title: Aryl hydrocarbon receptor expression is associated with a family history of upper gastrointestinal tract cancer in a high-risk population exposed to aromatic hydrocarbons.
abstract: BACKGROUND
  Polycyclic aromatic hydrocarbon (PAH) exposure is a risk factor for esophageal squamous cell carcinoma, and PAHs are ligands of the aryl hydrocarbon receptor (AhR). This study measured the expression of AhR and related genes in frozen esophageal cell samples from patients exposed to different levels of indoor air pollution, who did or did not have high-grade squamous dysplasia and who did or did not have a family history of upper gastrointestinal tract (UGI) cancer.
  
  
  METHODS
  147 samples were evaluated, including 23 (16%) from patients with high-grade dysplasia and 48 (33%) from patients without dysplasia who heated their homes with coal, without a chimney (a "high" indoor air pollution group), and 27 (18%) from patients with high-grade dysplasia and 49 (33%) from patients without dysplasia who did not heat their homes at all (a "low" indoor air pollution group). Sixty-four (44%) had a family history of UGI cancer. RNA was extracted and quantitative PCR analysis was done.
  
  
  RESULTS
  AhR gene expression was detectable in 85 (58%) of the samples and was >9-fold higher in those with a family history of UGI cancer [median expression (interquartile range), -1,964 (-18,000, -610) versus -18,000 (-18,000, -1036); P = 0.02, Wilcoxon rank-sum test]. Heating status, dysplasia category, age, gender, and smoking were not associated with AhR expression (linear regression; all P values >or= 0.1).
  
  
  CONCLUSIONS
  AhR expression was higher in patients with a family history of UGI cancer. Such individuals may be more susceptible to the deleterious effects of PAH exposure, including PAH-induced cancer.
authors.affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7232, USA. mr166i@nih.gov
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Roth
authors.forename: Wen-Qiang
authors.initials: WQ
authors.lastname: Wei
authors.forename: Jessica
authors.initials: J
authors.lastname: Baer
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Wang
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Sternberg
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Warner
authors.forename: Laura Lee
authors.initials: LL
authors.lastname: Johnson
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.forename: Carol A
authors.initials: CA
authors.lastname: Giffen
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Dawsey
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Qiao
authors.forename: James
authors.initials: J
authors.lastname: Cherry
mesh_terms: D000368:Aged; D016902:Air Pollution, Indoor / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*; D003430:Cross-Sectional Studies; D004938:Esophageal Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D011084:Polycyclic Aromatic Hydrocarbons / Q000506:poisoning*; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis* / Q000235:genetics; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon
references.citation: Carcinogenesis. 2004 Nov;25(11):2275-81
references.pmid: 15297370
references.citation: Chem Res Toxicol. 2003 Mar;16(3):249-60
references.pmid: 12641424
references.citation: Carcinogenesis. 2002 Apr;23(4):611-6
references.pmid: 11960914
references.citation: J Biol Chem. 2001 Aug 31;276(35):33101-10
references.pmid: 11423533
references.citation: Gut. 2005 Feb;54(2):187-92
references.pmid: 15647178
references.citation: Genes Dev. 1999 Jan 1;13(1):20-5
references.pmid: 9887096
references.citation: Toxicol In Vitro. 2006 Jun;20(4):426-38
references.pmid: 16198082
references.citation: Hum Pathol. 1998 Nov;29(11):1294-8
references.pmid: 9824110
references.citation: Int J Cancer. 2005 Jan 20;113(3):456-63
references.pmid: 15455378
references.citation: Cancer Causes Control. 2008 Feb;19(1):1-12
references.pmid: 17906935
references.citation: Carcinogenesis. 1999 Feb;20(2):243-8
references.pmid: 10069460
references.citation: Int J Cancer. 2003 Jan 1;103(1):5-11
references.pmid: 12455047
references.citation: Nat Rev Cancer. 2006 Dec;6(12):947-60
references.pmid: 17128211
references.citation: Int J Epidemiol. 1992 Oct;21(5):877-82
references.pmid: 1468848
references.citation: Curr Drug Metab. 2001 Jun;2(2):149-64
references.pmid: 11469723
references.citation: Biochem Pharmacol. 2000 Jan 1;59(1):65-85
references.pmid: 10605936
references.citation: Fam Cancer. 2008;7(1):27-39
references.pmid: 17999161
references.citation: Semin Cancer Biol. 2004 Dec;14(6):473-86
references.pmid: 15489140
references.citation: Annu Rev Pharmacol Toxicol. 1995;35:307-40
references.pmid: 7598497
references.citation: Cancer Causes Control. 1992 Mar;3(2):107-13
references.pmid: 1562700
references.citation: Biomarkers. 2001;6(5):381-6
references.pmid: 23889311
references.citation: Cancer. 1994 Apr 15;73(8):2027-37
references.pmid: 8156507
references.citation: Cancer Epidemiol Biomarkers Prev. 2000 Jan;9(1):3-28
references.pmid: 10667460
references.citation: Lancet Oncol. 2005 Dec;6(12):931-2
references.pmid: 16353404
references.citation: World J Gastroenterol. 2004 Apr 1;10(7):940-4
references.pmid: 15052670
references.citation: Clin Cancer Res. 2007 Jan 1;13(1):38-45
references.pmid: 17200336
references.citation: Eur J Cancer. 1998 Apr;34(5):757-8
references.pmid: 9713287
references.citation: Int J Cancer. 2002 Nov 20;102(3):271-4
references.pmid: 12397650
references.citation: Mol Aspects Med. 1999 Feb-Apr;20(1-2):55-70, 137
references.pmid: 10575652
references.citation: Biochem Pharmacol. 1999 Jul 1;58(1):157-65
references.pmid: 10403529
references.citation: Clin Med (Lond). 2005 Sep-Oct;5(5):491-8
references.pmid: 16268333
references.citation: Arch Biochem Biophys. 2007 Aug 15;464(2):207-12
references.pmid: 17481570
references.citation: Gut. 2005 Jun;54(6):759-63
references.pmid: 15888779
references.citation: BMC Cancer. 2006 May 26;6:139
references.pmid: 16729889
references.citation: J Biochem Mol Toxicol. 2005;19(6):368-78
references.pmid: 16421897
references.citation: Mol Aspects Med. 2006 Apr-Jun;27(2-3):126-39
references.pmid: 16469371
references.citation: Toxicol Appl Pharmacol. 2004 Sep 15;199(3):210-9
references.pmid: 15364538
references.citation: Anticancer Res. 2005 Jan-Feb;25(1B):425-8
references.pmid: 15816606
references.citation: Genes Chromosomes Cancer. 2001 Aug;31(4):390-7
references.pmid: 11433530
references.citation: Acta Cytol. 2008 Jan-Feb;52(1):14-23
references.pmid: 18323271
references.citation: Cancer. 1997 Sep 1;80(5):852-7
references.pmid: 9307183
references.citation: Toxicol Lett. 2006 Aug 20;165(2):182-94
references.pmid: 16713138
references.citation: Cancer Prev Res (Phila). 2008 Jul;1(2):100-11
references.pmid: 19138943
references.citation: Genes Chromosomes Cancer. 2005 Nov;44(3):271-8
references.pmid: 16015646