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Grant Details

Grant Number: 5R01CA098380-05 Interpret this number
Primary Investigator: Li, Donghui
Organization: Ut Md Anderson Cancer Ctr
Project Title: Molecular Epidemiology of Pancreatic Cancer
Fiscal Year: 2008
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Abstract

DESCRIPTION (provided by applicant): Pancreatic cancer contributes 5% of the total cancer death in this country. It is a deadly disease but the etiology is poorly understood. Our long-term goal is to identify genetic and environmental factors that contribute to pancreatic cancer so novel preventive strategies can be developed. With an NCI grant support (RO3 CA84581), we have conducted a pilot hospital-based case-control study of pancreatic cancer. We have found a significant association between dietary exposure of heterocyclic aromatic amines (HCA) and increased risk of pancreatic cancer. We have also observed significant interactions of a number of drug-metabolizing genes and a DNA repair gene with smoking and HCA exposure. Furthermore we have detected a significantly higher frequency of micronucleus (MN) in peripheral lymphocytes of cancer cases compared to that of controls. The current proposal will build upon these results to further test the hypothesis that carcinogen exposure through smoking and dietary HCA intake increases the risk of pancreatic cancer, especially among genetically susceptible individuals. We will test this hypothesis in a hospital-based case control study with 400 cases of newly diagnosed pancreatic adenocarcinomas and 400 frequency-matched healthy controls. Cases and controls will be matched by gender, race, and age (+/- 5 years) and will be recruited from the UT M.D. Anderson Cancer Center. To identify the high-risk exposure group, we will assess the risk factor and exposure profile by using a risk factor questionnaire, a meat preparation questionnaire, and a food frequency questionnaire to collect information on smoking, alcohol, medical history, family history of cancer, and dietary history. Exposure levels of three major dietary HCA compounds as well as total HCAs will be determined in relation to cancer risk. We will determine genetic susceptibility to HCA exposure and smoking by examining the polymorphisms of several metabolic genes, i.e. CYP1A2, CYP1B1, CYP2E1, NAT1, NAT2, SUL1A1, UGT1A1 and GSTT1, and a DNA repair gene, XRCCI. We will measure the level of ENU-induced DNA adducts and frequency of MN in peripheral lymphocytes of each study participants. These biological measurements will be analyzed in relation to disease status and exposure history. Results of this study are expected to shed light on the rote of carcinogen exposure and genetic susceptibility to such exposure in the development of pancreatic cancer. Such information will be valuable for the primary prevention of this deadly disease.

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Publications

Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene- and pathway-based interaction analysis of GWAS data.
Authors: Tang H, Wei P, Duell EJ, Risch HA, Olson SH, Bueno-de-Mesquita HB, Gallinger S, Holly EA, Petersen G, Bracci PM, McWilliams RR, Jenab M, Riboli E, Tjønneland A, Boutron-Ruault MC, Kaaks R, Trichopoulos D, Panico S, Sund M, Peeters PH, Khaw KT, Amos CI, Li D
Source: Carcinogenesis, 2014 May;35(5), p. 1039-45.
EPub date: 2014 Jan 13.
PMID: 24419231
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Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis.
Authors: Tang H, Wei P, Duell EJ, Risch HA, Olson SH, Bueno-de-Mesquita HB, Gallinger S, Holly EA, Petersen GM, Bracci PM, McWilliams RR, Jenab M, Riboli E, Tjønneland A, Boutron-Ruault MC, Kaaks R, Trichopoulos D, Panico S, Sund M, Peeters PH, Khaw KT, Amos CI, Li D
Source: Cancer Epidemiol Biomarkers Prev, 2014 Jan;23(1), p. 98-106.
EPub date: 2013 Oct 17.
PMID: 24136929
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An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population.
Authors: Klein AP, Lindström S, Mendelsohn JB, Steplowski E, Arslan AA, Bueno-de-Mesquita HB, Fuchs CS, Gallinger S, Gross M, Helzlsouer K, Holly EA, Jacobs EJ, Lacroix A, Li D, Mandelson MT, Olson SH, Petersen GM, Risch HA, Stolzenberg-Solomon RZ, Zheng W, Amundadottir L, Albanes D, Allen NE, Bamlet WR, Boutron-Ruault MC, Buring JE, Bracci PM, Canzian F, Clipp S, Cotterchio M, Duell EJ, Elena J, Gaziano JM, Giovannucci EL, Goggins M, Hallmans G, Hassan M, Hutchinson A, Hunter DJ, Kooperberg C, Kurtz RC, Liu S, Overvad K, Palli D, Patel AV, Rabe KG, Shu XO, Slimani N, Tobias GS, Trichopoulos D, Van Den Eeden SK, Vineis P, Virtamo J, Wactawski-Wende J, Wolpin BM, Yu H, Yu K, Zeleniuch-Jacquotte A, Chanock SJ, Hoover RN, Hartge P, Kraft P
Source: PLoS One, 2013;8(9), p. e72311.
EPub date: 2013 Sep 13.
PMID: 24058443
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Association of diabetes and perineural invasion in pancreatic cancer.
Authors: Sahin IH, Shama MA, Tanaka M, Abbruzzese JL, Curley SA, Hassan M, Li D
Source: Cancer Med, 2012 Dec;1(3), p. 357-62.
EPub date: 2012 Oct 30.
PMID: 23342285
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Insights into pancreatic cancer etiology from pathway analysis of genome-wide association study data.
Authors: Wei P, Tang H, Li D
Source: PLoS One, 2012;7(10), p. e46887.
EPub date: 2012 Oct 4.
PMID: 23056513
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Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).
Authors: Duell EJ, Lucenteforte E, Olson SH, Bracci PM, Li D, Risch HA, Silverman DT, Ji BT, Gallinger S, Holly EA, Fontham EH, Maisonneuve P, Bueno-de-Mesquita HB, Ghadirian P, Kurtz RC, Ludwig E, Yu H, Lowenfels AB, Seminara D, Petersen GM, La Vecchia C, Boffetta P
Source: Ann Oncol, 2012 Nov;23(11), p. 2964-70.
EPub date: 2012 Jul 5.
PMID: 22767586
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Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer.
Authors: Li D, Duell EJ, Yu K, Risch HA, Olson SH, Kooperberg C, Wolpin BM, Jiao L, Dong X, Wheeler B, Arslan AA, Bueno-de-Mesquita HB, Fuchs CS, Gallinger S, Gross M, Hartge P, Hoover RN, Holly EA, Jacobs EJ, Klein AP, LaCroix A, Mandelson MT, Petersen G, Zheng W, Agalliu I, Albanes D, Boutron-Ruault MC, Bracci PM, Buring JE, Canzian F, Chang K, Chanock SJ, Cotterchio M, Gaziano JM, Giovannucci EL, Goggins M, Hallmans G, Hankinson SE, Hoffman Bolton JA, Hunter DJ, Hutchinson A, Jacobs KB, Jenab M, Khaw KT, Kraft P, Krogh V, Kurtz RC, McWilliams RR, Mendelsohn JB, Patel AV, Rabe KG, Riboli E, Shu XO, Tjønneland A, Tobias GS, Trichopoulos D, Virtamo J, Visvanathan K, Watters J, Yu H, Zeleniuch-Jacquotte A, Amundadottir L, Stolzenberg-Solomon RZ
Source: Carcinogenesis, 2012 Jul;33(7), p. 1384-90.
EPub date: 2012 Apr 20.
PMID: 22523087
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Metformin use is associated with better survival of diabetic patients with pancreatic cancer.
Authors: Sadeghi N, Abbruzzese JL, Yeung SC, Hassan M, Li D
Source: Clin Cancer Res, 2012 May 15;18(10), p. 2905-12.
EPub date: 2012 Mar 31.
PMID: 22465831
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Diabetes and risk of pancreatic cancer: a pooled analysis of three large case-control studies.
Authors: Li D, Tang H, Hassan MM, Holly EA, Bracci PM, Silverman DT
Source: Cancer Causes Control, 2011 Feb;22(2), p. 189-97.
EPub date: 2010 Nov 21.
PMID: 21104117
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Micronuclei levels in peripheral blood lymphocytes as a potential biomarker for pancreatic cancer risk.
Authors: Chang P, Li Y, Li D
Source: Carcinogenesis, 2011 Feb;32(2), p. 210-5.
EPub date: 2010 Nov 19.
PMID: 21097528
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New strategies in pancreatic cancer: emerging epidemiologic and therapeutic concepts.
Authors: Li D, Abbruzzese JL
Source: Clin Cancer Res, 2010 Sep 1;16(17), p. 4313-8.
EPub date: 2010 Jul 20.
PMID: 20647474
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Antioxidant genes, diabetes and dietary antioxidants in association with risk of pancreatic cancer.
Authors: Tang H, Dong X, Day RS, Hassan MM, Li D
Source: Carcinogenesis, 2010 Apr;31(4), p. 607-13.
EPub date: 2010 Jan 22.
PMID: 20097730
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Pancreatitis and pancreatic cancer in two large pooled case-control studies.
Authors: Bracci PM, Wang F, Hassan MM, Gupta S, Li D, Holly EA
Source: Cancer Causes Control, 2009 Nov;20(9), p. 1723-1731.
PMID: 19760029
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Body mass index and risk, age of onset, and survival in patients with pancreatic cancer.
Authors: Li D, Morris JS, Liu J, Hassan MM, Day RS, Bondy ML, Abbruzzese JL
Source: JAMA, 2009 Jun 24;301(24), p. 2553-62.
PMID: 19549972
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Antidiabetic therapies affect risk of pancreatic cancer.
Authors: Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL
Source: Gastroenterology, 2009 Aug;137(2), p. 482-8.
EPub date: 2009 Apr 16.
PMID: 19375425
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DNA repair gene polymorphisms and risk of pancreatic cancer.
Authors: Li D, Suzuki H, Liu B, Morris J, Liu J, Okazaki T, Li Y, Chang P, Abbruzzese JL
Source: Clin Cancer Res, 2009 Jan 15;15(2), p. 740-6.
PMID: 19147782
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Effect of insulin-like growth factor gene polymorphisms alone or in interaction with diabetes on the risk of pancreatic cancer.
Authors: Suzuki H, Li Y, Dong X, Hassan MM, Abbruzzese JL, Li D
Source: Cancer Epidemiol Biomarkers Prev, 2008 Dec;17(12), p. 3467-73.
PMID: 19064563
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Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer.
Authors: Suzuki H, Morris JS, Li Y, Doll MA, Hein DW, Liu J, Jiao L, Hassan MM, Day RS, Bondy ML, Abbruzzese JL, Li D
Source: Carcinogenesis, 2008 Jun;29(6), p. 1184-91.
EPub date: 2008 May 21.
PMID: 18499698
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Haplotype of N-acetyltransferase 1 and 2 and risk of pancreatic cancer.
Authors: Jiao L, Doll MA, Hein DW, Bondy ML, Hassan MM, Hixson JE, Abbruzzese JL, Li D
Source: Cancer Epidemiol Biomarkers Prev, 2007 Nov;16(11), p. 2379-86.
PMID: 18006927
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XRCC2 and XRCC3 gene polymorphism and risk of pancreatic cancer.
Authors: Jiao L, Hassan MM, Bondy ML, Wolff RA, Evans DB, Abbruzzese JL, Li D
Source: Am J Gastroenterol, 2008 Feb;103(2), p. 360-7.
EPub date: 2007 Nov 6.
PMID: 17986315
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Risk factors for pancreatic cancer: case-control study.
Authors: Hassan MM, Bondy ML, Wolff RA, Abbruzzese JL, Vauthey JN, Pisters PW, Evans DB, Khan R, Chou TH, Lenzi R, Jiao L, Li D
Source: Am J Gastroenterol, 2007 Dec;102(12), p. 2696-707.
EPub date: 2007 Aug 31.
PMID: 17764494
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Dietary mutagen exposure and risk of pancreatic cancer.
Authors: Li D, Day RS, Bondy ML, Sinha R, Nguyen NT, Evans DB, Abbruzzese JL, Hassan MM
Source: Cancer Epidemiol Biomarkers Prev, 2007 Apr;16(4), p. 655-61.
PMID: 17416754
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Glutathione S-transferase gene polymorphisms and risk and survival of pancreatic cancer.
Authors: Jiao L, Bondy ML, Hassan MM, Chang DZ, Abbruzzese JL, Evans DB, Smolensky MH, Li D
Source: Cancer, 2007 Mar 1;109(5), p. 840-8.
PMID: 17265526
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K-ras mutation and p16 and preproenkephalin promoter hypermethylation in plasma DNA of pancreatic cancer patients: in relation to cigarette smoking.
Authors: Jiao L, Zhu J, Hassan MM, Evans DB, Abbruzzese JL, Li D
Source: Pancreas, 2007 Jan;34(1), p. 55-62.
PMID: 17198183
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Polymorphisms of phase II xenobiotic-metabolizing and DNA repair genes and in vitro N-ethyl-N-nitrosourea-induced O6-ethylguanine levels in human lymphocytes.
Authors: Jiao L, Chang P, Firozi PF, Lai D, Abbruzzese JL, Li D
Source: Mutat Res, 2007 Mar 5;627(2), p. 146-57.
EPub date: 2006 Dec 8.
PMID: 17158087
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Detection of 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP)-DNA adducts in human pancreatic tissues.
Authors: Zhu J, Rashid A, Cleary K, Abbruzzese JL, Friess H, Takahashi S, Shirai T, Li D
Source: Biomarkers, 2006 Jul-Aug;11(4), p. 319-28.
PMID: 16908439
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The XPD Asp312Asn and Lys751Gln polymorphisms, corresponding haplotype, and pancreatic cancer risk.
Authors: Jiao L, Hassan MM, Bondy ML, Abbruzzese JL, Evans DB, Li D
Source: Cancer Lett, 2007 Jan 8;245(1-2), p. 61-8.
EPub date: 2006 Feb 3.
PMID: 16458430
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Polymorphisms of cytochrome P4501A2 and N-acetyltransferase genes, smoking, and risk of pancreatic cancer.
Authors: Li D, Jiao L, Li Y, Doll MA, Hein DW, Bondy ML, Evans DB, Wolff RA, Lenzi R, Pisters PW, Abbruzzese JL, Hassan MM
Source: Carcinogenesis, 2006 Jan;27(1), p. 103-11.
EPub date: 2005 Jun 29.
PMID: 15987714
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Direct tandem mass spectrometry reveals limitations in protein profiling experiments for plasma biomarker discovery.
Authors: Koomen JM, Li D, Xiao LC, Liu TC, Coombes KR, Abbruzzese J, Kobayashi R
Source: J Proteome Res, 2005 May-Jun;4(3), p. 972-81.
PMID: 15952745
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5,10-Methylenetetrahydrofolate reductase polymorphisms and the risk of pancreatic cancer.
Authors: Li D, Ahmed M, Li Y, Jiao L, Chou TH, Wolff RA, Lenzi R, Evans DB, Bondy ML, Pisters PW, Abbruzzese JL, Hassan MM
Source: Cancer Epidemiol Biomarkers Prev, 2005 Jun;14(6), p. 1470-6.
PMID: 15941958
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