Postmenopausal hormone therapy and colorectal cancer risk in relation to somatic KRAS mutation status among older women

Paul John Limburg, David Limsui, Robert A. Vierkant, Lori S. Tillmans, Alice H. Wang, Charles F. Lynch, Kristin E. Anderson, Amy J. French, Robert W. Haile, Lisa J. Harnack, John D. Potter, Susan L Slager, Thomas Christopher Smyrk, Stephen N Thibodeau, James R Cerhan

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19 Scopus citations

Abstract

Background: Postmenopausal hormone (PMH) therapy represents a controversial colorectal cancer (CRC) preventive intervention. Because colorectal carcinogenesis is a heterogeneous process, we evaluated associations between PMH therapy and incident CRC in relation to KRAS mutation status in a population-based cohort of older women [Iowa Women's Health Study (IWHS)]. Methods: The IWHS enrolled 41,836 randomly selected women, ages 55 to 69 years, in 1986. PMH therapy and other exposure data were recorded at baseline. Tissue samples from prospectively identified CRC cases (n = 507) were analyzed for somatic KRAS mutations (exon 2, codons 12 and 13). Multivariable Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Results: PMH therapy (ever vs. never) was inversely associated with KRAS mutation-negative (RR = 0.83; 95% CI, 0.66-1.06; P = 0.14) and KRAS mutation-positive (RR = 0.82; 95% CI, 0.58-1.16; P = 0.27) tumors, although the observed risk estimates were not statistically significant. When anatomic subsite was additionally considered, the strongest association was found for KRAS mutation-negative, distal colorectal tumors (RR = 0.64; 95% CI, 0.43-0.96; P = 0.03). Conclusions: To our knowledge, we provide the first report of KRAS-defined CRC risks associated with PMHtherapy. These data suggest thatPMHtherapy may reduce CRC risk through mechanisms beyond KRAS mutation status but might provide greater benefits forKRASmutation-negative than mutation-positive tumors (at least in the distal colorectum). Impact: Findings from this prospective cohort study provide novel insights about the molecular biology of PMH therapy-related CRC risk reduction.

Original languageEnglish (US)
Pages (from-to)681-684
Number of pages4
JournalCancer Epidemiology Biomarkers and Prevention
Volume21
Issue number4
DOIs
StatePublished - Apr 2012

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ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Limburg, P. J., Limsui, D., Vierkant, R. A., Tillmans, L. S., Wang, A. H., Lynch, C. F., Anderson, K. E., French, A. J., Haile, R. W., Harnack, L. J., Potter, J. D., Slager, S. L., Smyrk, T. C., Thibodeau, S. N., & Cerhan, J. R. (2012). Postmenopausal hormone therapy and colorectal cancer risk in relation to somatic KRAS mutation status among older women. Cancer Epidemiology Biomarkers and Prevention, 21(4), 681-684. https://doi.org/10.1158/1055-9965.EPI-11-1168