Cancer Causes & Control

, Volume 22, Issue 7, pp 955–963 | Cite as

Variation in the CYP19A1 gene and risk of colon and rectal cancer

  • Martha L. Slattery
  • Abbie Lundgreen
  • Jennifer S. Herrick
  • Susan Kadlubar
  • Bette J. Caan
  • John D. Potter
  • Roger K. Wolff
Original paper

Abstract

CYP19A1, or aromatase, influences estrogen-metabolizing enzymes and may influence cancer risk. We examine variation in the CYP19A1 gene and risk of colorectal cancer using data from population-based case–control studies (colon n = 1,574 cases, 1,970 controls; rectal n = 791 cases, 999 controls). Four SNPs were statistically significantly associated with colon cancer and four were associated with rectal cancer. After adjustment for multiple comparisons, the AA genotype of rs12591359 was associated with an increased risk of colon cancer (OR 1.44 95% CI 1.16–1.80) and the AA genotype of rs2470144 was associated with a reduced risk of rectal cancer (OR 0.65 95% CI 0.50–0.84). Variants of CYP19A1 were associated with CIMP+ and CIMP+/KRAS2-mutated tumors. CT/TT genotypes of rs1961177 were significantly associated with an increased likelihood of a MSI+ colon tumor (OR 1.77 95% CI 1.26–2.37). We observed statistically significant interactions between genetic variation in NFκB1 and CYP19A1 for both colon and rectal cancer. Our data suggest the importance of CYP19A1 in the development of colon and rectal cancer and that estrogen may influence risk through an inflammation-related mechanism.

Keywords

Colon cancer Rectal cancer CYP19A1 NFκB1 Aspirin BMI CIMP+ KRAS2 MSI 

Supplementary material

10552_2011_9768_MOESM1_ESM.doc (116 kb)
Supplementary material 1 (DOC 70 kb)

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Martha L. Slattery
    • 1
  • Abbie Lundgreen
    • 1
  • Jennifer S. Herrick
    • 1
  • Susan Kadlubar
    • 2
  • Bette J. Caan
    • 3
  • John D. Potter
    • 4
  • Roger K. Wolff
    • 1
  1. 1.Department of Internal MedicineUniversity of Utah Health Sciences CenterSalt Lake CityUSA
  2. 2.University of ArkansasLittle RockUSA
  3. 3.Division of ResearchKaiser Permanente Medical Research ProgramOaklandUSA
  4. 4.Fred Hutchinson Cancer Research CenterSeattleUSA

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