Molecular Epidemiology of Pancreatic Cancer

胰腺癌的分子流行病学

• 批准号: 7425101
• 负责人: Donghui Li
• 金额: $ 102.02万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7425101
• 关键词: Age; Alcohol consumption; Alcohols; Aromatic Amines; Base Excision Repairs; Biological; Blood; Blood specimen; CYP1A2 gene; CYP1B1 gene; CYP2E1 gene; Cancer Center; Cancer Etiology; Carcinogen Metabolism; Carcinogen exposure; Carcinogens; Case-Control Studies; Cessation of life; Chromosomal Instability; Chromosomes; Companions; Consumption; Country; DNA Adducts; DNA Repair Gene; Development; Diabetes Mellitus; Dietary History; Disease; Doctor of Medicine; Drug Metabolic Detoxication; Environmental Risk Factor; Epidemiologic Studies; Ethylnitrosourea; Etiology; Family Cancer History; Family history of; Food; Frequencies; Friends; GSTT1 gene; GSTT1 protein; Gender; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genotype; Goals; Grant; Hospitals; Human; In Vitro; Incidence; Individual; Intake; Interview; Light; Lymphocyte; Malignant Neoplasms; Malignant neoplasm of pancreas; Measurement; Measures; Meat; Metabolic; Methods; Molecular Epidemiology; NAT2 gene; Newly Diagnosed; Numbers; Oxidative Stress; Pancreatic Adenocarcinoma; Participant; Patients; Peripheral; Pharmaceutical Preparations; Phenotype; Pilot Projects; Predisposition; Preparation; Prevention strategy; Primary Prevention; Questionnaires; Race; Rate; Recording of previous events; Recruitment Activity; Relative (related person); Risk; Risk Factors; Role; Smoker; Smoking; Testing; UDP-Glucuronosyltransferase 1A1; UGT1A1 gene; United States; University of Texas M D Anderson Cancer Center; Woman; XRCC1 gene; base; cancer risk; case control; cigarette smoking; food preparation; gene interaction; heterocyclic aromatic amines; men; micronucleus; mortality; non-smoking; novel

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.

描述（由申请人提供）：胰腺癌占该国癌症总死亡的5％。这是一种致命的疾病，但病因却很少理解。我们的长期目标是确定导致胰腺癌的遗传和环境因素，因此可以开发新的预防策略。在NCI赠款支持（RO3 CA84581）的情况下，我们进行了基于医院的试验性病例对照胰腺癌研究。我们发现杂环芳香胺（HCA）的饮食暴露与胰腺癌风险增加之间存在显着关联。我们还观察到许多药物代谢基因和吸烟和HCA暴露的DNA修复基因的显着相互作用。此外，与对照组相比，我们已经检测到癌症病例外周淋巴细胞中微核（MN）的频率明显更高。当前的建议将基于这些结果，以进一步检验以下假设：通过吸烟和饮食HCA摄入量暴露致癌物会增加患胰腺癌的风险，尤其是在遗传易感的个体中。我们将在一项基于医院的病例对照研究中检验这一假设，其中有400例新诊断的胰腺腺癌和400个频率匹配的健康对照组。案件和控制将与性别，种族和年龄（+/- 5年）相匹配，并将从UT M.D. Anderson癌症中心招募。为了确定高风险暴露组，我们将通过使用危险因素问卷，肉类制备问卷和一份食品频率问卷来评估风险因素和暴露概况，以收集有关吸烟，酒精，病史，癌症家族史和饮食史的信息。三种主要饮食HCA化合物以及总HCA的暴露水平将与癌症风险有关。我们将通过检查几种代谢基因的多态性，即CYP1A2，CYP1B1，CYP2E1，NAT1，NAT2，SUL1A1，UGT1A1和GSTT1，以及一个DNA修复基因，XRCCI，确定对HCA暴露和吸烟的遗传敏感性。我们将测量每个研究参与者的外周淋巴细胞中ENU诱导的DNA加合物的水平和MN的频率。这些生物测量将与疾病状况和暴露史有关。这项研究的结果预计将阐明致癌物暴露的死记硬背以及胰腺癌发展中这种暴露的遗传敏感性。此类信息对于主要预防这种致命疾病很有价值。

项目成果

Functional logistic regression approach to detecting gene by longitudinal environmental exposure interaction in a case-control study.

• DOI: 10.1002/gepi.21852
• 发表时间: 2014-11
• 期刊: GENETIC EPIDEMIOLOGY
• 影响因子: 2.1
• 作者: Wei, Peng;Tang, Hongwei;Li, Donghui
• 通讯作者: Li, Donghui

Body mass index and obesity- and diabetes-associated genotypes and risk for pancreatic cancer.

• DOI: 10.1158/1055-9965.epi-10-0845
• 发表时间: 2011-05
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: Tang H;Dong X;Hassan M;Abbruzzese JL;Li D
• 通讯作者: Li D

Powerful Tukey's One Degree-of-Freedom Test for Detecting Gene-Gene and Gene-Environment Interactions.

• DOI: 10.4137/cin.s17305
• 发表时间: 2015
• 期刊: Cancer informatics
• 影响因子: 2
• 作者: Wang Y;Li D;Wei P
• 通讯作者: Wei P

Insights into pancreatic cancer etiology from pathway analysis of genome-wide association study data.

• DOI: 10.1371/journal.pone.0046887
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Wei P;Tang H;Li D
• 通讯作者: Li D

Dietary N-Nitroso Compounds and Risk of Hepatocellular Carcinoma: A USA-Based Study.

• DOI: 10.1002/hep.32046
• 发表时间: 2021-12
• 期刊: Hepatology (Baltimore, Md.)
• 作者: Zheng J;Daniel CR;Hatia RI;Stuff J;Abdelhakeem AA;Rashid A;Chun YS;Jalal PK;Kaseb AO;Li D;Hassan MM
• 通讯作者: Hassan MM