TY - JOUR
T1 - Iron homeostasis and distal colorectal adenoma risk in the prostate, lung, colorectal, and ovarian cancer screening trial
AU - Cross, Amanda J.
AU - Sinha, Rashmi
AU - Wood, Richard J.
AU - Xue, Xiaonan
AU - Huang, Wen Yi
AU - Yeager, Meredith
AU - Hayes, Richard B.
AU - Gunter, Marc J.
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80052583592&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052583592&partnerID=8YFLogxK
U2 - 10.1158/1940-6207.CAPR-11-0103
DO - 10.1158/1940-6207.CAPR-11-0103
M3 - Article
C2 - 21685236
AN - SCOPUS:80052583592
SN - 1940-6207
VL - 4
SP - 1465
EP - 1475
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 9
ER -