Philip Lazarus, Ph.D.

Ph.D., McGill University, Montreal, Quebec, Canada; Experimental Medicine

Bachelor of Science, McGill University, Montreal, Quebec, Canada; Human Genetics

Fellowships & Additional Training
Postdoctoral Fellowship, McGill University, Montreal, Quebec, Canada; Biochemistry

Dr. Philip Lazarus’ research is focused on the elucidation of carcinogenic mechanisms with an underlying theme of cancer prevention, focusing primarily on mechanisms involved in the induction and progression of tobacco-related cancers. As the major risk factor for aerodigestive tract cancer induction is the use of tobacco products, a major focus has been the study of tobacco carcinogen metabolism and the identification of biochemical and molecular markers of tobacco-induced carcinogenesis.

On-going studies include the following:
A. Molecular epidemiologic studies examining genetic and phenotypic polymorphisms in xenobiotic-metabolizing enzyme as well as DNA repair genes as markers for cancer risk. The carcinogenic activity of tobacco carcinogens can often depend on the cellular composition/expression/activity of enzymes that are involved in the activation or detoxification of many tobacco carcinogens or the repair of the DNA adducts they induce. The expression and/or activity of these enzymes may be a critical determinant of individual risk for tobacco carcinogen-induced damage. Studies from Lazarus' laboratory have identified function/expression-altering genetic polymorphisms for a number of these enzymes, and have shown that they may play a role in increased risk for certain cancers. Current studies are focused upon the identification of high-risk genotypes important in risk for other cancers including colon, esophageal and breast cancer, identification of novel chemoprevention agents, and enzyme promoter characterization and induction mechanisms.

B. Studies characterizing carcinogen metabolic pathways and examining their role in cancer susceptibility. Studies have focused on enzyme pathways involved in the detoxification of the potent carcinogens benzo(a)pyrene and NNK.

C. Studies are on-going examining a novel mechanism of regulation of the p53 tumor suppressor protein. Recent studies from Dr. Lazarus' lab have demonstrated that a novel transcription-coupled translational control mechanism appears to play a role in regulating p53 protein synthesis in normal versus tumor tissues. These studies suggest that this novel translational control mechanism may play an important role in the up-regulation of p53 protein expression observed upon cellular insult or tumor initiation. Current studies have focused upon the characterization of this novel regulatory mechanism.

Publications since 2013
Ashmore J, Gallagher CJ, Lesko SM, Muscat JE, Hartman T, Lazarus P. No association between vitamin D intake, VDR polymorphisms, and colorectal cancer in a population-based case-control study. Cancer Epidemiol Biomarkers Prev (accepted upon revision).

Gufford BT, Chen G, Lazarus P, Oberlies NH, Paine MF. Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: a Potential Clinically Relevant Natural Product-Drug Interaction. Drug Metabol Dispos (In press).

McGrath-Morrow SA, Hayashi M, Aherrera A, Lopez A, Malinina A, Collaco JM, Neptune E, Klein JD, Winickoff JP, Breysse P, Lazarus P, Chen G. The effects of E-cigarette exposure on systemic cotinine levels and postnatal lung growth in neonatal mice. PlosOne 2015; Feb 23;10(2):e0118344. PMID:25706869

Modesto JL, Hull A, Angstadt A, Berg A, Gallagher CJ, Lazarus P and Muscat JE. NNK reduction pathway gene polymorphisms and risk of lung cancer. Mol Carcinogen. 2015; Jun 29. [Epub ahead of print] PMID: 24976539

Chen L-S, Hung R, Baker T, Horton A, Culverhouse R, Saccone N, Cheng I, Deng B, Han Y, Hansen H, Horsman J, Kim C, Lutz S, Rosenberger A, Aben K, Andrew A, Naomi B, Chang S-C, Dieffenbach A, Dienemann H, Frederiksen B, Han J, Hatsukami D, Johnson E, Pande M, Wrensch M, McLaughlin J, Skaug V, van der Heijden E, Wampfler J, Wenzlaff A, Woll P, Zienolddiny S, Bickeböller H, Brenner H, Duell E, Haugen A, Heinrich J, Hokanson J, Hunter D, Kiemeney L, Lazarus P, Le Marchand L, Liu G, Mayordomo J, Risch A, Schwartz A, Teare MD, Wu X, Wiencke J, Yang P, Zhang Z-F, Spitz M, Kraft P, Amos C, and Bierut L. CHRNA5 Risk Variant Predicts Delayed Smoking Cessation and Earlier Lung Cancer Diagnosis - A Meta-analysis. J Natl Cancer Inst 2015 Apr 14;107(5) (In press). PMID: 25873736

Toporcov TN, Znaor A, Zhang Z-F, Yu G-P, Winn DM, Wei Q, Vilensky M, Vaughan T, Thomson P, Talamini R, Szeszenia-Dabrowska N, Sturgis EM, Smith E, Shangina O, Schwartz SM, Schantz S, Rudnai P, Richiardi L, Ramroth HM, Purdue MP, Olshan AF, Eluf-Neto J, Muscat JE, Moyses RA, Morgenstern H, Menezes A, McClean M, Matsuo K, Mates D, Macfarlane TV, Lissowska J, Levi F, Lazarus P, La Vecchia C, Lagiou P, Koifman S, Kjaerheim K, Kelsey K, Holcatova I, Herrero R, Healy C, Hayes RB, Franceschi S, Fernandez L, Fabianova E, Daudt AW, Dal Maso L, Curioni OA, Curado MP, Conway D, Chen C, Castellsague X, Canova C, Cadoni G, Brennan P, Boccia S, Antunes JLF, Antunes F, Ahrens W, Agudo A, Boffetta P, Hashibe M, Lee Y-CA, Filho VW. Risk factors for head and neck cancer in young adults: A pooled analysis in the INHANCE consortium. Int J Epidemiol. 2015; 44(1):169-85. PMID: 25613428

Zhang LR, Morgenstern H, Greenland S, Chang S-C, Lazarus P, Teare MD, Woll PJ, Orlow I, Cox B on behalf of the Cannabis and Respiratory Disease Research Group of New Zealand, Brhane Y, Liu G, Hung RJ. Cannabis smoking and lung cancer risk: pooled analysis in the International Lung Cancer Consortium. Int J Cancer. 2015; 136(4):894-903. PMID: 24947688

Conway DI and 73 others including Lazarus P. Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries. Int J Cancer. Int J Cancer. 2015; 136(5):1125-39. PMID: 24996155

Gufford BT, Lazarus P, Oberlies NH, Paine MF. Predicting Pharmacokinetic Herb-Drug Interactions: Overcoming Hurdles that Extend beyond Drug-Drug Interactions. Amer Assoc Pharm Soc (NewsMagazine) April 14 2014; pp. 18-22.

Menvielle G, Truong T, Jellouli F, Stücker I, Brenner H, Field JK, Hosgood HD, Lan Q, Landi MT, Hung RJ, Lazarus P, McLaughlin J, Morgenstern H, Muscat JE, Ruano-Ravina A, Schwartz AG, Seow A, Spitz MR, Tardon A, Zhang ZF, Luce D. Education and lung cancer among never smokers. Epidemiology. 2014; 25(6):934-5. PMID: 25265142

Gufford BT, Chen G, Lazarus P, Graf TN, Oberlies NH, Paine MF. Identification of Diet-Derived Constituents as Potent Inhibitors of Intestinal Glucuronidation Drug Metab Dispos. 2014; 42(10):1675-83. PMID: 25008344

Kim CH, Amy Lee YC, Hung RJ, McNallan SR, Cote ML, Lim WY, Chang SC, Kim JH, Ugolini D, Chen Y, Liloglou T, Andrew AS, Onega T, Duell EJ, Field JK, Lazarus P, Marchand LL, Neri M, Vineis P, Kiyohara C, Hong YC, Morgenstern H, Matsuo K, Tajima K, Christiani DC, McLaughlin JR, Bencko V, Holcatova I, Boffetta P, Brennan P, Fabianova E, Foretova L, Janout V, Lissowska J, Mates D, Rudnai P, Szeszenia-Dabrowska N, Mukeria A, Zaridze D, Seow A, Schwartz AG, Yang P, Zhang ZF. Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO). Int J Cancer. 2014; 135(8):1918-30. PMID: 24615328

Angstadt AY, Zhu J, Muscat JE, Hartman TJ, Lesko SM, Gallagher CJ, Lazarus P. The effect of UGT1A and UGT2B polymorphisms on colorectal cancer risk: haplotype associations and gene-environment interactions. Genes Chrom Cancer. 2014; 53(6):454-66. PMID: 24822274.

Jones NR, Lazarus P. UGT2B gene expression analysis and identification of stably-expressed control genes for use in real-time PCR in multiple organ sites. Drug Metabol Dispos. 2014; 42(4):529-36. PMID: 24459179

Dluzen DF, Sun D, Salzberg AC, Jones N, Bushey RT, Robertson GP, Lazarus P. Regulation of UGT1A1 expression and activity by miR-491-3p. J Pharmacol Exper Ther. 2014; 348(3):465-77. PMID: 24399855

Marks MA, Chaturvedi AK, Kelsey K, Straif K, Berthiller J, Schwartz SM, Smith E, Wyss A, Brennan P, Olshan AF, Wei Q, Sturgis EM, Zhang ZF, Morgenstern H, Muscat J, Lazarus P, McClean M, Chen C, Vaughan TL, Wunsch-Filho V, Curado MP, Koifman S, Matos E, Menezes A, Daudt AW, Fernandez L, Posner M, Boffetta P, Lee YC, Hashibe M, D'Souza G. Cancer Epidemiol Biomarkers Prev. 2014; 23(1):160-71. PMID: 24351902

Baldwin DA, Sarnowski CP, Reddy SA, Blair IA, Clapper M, Lazarus P, Li M, Muscat JE, Penning TM, Vachani A, Whitehead AS. Development of a genotyping microarray for studying the role of gene-environment interactions in risk for lung cancer. J Biomol Tech. 2013 Dec;24(4):198-217. doi: 10.7171/jbt.13-2404-004. PMID: 24294113

Leoncini E, Ricciardi W, Cadoni G, Arzani D, Petrelli L, Paludetti G, Brennan P, Luce D, Stucker I, Matsuo K, Talamini R, La Vecchia C, Olshan AF, Winn DM, Herrero R, Franceschi S, Castellsague X, Muscat J, Morgenstern H, Zhang ZF, Levi F, Dal Maso L, Kelsey K, McClean M, Vaughan TL, Lazarus P, Purdue MP, Hayes RB, Chen C, Schwartz SM, Shangina O, Koifman S, Ahrens W, Matos E, Lagiou P, Lissowska J, Szeszenia-Dabrowska N, Fernandez L, Menezes A, Agudo A, Daudt AW, Richiardi L, Kjaerheim K, Mates D, Betka J, Yu GP, Schantz S, Simonato L, Brenner H, Conway DI, Macfarlane TV, Thomson P, Fabianova E, Znaor A, Rudnai P, Healy C, Boffetta P, Chuang SC, Lee YC, Hashibe M, Boccia S. Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium. Eur J Epidemiol. 2014; 29(1):35-48. PMID: 24271556

Ashmore JH, Lesko SM, Muscat JE, Gallagher CJ, Berg AS, Miller PE, Hartman TJ, Lazarus P. Association of Dietary and Supplemental Folate Intake and Polymorphisms in Three FOCM Pathway Genes with Colorectal Cancer in a Population-Based Case-Control Study. Genes Chrom Cancer 2013; 52(10):945-53. PMID: 23893618

Ashmore JH, Lesko SM, Miller PE, Cross AJ, Muscat JE, Zhu J, Liao J, Harper G, Lazarus P, Hartman TJ. 2013. Association of dietary and supplemental iron and colorectal cancer in a population-based study. Eur J Cancer Prev. 2013; Mar 12. [Epub ahead of print].

Wyss A and 45 others including Lazarus P. Cigarette, cigar, and pipe smoking and the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Amer J Epidemiol. 2013; 178(5):679-90. PMID: 23817919

Angstadt AY, Berg AS, Zhu J, Hartman TJ, Lesko SM, Muscat JE, Lazarus P, Gallagher CJ. The effect of copy number variation (CNV) in the phase II detoxification genes, UGT2B17 and UGT2B28, on colorectal cancer risk. Cancer. 2013; 119(13):2477-85. PMID: 23575887

Angstadt AY, Berg AS, Zhu J, Hartman TJ, Lesko SM, Muscat JE, Lazarus P, Gallagher CJ. The effect of copy number variation (CNV) in the phase II detoxification genes, UGT2B17 and UGT2B28, on colorectal cancer risk. Cancer. 2013; 119(13):2477-85. PMID: 23575887

Miller PE, Lazarus P, Lesko SM, Cross AJ, Sinha R, Laio J, Zhu J, Harper G, Muscat JE, Hartman TJ. Meat-Related Compounds and Colorectal Cancer Risk by Anatomical Subsite. Nutr Cancer. 2013; 65(2):202-26. PMID: 23441608

Bushey RT, Dluzen DF, Lazarus P. Importance of UDP-glucuronosyltransferases 2A2 and 2A3 in tobacco carcinogen metabolism. Drug Metab Dispos. 2013; 41(1):170-9. PMID: 23086198

Nichenametla SN, Muscat JE, Liao JG, Lazarus P, Richie JP Jr. A functional trinucleotide repeat polymorphism in the 5'-untranslated region of the glutathione biosynthetic gene GCLC is associated with increased risk for lung and aerodigestive tract cancers. Mol Carcinogen. 2013; 52(10):791-9. PMID: 22610501

More Publications


NIH R01 CA164366-01A1 (Lazarus, Philip); 2012-2017
“Role of Pharmacogenetics on Exemestane Metabolism and Toxicity” This is a collaborative study with Queens Unversity (Kingston, ON), Penn State University (Hershey, PA) and Harvard University (Boston, MA) to fully characterize the metabolism of the aromatase inhibitor, exemestane (commonly used for the treatment and prevention of breast cancer), and to explore the effects, both in vitro and in vivo, of polymorphisms that occur in enzymes that mediate exemestane metabolic reactions.

NIH R01 ES025460 (Lazarus, Philip); July 2015- June 2020 (Pending) “The UGT2A and 3A metabolizing enzymes and tobacco-related cancer risk” The goal of this proposal is to examine the role of two previously under-studied phase II metabolizing enzyme sub-families (UGT2A and UGT3A) on drug response and cancer risk.

Recent Presentations and Invited Seminars
1. Seminar, Dept of Pharmacology and Toxicology, College of Medicine, University of Toronto, Toronto, Canada April 2015

2. Markey Cancer Center, University of Kentucky. ‘Characterization and Regulation of Tobacco Carcinogen and Nicotine Metabolism Pathways: Potential for Smoking Cessation Drug Targeting’

3. "Potential Effects on Drug–Drug Interactions and Disease Susceptibility by Regulation of UGT Activity/Expression via Epigenetic Mechanisms (miRNA) and Alternate Splicing" presented at the Translation of Preclinical Drug–Drug Interaction and Metabolism Data into Risk Assessment of Clinical Toxicity symposium at the New York Academy of Sciences Conference Center in New York City. October 21, 2013

Meetings Attended
1. International Lung Cancer Consortium (ILCCO) meeting, New York City, NY; May 2015

2. International Head and Neck Cancer Consortium (INHANCE) meeting, New York City, NY; May 2015

updated 06/18/2015     Back to top
photo of Dr. Philip Lazarus

Chair and
Boeing Distinguished Professor

Pharmaceutical Sciences

Office: PBS 431
P.O. Box 1495
Washington State University
Spokane, WA  99210-1495