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Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and CCR5, and risk of pancreatic adenocarcinoma.

Abstract

Adenocarcinoma of the exocrine pancreas is the fourth leading cause of cancer-related death in men and women in the U.S. Cytokines and other proinflammatory mediators have been implicated in inflammatory pancreatic diseases including pancreatitis and cancer. We analyzed cytokine gene polymorphisms as risk factors for pancreatic cancer using questionnaire data obtained by in-person interviews and germ line DNA collected in a population-based case-control study of pancreatic cancer (532 cases and 1,701 controls) conducted in the San Francisco Bay Area. We used mass spectrometry and gel-based methods to genotype 308 cases and 964 population-based controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression analysis and included adjustment for age, sex, and smoking. We assessed potential interactions between these polymorphisms, proinflammatory conditions (e.g., pancreatitis, ulcer, and obesity), and smoking as risk factors for pancreatic cancer. There was no overall association between pancreatic cancer risk and tumor necrosis factor-alpha (TNF-A -308G/A), regulated upon activation, normally T cell-expressed, and presumably secreted (RANTES -403G/A), and CC chemokine receptor 5 (CCR5-Delta32) polymorphisms. There was a nearly 7-fold increased relative risk estimate for pancreatic cancer in individuals with a history of pancreatitis (adjusted OR, 6.9; 95% CI, 3.4-14.1). Among patients with pancreatic cancer, pancreatitis was significantly associated with TNF-A -308 GA + AA (OR, 3.1; 95% CI, 1.3-7.4) and with RANTES -403 GA + AA (OR, 2.3; 95% CI, 1.0-5.4). There was evidence for a possible interaction between current active smoking and CCR5-32del. Our results lend support for the hypothesis that proinflammatory gene polymorphisms, in combination with proinflammatory conditions, may influence the development of pancreatic cancer.

Authors+Show Affiliations

Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH 03756, USA. Eric.Duell@Dartmouth.EduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16614115

Citation

Duell, Eric J., et al. "Inflammation, Genetic Polymorphisms in Proinflammatory Genes TNF-A, RANTES, and CCR5, and Risk of Pancreatic Adenocarcinoma." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 15, no. 4, 2006, pp. 726-31.
Duell EJ, Casella DP, Burk RD, et al. Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and CCR5, and risk of pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2006;15(4):726-31.
Duell, E. J., Casella, D. P., Burk, R. D., Kelsey, K. T., & Holly, E. A. (2006). Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and CCR5, and risk of pancreatic adenocarcinoma. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 15(4), pp. 726-31.
Duell EJ, et al. Inflammation, Genetic Polymorphisms in Proinflammatory Genes TNF-A, RANTES, and CCR5, and Risk of Pancreatic Adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2006;15(4):726-31. PubMed PMID: 16614115.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and CCR5, and risk of pancreatic adenocarcinoma. AU - Duell,Eric J, AU - Casella,Daniel P, AU - Burk,Robert D, AU - Kelsey,Karl T, AU - Holly,Elizabeth A, PY - 2006/4/15/pubmed PY - 2006/11/14/medline PY - 2006/4/15/entrez SP - 726 EP - 31 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol. Biomarkers Prev. VL - 15 IS - 4 N2 - Adenocarcinoma of the exocrine pancreas is the fourth leading cause of cancer-related death in men and women in the U.S. Cytokines and other proinflammatory mediators have been implicated in inflammatory pancreatic diseases including pancreatitis and cancer. We analyzed cytokine gene polymorphisms as risk factors for pancreatic cancer using questionnaire data obtained by in-person interviews and germ line DNA collected in a population-based case-control study of pancreatic cancer (532 cases and 1,701 controls) conducted in the San Francisco Bay Area. We used mass spectrometry and gel-based methods to genotype 308 cases and 964 population-based controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression analysis and included adjustment for age, sex, and smoking. We assessed potential interactions between these polymorphisms, proinflammatory conditions (e.g., pancreatitis, ulcer, and obesity), and smoking as risk factors for pancreatic cancer. There was no overall association between pancreatic cancer risk and tumor necrosis factor-alpha (TNF-A -308G/A), regulated upon activation, normally T cell-expressed, and presumably secreted (RANTES -403G/A), and CC chemokine receptor 5 (CCR5-Delta32) polymorphisms. There was a nearly 7-fold increased relative risk estimate for pancreatic cancer in individuals with a history of pancreatitis (adjusted OR, 6.9; 95% CI, 3.4-14.1). Among patients with pancreatic cancer, pancreatitis was significantly associated with TNF-A -308 GA + AA (OR, 3.1; 95% CI, 1.3-7.4) and with RANTES -403 GA + AA (OR, 2.3; 95% CI, 1.0-5.4). There was evidence for a possible interaction between current active smoking and CCR5-32del. Our results lend support for the hypothesis that proinflammatory gene polymorphisms, in combination with proinflammatory conditions, may influence the development of pancreatic cancer. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/16614115/Inflammation_genetic_polymorphisms_in_proinflammatory_genes_TNF_A_RANTES_and_CCR5_and_risk_of_pancreatic_adenocarcinoma_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16614115 DB - PRIME DP - Unbound Medicine ER -