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

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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.

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Acknowledgments

This study was funded by NCI Grants CA48998 and CA61757. This research also was supported by the Utah Cancer Registry, which is funded by Contract #N01-PC-67000 from the National Cancer Institute, with additional support from the State of Utah Department of Health, the Northern California Cancer Registry, and the Sacramento Tumor Registry. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute. We would like to acknowledge the contributions of Sandra Edwards, Roger Edwards, Leslie Palmer, Donna Schaffer, Dr. Kristin Anderson, and Judy Morse for data management and collection.

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No authors have any conflict of interest to report.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Utah Health Sciences Center, 295 Chipeta Way, Salt Lake City, UT, 84108, USA

    Martha L. Slattery, Abbie Lundgreen, Jennifer S. Herrick & Roger K. Wolff

  2. University of Arkansas, Little Rock, AR, USA

    Susan Kadlubar

  3. Division of Research, Kaiser Permanente Medical Research Program, Oakland, CA, USA

    Bette J. Caan

  4. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    John D. Potter

Authors
  1. Martha L. Slattery
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  2. Abbie Lundgreen
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  3. Jennifer S. Herrick
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  4. Susan Kadlubar
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  5. Bette J. Caan
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  7. Roger K. Wolff
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Correspondence to Martha L. Slattery.

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Slattery, M.L., Lundgreen, A., Herrick, J.S. et al. Variation in the CYP19A1 gene and risk of colon and rectal cancer. Cancer Causes Control 22, 955–963 (2011). https://doi.org/10.1007/s10552-011-9768-x

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  • DOI: https://doi.org/10.1007/s10552-011-9768-x

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