title: Associations between Environmental Exposures and Incident Colorectal Cancer by ESR2 Protein Expression Level in a Population-Based Cohort of Older Women.
abstract: BACKGROUND
  Cigarette smoking (smoking), hormone therapy (MHT), and folate intake (folate) are each thought to influence colorectal cancer risk, but the underlying molecular mechanisms remain incompletely defined. Expression of estrogen receptor β (ESR2) has been associated with colorectal cancer stage and survival.
  
  
  METHODS
  In this prospective cohort study, we examined smoking, MHT, and folate-associated colorectal cancer risks by ESR2 protein expression level among participants in the Iowa Women's Health Study (IWHS). Self-reported exposure variables were assessed at baseline. Archived, paraffin-embedded colorectal cancer tissue specimens were collected and evaluated for ESR2 protein expression by IHC. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI) for associations between smoking, MHT, or folate and ESR2-defined colorectal cancer subtypes.
  
  
  RESULTS
  Informative environmental exposure and protein expression data were available for 491 incident colorectal cancer cases. Positive associations between ESR2-low and -high tumors and several smoking-related variables were noted, most prominently with average number of cigarettes per day (RR, 4.24; 95% CI, 1.81-9.91 for ESR2-low and RR, 2.15; 95% CI, 1.05-4.41 for ESR2-high for ≥40 cigarettes compared with nonsmokers). For MHT, a statistically significant association with ESR2-low tumors was observed with longer duration of exposure (RR, 0.54; 95% CI, 0.26-1.13 for >5 years compared with never use). No associations were found for folate.
  
  
  CONCLUSIONS
  In this study, smoking and MHT were associated with ESR2 expression patterns.
  
  
  CONCLUSIONS
  These data support possible heterogeneous effects from smoking and MHT on ERβ-related pathways of colorectal carcinogenesis in older women.
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors: Lori S
authors: LS
authors: Tillmans
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors: Robert A
authors: RA
authors: Vierkant
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors: Alice H
authors: AH
authors: Wang
authors: Department of Medicine (Gastroenterology), Huntsman Cancer Institute and University of Utah, Salt Lake City, Utah.
authors: Niloy Jewel
authors: NJ
authors: Samadder
authors: Department of Epidemiology, University of Iowa, Iowa City, Iowa.
authors: Charles F
authors: CF
authors: Lynch
authors: Department of Epidemiology, University of Minnesota, Minneapolis, Minnesota.
authors: Kristin E
authors: KE
authors: Anderson
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors: Amy J
authors: AJ
authors: French
authors: Stanford Cancer Institute, Palo Alto, California.
authors: Robert W
authors: RW
authors: Haile
authors: Department of Epidemiology, University of Minnesota, Minneapolis, Minnesota.
authors: Lisa J
authors: LJ
authors: Harnack
authors: Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: John D
authors: JD
authors: Potter
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors: Susan L
authors: SL
authors: Slager
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors: Thomas C
authors: TC
authors: Smyrk
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors: Stephen N
authors: SN
authors: Thibodeau
authors: Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
authors: James R
authors: JR
authors: Cerhan
authors: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. limburg.paul@mayo.edu.
authors: Paul J
authors: PJ
authors: Limburg
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000378:metabolism; D004781:Environmental Exposure; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D011795:Surveys and Questionnaires
chemical_list: C000600034:ESR2 protein, human; D047629:Estrogen Receptor beta
references: J Natl Cancer Inst. 2006 Dec 6;98(23):1731-8
references: 17148775
references: Br J Cancer. 2012 Aug 21;107(5):831-9
references: 22828608
references: J Clin Oncol. 1999 May;17(5):1474-81
references: 10334533
references: World J Gastroenterol. 2004 Jan 15;10(2):214-7
references: 14716825
references: Cancer Res. 2013 Jun 1;73(11):3306-15
references: 23585455
references: Cancer Epidemiol Biomarkers Prev. 2012 Apr;21(4):681-4
references: 22337533
references: Eur J Cancer. 2003 Jun;39(9):1251-8
references: 12763213
references: Gut. 2011 Mar;60(3):397-411
references: 21036793
references: Hum Pathol. 2001 Sep;32(9):940-4
references: 11567223
references: Biometrics. 1995 Jun;51(2):524-32
references: 7662841
references: N Engl J Med. 2004 Mar 4;350(10):991-1004
references: 14999111
references: Lancet Oncol. 2008 Apr;9(4):385-91
references: 18374292
references: Am J Epidemiol. 2013 Apr 1;177(7):625-37
references: 23459948
references: Histopathology. 2007 Jan;50(1):113-30
references: 17204026
references: Aliment Pharmacol Ther. 2010 Apr;31(7):708-18
references: 20085565
references: Cancer. 2001 Nov 15;92(10):2547-54
references: 11745188
references: Steroids. 2008 Oct;73(9-10):853-8
references: 18206197
references: Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):1012-8
references: 12376501
references: J Natl Cancer Inst. 2010 Jul 21;102(14):1012-22
references: 20587792
references: J Pathol. 2002 Jun;197(2):155-62
references: 12015738
references: Gastroenterology. 2010 Jun;138(6):2088-100
references: 20420948
references: Cancer Causes Control. 2003 Dec;14(10):979-84
references: 14750537
references: Am J Epidemiol. 1997 Jan 1;145(1):72-80
references: 8982025
references: Cancer. 1999 Apr 15;85(8):1670-6
references: 10223559
references: Cancer Epidemiol Biomarkers Prev. 2014 Feb;23(2):350-5
references: 24343843
references: Patholog Res Int. 2012;2012:597497
references: 22997602
references: JAMA. 2008 Dec 17;300(23):2765-78
references: 19088354
references: World J Gastroenterol. 2013 Jul 21;19(27):4325-33
references: 23885143
references: Am J Epidemiol. 1990 May;131(5):794-803
references: 2138863
references: Am J Epidemiol. 1988 Jan;127(1):188-99
references: 3337073
references: Biochem Biophys Res Commun. 2007 Jul 20;359(1):102-7
references: 17524358
references: Cancer Epidemiol Biomarkers Prev. 1999 Dec;8(12):1117-21
references: 10613347
references: J Natl Cancer Inst. 2000 Nov 15;92(22):1831-6
references: 11078760
references: Am J Epidemiol. 2010 Nov 1;172(9):1000-14
references: 20937634
references: Gut. 2012 Sep;61(9):1299-305
references: 22027477
references: Cancer Prev Res (Phila). 2011 Nov;4(11):1808-15
references: 21680706
references: CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29
references: 24399786
references: J Mol Diagn. 2008 Jan;10(1):13-27
references: 18165277
references: Carcinogenesis. 2013 Apr;34(4):909-15
references: 23276798
references: Cancer Causes Control. 1999 Oct;10(5):467-73
references: 10530618
references: Am J Gastroenterol. 2012 May;107(5):782-9
references: 22349355
references: J Cell Physiol. 2005 Apr;203(1):193-201
references: 15389627
references: Nutr Cancer. 2012;64(7):899-910
references: 23061900
references: PLoS One. 2011;6(6):e21102
references: 21738611
references: Cancer Causes Control. 2010 Nov;21(11):1919-30
references: 20820900
references: Br J Nutr. 2007 Dec;98(6):1299-304
references: 17764601
references: J Natl Cancer Inst. 1980 Dec;65(6):1201-7
references: 7001123