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

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 polyp-free 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.

• Authors: Amanda J Cross, Rashmi Sinha, Richard J Wood, Xiaonan Xue, Wen-Yi Huang, Meredith Yeager, Richard B Hayes, Marc J Gunter
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 4 Issue 9 Pg. 1465-75 (Sep 2011) ISSN: 1940-6215 [Electronic] United States
• PMID: 21685236 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Intramural)
• Copyright: ©2011 AACR.

Chemical References

• Iron

Topics

• Adenoma (metabolism)
• Aged
• Colorectal Neoplasms (diagnosis, metabolism)
• Female
• Genotype
• Homeostasis
• Humans
• Iron (chemistry, metabolism)
• Lung Neoplasms (metabolism)
• Male
• Mass Screening (methods)
• Meat
• Medical Oncology (methods)
• Middle Aged
• Ovarian Neoplasms (metabolism)
• Polymorphism, Single Nucleotide
• Prostatic Neoplasms (metabolism)
• Sigmoidoscopy (methods)