong J, He J, Hao Z, Liu S, Xie Y, Yue F, Guo W, Purdue M, Beane-Freeman LE, Sabbisetti V, Li L, Huang H, Rothman N, Lan Q (2012) Kidney toxicity in Chinese factory workers exposed to trichloroethylene. Carcinogenesis. Aug;33(8):1538-41. PMID: 22730190. [PDF]

Ji Z, Weldon RH, Marchetti F, Chen H, Li G, Xing C, Kurtovich E, Young S, Schmid TE, Waidyanatha S, Rappaport SM, Zhang L, Eskenazi B (2012) Comparison of aneuploidies of chromosomes 21, X, and Y in the blood lymphocytes and sperm cells among workers exposed to benzene. Environ Mol Mutagen. Apr;53(3):218-26. PMID: 22351378. (PMC Journal – In Process). [PDF]

Marchetti F, Eskenazi B, Weldon RH, Li G, Zhang L, Rappaport SM, Schmid TE, Xing C, Kurtovich E, Wyrobek AJ (2012) Occupational exposure to benzene and chromosomal structural aberrations in the sperm of Chinese men. Environ Health Perspect. Feb;120(2):229-34. PMCID: PMC3279447. [PDF]

Godderis L, Thomas R, Hubbard AE, Tabish AM, Hoet P, Zhang L, Smith MT, Veulemans H,  McHale CM (2012) Effect of Chemical Mutagens and Carcinogens on Gene Expression Profiles in Human TK6 Cells. PLoS One. 7(6):e39205. PMCID: PMC3377624. [PDF]

2011

Hosgood HD, Zhang L, Tang X, Vermeulen R, Shen M, Smith MT, Blair A, Qui C, Ge Y, Ji Z, Xiong J, He J, Reiss B, Liu S, Xie Y, Guo W, Galvan N, Li L, Hao Z, Rothman N, Huang H, Lan Q (2011) Decreased numbers of CD4+ naive and effector memory T cells, and CD8+ naïve T cells, are associated with trichloroethylene exposure. Front Oncol. 1:53. PMCID: PMC3355872. [PDF]

Chang JS, Zhou M, Buffler PA, Chokkalingam AP, Metayer C, Wiemels JL (2011) Profound Deficit of IL10 at Birth in Children Who Develop Childhood Acute Lymphoblastic Leukemia.Cancer Epidemiol Biomarkers Prev. Aug;20(8):1736-40. PMID: 21653647. [PDF]

Smith MT, Zhang L, McHale CM, Skibola CF, Rappaport SM (2011) Benzene, the exposome and future investigations of leukemia etiology. Chem Biol Interact. Jun 30;192(1-2):155-9. PMID: 21333640. [PDF]

Shen M, Zhang L, Lee KM, Vermeulen R, Hosgood HD, Li G, Yin S, Rothman N, Chanock S, Smith MT, Lan Q (2011) Polymorphisms in genes involved in innate immunity and susceptibility to benzene-induced hematotoxicity. Exp mol Med. Jun 30;43(6):374-8. PMCID: PMC3128916. [PDF]

Ren X, Aleshin M, Jo WJ, Dills R, Kalman DA, Vulpe CD, Smith MT, Zhang L (2011) Involvement of N-6 Adenine-Specific DNA Methyltransferase 1 (N6AMT1) in Arsenic Biomethylation and Its Role in Arsenic-Induced Toxicity. Environ Health Perspect. Jun;119(6):771-7. PMCID: PMC3114810. [PDF]

McHale CM, Zhang L, Lan Q, Vermeulen R, Li G, Hubbard AE, Porter KE, Thomas R, Portier CJ, Shen M, Rappaport SM, Yin S, Smith MT, Rothman N (2011) Global Gene Expression Profiling of a Population Exposed to a Range of Benzene Levels. Environ Health Perspect. May;119(5):628-34. PMCID: PMC3094412. [PDF]

Zhang L, Lan Q, Guo W, Hubbard AE, Li G, Rappaport SM, McHale CM, Shen M, Ji Z, Vermeulen R, Yin S, Rothman N, Smith MT (2011) Chromosome-Wide Aneuploidy Study (CWAS) in Workers Exposed to an Established Leukemogen, Benzene. Carcinogenesis. Apr;32(4):605-12. PMCID: PMC3066415. [PDF]

Urayama KY, Ma X, Selvin S, Metayer C, Chokkalingam AP, Wiemels JL, Does M, Chang J, Wong A, Trachthenberg E, Buffler PA (2011) Early Life exposure to infections and risk of childhood acute lymphoblastic leukemia. Int J Cancer. Apr 1;128(7):1632-43. PMID: 21280034.  [PDF]

Does M, Scélo G, Metayer C, Selvin S, Kavet R, Buffler PA (2011) Exposure to electrical contact currents and the risk of childhood leukemia. Radiat Res. Mar;175(3):390-6. PMID: 21388283. [PDF]

Metayer C, Scélo G, Chokkalingam AP, Barcellos LF, Aldrich MC, Chang JS, Guha N, Urayama KY, Hansen HM, Block G, Kiley V, Wiencke JK, Wiemels JL, Buffler PA (2011) Genetic variants in the folate pathway and risk of childhood acute lymphoblastic leukemia. Cancer Causes Control. Sep;22(9):1243-58. PMID: 21748308. [PDF]

Ren X, Lim S, Ji Z, Yuh J, Peng V, Smith MT, Zhang L (2011) Comparison of Proliferation and Genomic Instability Responses to WRN Silencing in Hematopoietic HL60 and TK6 Cells. PLoS One. Jan 18;6(1):e14546. PMCID: PMC3022623. [PDF]

Novak R, Zeng Y, Shuga J, Venugopalan G, Fletcher DA, Smith MT, Mathies RA (2011) Single cell multiplex gene detection and sequencing with microfluidically generated agarose emulsions. Angew Chem Int Ed Engl. Jan 10;50(2):390-5. PMCID: PMC3027204. [PDF]

2010

Bartley K, Metayer C, Selvin S, Ducore J, Buffler PA (2010) Diagnostic X-rays and risk of childhood leukemia. Int J Epidemiol. Dec;39(6):1628-37. PMID: 20889538. [PDF]

Rappaport SM, Smith MT (2010) Environment and disease risks. Science, Oct 22. 330(6003):460-1. PMID: 20966241. [PDF]

Rappaport SM, Smith MT (2010) Environment and disease risks. Science. Oct 22. In Press. [PDF]

Wiemels JL, Kang M, Chang JS, Zheng L, Kouyoumji C, Zhang L, Smith MT, Scelo G, Metayer C, Buffler P, Wiencke JK (2010) Backtracking RAS mutations in high hyperdiploid childhood acute lymphoblastic leukemia. Blood Cells Mol Dis. Oct 15;45(3):186-91. PMCID: PMC2943008. [PDF]

Ward EM, Schulte PA, Straif K, Hopf NB, Caldwell JC, Carreón T, Demarini DM, Fowler BA, Goldstein BD, Hemminki K, Hines CJ, Pursiainen KH, Kuempel E, Lewtas J, Lunn RM, Lynge E, McElvenny DM, Muhle H, Nakajima T, Robertson LW, Rothman N, Ruder AM, Schubauer-Berigan MK, Siemiatycki J, Silverman D, Smith MT, Sorahan T, Steenland K, Stevens RG, Vineis P, Zahm SH, Zeise L, Cogliano VJ (2010) Research recommendations for selected IARC-classified agents. Environ Health Perspect. Oct;118(10):1355-62. PMCID: PMC2957912. [PDF]

McHale, CM, Zhang L, Hubbard AE, Smith MT (2010) Toxicogenomic profiling of chemically exposed humans in risk assessment. Mutat Res. Apr 9. [Epub ahead of print]. PMCID: PMC2928857. [PDF]

Rappaport SM, Kim S, Lan Q, Li G, Vermeulen R, Waidyanatha S, Zhang L, Yin S, Smith MT and Rothman N (2010) Human benzene metabolism following occupational and environmental exposures. Chem Biol Interact, 184(1-2):189-95. PMID: 20026321 [PDF]

Smith MT (2010) Advances in understanding benzene health effects and susceptibility. Annu Rev Public Health. Apr 21; 31:133-48. PMID: 20070208. [PDF]

Zhang L, McHale CM, Rothman N, Li G, Ji Z, Vermeulen R, Hubbard AE, Ren X, Shen M, Rappaport SM, North M, Skibola CF, Yin S, Vulpe C, Chanock SJ, Smith MT, Lan Q (2010) Systems biology of human benzene exposure. Chem Biol Interact. Mar 19;184(1-2):86-93. PMID: 20026094. PMCID: PMC2846187. [PDF]

Lightfoot TJ, Roman E, Smith MT, Skibola CF (2010) Acute lymphoblastic leukaemia in children – is there a role for MTHFR? Br J Haematol. Feb 8 [Epub ahead of print]. PMID: 20148884. [PDF]

Vlaanderen J, Moore LE, Smith MT, Lan Q, Zhang L, Skibola CF, Rothman N, Vermeulen R (2010) Application of OMICS technologies in occupational and environmental health research; current status and projections. Occup Environ Med. Feb; 67(2):136-43. PMID: 19933307. [PDF]

Lightfoot TJ, Johnston WT, Painter D, Simpson J, Roman E, Skibola CF, Smith MT, Allan JM, Taylor GM (2010) Genetic variation in the folate metabolic pathway and risk of childhood leukemia. Blood. Jan 25; PMID: 20101025. [PDF]

2009

Whitehead T, Metayer C, Gunier RB, Ward MH, Nishioka MG, Buffler P, Rappaport SM (2009) Determinants of polycyclic aromatic hydrocarbon levels in house dust. J Expo Sci Environ Epidemiol. Dec 30. [Epub ahead of print] doi:10.1038/jes.2009.68. PMID: 20040932. [PDF]

Chang JS, Buffler PA, Metayer C, Chokkalingam AP, Patoka J, Kronish D, Wiemels JL (2009) Maternal immunoglobulin E and childhood leukemia. Cancer Epidemiol Biomarkers Prev. Aug; 18(8):2221-7. PMID: 19622720. [PDF]

Urayama KY, Von Behren J, Reynolds P, Hertz A, Does M, Buffler PA (2009) Factors associated with residential mobility in children with leukemia: implications for assigning exposures. Ann Epidemiol. Nov; 19(11):834-40. PMID: 19364662. PMCID: PMC2761989. [PDF]

Ward MH, Colt JS, Metayer C, Gunier RB, Lubin J, Crouse V, Nishioka MG, Reynolds P, Buffler PA (2009) Residential exposure to polychlorinated biphenyls and organochlorine pesticides and risk of childhood leukemia. Environ Health Perspect. Jun; 117(6):1007-13. PMID: 19590698. PMCID: PMC2702395. [PDF]

Whitehead T, Metayer C, Ward MH, Nishioka MG, Gunier R, Colt JS, Reynolds P, Selvin S, Buffler P, Rappaport SM (2009) Is house-dust nicotine a good surrogate for household smoking? Am J Epidemiol. May 1; 169(9):1113-23. PMID: 19299402. PMCID: PMC2727236. [PDF]

Scelo G, Metayer C, Zhang L, Wiemels JL, Aldrich MC, Selvin S, Month S, Smith MT, Buffler PA (2009) Household exposure to paint and petroleum solvents, chromosomal translocations, and the risk of childhood leukemia. Environ Health Perspect. Jan; 117(1):133-9. PMID: 19165400. PMCID: PMC2627857. [PDF]

2008

Guha N, Chang JS, Chokkalingam AP, Wiemels JL, Smith MT, Buffler PA (2008) NQO1 polymorphisms and de novo childhood leukemia: a HuGE review and meta-analysis. Am J Epidemiol. Dec 1; 168(11):1221-32. PMID: 18945694. PMCID: PMC2727266. [PDF]

Wiemels JL, Hofmann J, Kang M, Selzer R, Green R, Zhou M, Zhong S, Zhang L, Smith MT, Marsit C, Loh M, Buffler P, Yeh RF (2008) Chromosome 12p deletions in TEL-AML1 childhood acute lymphoblastic leukemia are associated with retrotransposon elements and occur postnatally. Cancer Res. Dec 1; 68(23):9935-44. PMID: 19047175. PMCID: PMC2597307. [PDF]

Vasconcelos GM, Kang M, Pombo-de-Oliveira MS, Schiffman JD, Lorey F, Buffler P, Wiemels JL (2008) Adenovirus detection in Guthrie cards from paediatric leukaemia cases and controls. Br J Cancer. Nov 18; 99(10):1668-72. PMID: 19002185. PMCID: PMC2584954. [PDF]

Rollison DE, Howlader N, Smith MT, Strom SS, Merritt WD, Ries LA, Edwards BK, List AF (2008) Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood. Jul 1; 112(1):45-52. PMID: 18443215. [PDF]

Metayer C, Buffler PA (2008) Residential exposures to pesticides and childhood leukaemia.Radiat Prot Dosimetry. 132(2):212-9. PMID: 18940823. [PDF]

Colt JS, Gunier RB, Metayer C, Nishioka MG, Bell EM, Reynolds P, Buffler PA, Ward MH (2008) Household vacuum cleaners vs. the high-volume surface sampler for collection of carpet dust samples in epidemiologic studies of children. Environ Health. 7:6. PMID: 18291036. PMCID: PMC2265689. [PDF]

2007

Chang JS, Metayer C, Fear NT, Reinier K, Yin X, Urayama K, Russo C, Jolly KW, Buffler PA (2007) Parental social contact in the work place and the risk of childhood acute lymphoblastic leukaemia. Br J Cancer. Nov 5; 97(9):1315-21. PMID: 17923868. PMCID: PMC2360459: [PDF]

Escobar PA, Smith MT, Vasishta A, Hubbard AE, Zhang L (2007) Leukaemia-specific chromosome damage detected by comet with fluorescence in situ hybridization (comet-FISH). Mutagenesis. Sep; 22(5):321-7. PMID: 17575318. [PDF]

Zhang L, Rothman N, Li G, Guo W, Yang W, Hubbard AE, Hayes RB, Yin S, Lu W, Smith MT (2007) Aberrations in chromosomes associated with lymphoma and therapy-related leukemia in benzene-exposed workers. Environ Mol Mutagen. Jul; 48(6):467-74. PMID: 17584886. [PDF]

Urayama KY, Wiencke JK, Buffler PA, Chokkalingam AP, Metayer C, Wiemels JL (2007) MDR1 gene variants, indoor insecticide exposure, and the risk of childhood acute lymphoblastic leukemia. Cancer Epidemiol Biomarkers Prev. Jun; 16(6):1172-7. PMID: 17548681. [PDF]

Hegedus CM, Skibola CF, Bracci P, Holly EA, Smith MT (2007) Screening the human serum proteome for genotype-phenotype associations: An analysis of the IL6 -174G>C polymorphism. Proteomics. Feb;7(4):548-57. PMID: 17309100. [PDF]

Kwan ML, Metayer C, Crouse V, Buffler PA (2007) Maternal illness and drug/medication use during the period surrounding pregnancy and risk of childhood leukemia among offspring.Am J Epidemiol. Jan 1; 165(1):27-35. PMID: 17035343. [PDF]

Lin YS, Vermeulen R, Tsai CH, Waidyanatha S, Lan Q, Rothman N, Smith MT, Zhang L, Shen M, Li G, Yin S, Kim S, Rappaport SM (2007) Albumin adducts of electrophilic benzene metabolites in benzene-exposed and control workers. Environ Health Perspect. Jan; 115(1):28-34. PMID: 17366815. PMCID: PMC1797829. [PDF]

Chen J, van der Laan MJ, Smith MT, Hubbard AE (2007) A comparison of methods to control type I errors in microarray studies. Stat Appl Genet Mol Biol. 6:Article28. PMID: 18052911. [PDF]

2006

Paynter RA, Skibola DR, Skibola CF, Buffler PA, Wiemels JL, Smith MT (2006) Accuracy of multiplexed Illumina platform-based single-nucleotide polymorphism genotyping compared between genomic and whole genome amplified DNA collected from multiple sources.Cancer Epidemiol Biomarkers Prev. Dec; 15(12):2533-6. PMID: 17164381. [PDF]

Chang JS, Selvin S, Metayer C, Crouse V, Golembesky A, Buffler PA (2006) Parental smoking and the risk of childhood leukemia. Am J Epidemiol. Jun 15; 163(12):1091-100. PMID: 16597704. [PDF]

Aldrich MC, Zhang L, Wiemels JL, Ma X, Loh ML, Metayer C, Selvin S, Feusner J, Smith MT, Buffler PA (2006) Cytogenetics of Hispanic and White children with acute lymphoblastic leukemia in California. Cancer Epidemiol Biomarkers Prev. Mar; 15(3):578-81. PMID: 16537719. [PDF]

Birkner MD, Hubbard AE, van der Laan MJ, Skibola CF, Hegedus CM, Smith MT (2006) Issues of processing and multiple testing of SELDI-TOF MS proteomic data. Stat Appl Genet Mol Biol. 5:Article11. PMID: 16646865. [PDF]

2005

Hegedus CM, Gunn L, Skibola CF, Zhang L, Shiao R, Fu S, Dalmasso EA, Metayer C, Dahl GV, Buffler PA, Smith MT (2005) Proteomic analysis of childhood leukemia. Leukemia. Oct; 19(10):1713-8. PMID: 16136170. [PDF]

Smith MT, McHale CM, Wiemels JL, Zhang L, Wiencke JK, Zheng S, Gunn L, Skibola CF, Ma X, Buffler PA (2005) Molecular biomarkers for the study of childhood leukemia. Toxicol Appl Pharmacol. Aug 7; 206(2):237-45. PMID: 15967214. [PDF]

Rappaport SM, Waidyanatha S, Yeowell-O’Connell K, Rothman N, Smith MT, Zhang L, Qu Q, Shore R, Li G, Yin S (2005) Protein adducts as biomarkers of human benzene metabolism.Chem Biol Interact. May 30; 153-154(103-9. PMID: 15935805. [PDF]

Zhang L, Yang W, Hubbard AE, Smith MT (2005) Nonrandom aneuploidy of chromosomes 1, 5, 6, 7, 8, 9, 11, 12, and 21 induced by the benzene metabolites hydroquinone and benzenetriol. Environ Mol Mutagen. May; 45(4):388-96. PMID: 15662717. [PDF]

Wiemels JL, Zhang Y, Chang J, Zheng S, Metayer C, Zhang L, Smith MT, Ma X, Selvin S, Buffler PA, Wiencke JK (2005) RAS mutation is associated with hyperdiploidy and parental characteristics in pediatric acute lymphoblastic leukemia. Leukemia. Mar; 19(3):415-9. PMID: 15674422. [PDF]

Buffler PA, Kwan ML, Reynolds P, Urayama KY (2005) Environmental and genetic risk factors for childhood leukemia: appraising the evidence. Cancer Invest. 23(1):60-75. PMID: 15779869. [PDF]

Book Chapters

Gunn L, Zhang L, Smith MT (2005) Novel biomarkers: New methods for assessing acquired DNA damage in humans without cancer. Cancer Risk Assessment, edited by Shields PG. Chapter 5, pp77-97.