Iron, Copper, and Magnesium Concentration in Hair and Risk of Esophageal Cancer: A Nested Case-Control Study

Background: An association has already been hypothesized between iron, copper, and magnesium status assessed through food frequency questionnaires (FFQs) and the risk of esophageal squamous cell carcinoma (ESCC). However, self -reported dietary assessment methods are prone to measurement errors. We studied the association between iron, copper, and magnesium status and ESCC risk, using hair samples as a long exposure biomarker. Methods: We designed a nested case -control study within the Golestan Cohort Study, that recruited about 50 000 participants in 2004-2008, and collected biospecimens at baseline. We identified 96 incident cases of ESCC with available hair samples. They were age -matched with cancer -free controls from the cohort. We used inductively coupled plasma mass spectrometry (ICP-MS) to measure iron, copper, and magnesium concentrations in hair samples. We used multiple logistic regression models to determine odds ratios and 95% confidence intervals. Results: Median concentrations of iron, copper, and magnesium were 35.4, 19.3, and 41.7 ppm in cases and 25.8, 18.3, and 50.0 ppm in controls, respectively. Iron was significantly associated with the risk of ESCC in continuous analysis (OR = 1.41, 95% CI = 1.03-1.92), but not in the tertiles analyses (ORT3 vs. T1 = 1.81, 95% CI = 0.77-4.28). No associations were observed between copper and magnesium and ESCC risk, in either the tertiles models or the continuous estimate (copper: ORT3 vs. T1=2.56, 95% CI =1.00-6.54; magnesium: ORT3 vs. T1= 0.75, 95% CI = 0.32-1.78). Conclusion: Higher iron status may be related to a higher risk of ESCC in this population.