title: No association between germline variation in catechol-O-methyltransferase and colorectal cancer survival in postmenopausal women.
abstract: OBJECTIVE
  Sex steroid hormones play a role in colorectal cancer (CRC) development, but little is known about their influence on tumor progression and metastasis. Because catechol-O-methyltransferase (COMT; 22q11.21) activity is an important component of estrogen-mediated carcinogenesis, we hypothesized that germline variation in COMT may be associated with CRC survival.
  
  
  METHODS
  We identified 10 single nucleotide polymorphisms that tagged variation across two isoforms of COMT in 2,458 women with CRC from the Nurses' Health Study, Postmenopausal Hormones Supplementary Study to the Colon Cancer Family Registry, VITamins And Lifestyle Study, and Women's Health Initiative. All four studies participated in the Genetics and Epidemiology of Colorectal Cancer Consortium.
  
  
  RESULTS
  During a median follow-up of 7 years across all studies, there were 799 deaths, including 566 deaths from CRC. Based on multiple comparisons, no associations between single nucleotide polymorphisms and CRC-specific or overall survival reached statistical significance, including the well-characterized Val108/158Met polymorphism (rs4680; CRC-specific survival: hazard ratio per minor allele, 1.04; 95% CI, 0.92-1.17; overall survival: hazard ratio per minor allele, 1.01; 95% CI, 0.90-1.14).
  
  
  CONCLUSIONS
  In this large study of women with CRC, we find no evidence that common inherited variation in COMT is associated with survival time after diagnosis.
authors.affiliation: From the 1Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 2Department of Epidemiology, University of Washington School of Public Health, Seattle, WA; 3Division of General Medical Disciplines, Stanford University School of Medicine, Stanford, CA; 4SRI International, Menlo Park, CA; 5Department of Biostatistics, University of Washington School of Public Health, Seattle, WA; 6Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ; 7Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and 8Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Passarelli
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.forename: Karen W
authors.initials: KW
authors.lastname: Makar
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Burnett-Hartman
authors.forename: Amanda I
authors.initials: AI
authors.lastname: Phipps
authors.forename: Sean P
authors.initials: SP
authors.lastname: David
authors.forename: Li
authors.initials: L
authors.lastname: Hsu
authors.forename: Tabitha A
authors.initials: TA
authors.lastname: Harrison
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Hutter
authors.forename: David J
authors.initials: DJ
authors.lastname: Duggan
authors.forename: Emily
authors.initials: E
authors.lastname: White
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
mesh_terms: D000368:Aged; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality*; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017698:Postmenopause; D015996:Survival Rate; D016387:Women's Health
chemical_list: D002394:Catechol O-Methyltransferase