Iron homeostasis and distal colorectal adenoma risk in the prostate, lung, colorectal, and ovarian cancer screening trial

Amanda J. Cross, Rashmi Sinha, Richard J. Wood, Xiaonan (Nan) Xue, Wen Yi Huang, Meredith Yeager, Richard B. Hayes, Marc J. Gunter

Research output: Contribution to journalArticle

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Abstract

Red meat consumption has been positively associated with colorectal cancer; however, the biological mechanism underlying this relationship is not understood. Red meat is a major source of iron, which may play a role in colorectal carcinogenesis via increased crypt cell proliferation, cytotoxicity, and endogenous N-nitrosation. In a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we prospectively evaluated multiple iron exposure parameters, including dietary intake and serum measures of iron, ferritin, transferrin, total iron binding capacity (TIBC), and unsaturated iron binding capacity (UIBC) in relation to incident colorectal adenoma in 356 cases and 396 matched polypfree controls. We also investigated variation in eight key genes involved in iron homeostasis in relation to colorectal adenoma in an additional series totaling 1,126 cases and 1,173 matched controls. We observed a positive association between red meat intake and colorectal adenoma [OR comparing extreme quartiles (OR q4-q1) = 1.59, 95% CI = 1.02-2.49, P trend = 0.03]. Serum TIBC and UIBC were inversely associated with colorectal adenoma (OR q4-q1 = 0.57, 95% CI = 0.37-0.88, P trend = 0.03; and OR q4-q1 = 0.62, 95% CI = 0.40-0.95, P trend = 0.04, respectively). Colorectal adenoma was not associated with serum ferritin, iron, or transferrin saturation or with polymorphisms in genes involved in iron homeostasis. Serum TIBC and UIBC, parameters that have a reciprocal relationship with overall iron load, were inversely related to colorectal adenoma, suggesting that individuals with lower iron status have a reduced risk of developing colorectal adenoma.

Original languageEnglish (US)
Pages (from-to)1465-1475
Number of pages11
JournalCancer Prevention Research
Volume4
Issue number9
DOIs
StatePublished - Sep 2011

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Early Detection of Cancer
Adenoma
Ovarian Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Prostatic Neoplasms
Homeostasis
Iron
Transferrin
Ferritins
Serum
Nitrosation
Genes
Case-Control Studies
Carcinogenesis
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Iron homeostasis and distal colorectal adenoma risk in the prostate, lung, colorectal, and ovarian cancer screening trial. / Cross, Amanda J.; Sinha, Rashmi; Wood, Richard J.; Xue, Xiaonan (Nan); Huang, Wen Yi; Yeager, Meredith; Hayes, Richard B.; Gunter, Marc J.

In: Cancer Prevention Research, Vol. 4, No. 9, 09.2011, p. 1465-1475.

Research output: Contribution to journalArticle

Cross, Amanda J. ; Sinha, Rashmi ; Wood, Richard J. ; Xue, Xiaonan (Nan) ; Huang, Wen Yi ; Yeager, Meredith ; Hayes, Richard B. ; Gunter, Marc J. / Iron homeostasis and distal colorectal adenoma risk in the prostate, lung, colorectal, and ovarian cancer screening trial. In: Cancer Prevention Research. 2011 ; Vol. 4, No. 9. pp. 1465-1475.
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