Iron Consumption and Colorectal Cancer in Korean Adults: A Prospective Cohort Study

Abstract

Background/Objectives: Colorectal cancer (CRC) is a major health concern in Korea, with its increasing incidence emphasizing the urgent need to identify risk factors. Recent studies suggest that heme iron elevates CRC risk, but evidence remains conflicting. This study examined the associations between total, heme, and non-heme iron intake and the incidence of colorectal, colon, and rectal cancer in Koreans. Methods: Using the Korean Genome and Epidemiology Study Health Examinee (KoGES HEXA) cohort, a large community-based cohort of healthy Koreans, we constructed a database of iron content for foods listed in a validated food frequency questionnaire (FFQ) and assessed dietary iron intake for each participant. Colorectal, colon, and rectal cancer cases were identified via the national cancer registry up to 2018. The association between iron consumption and cancers was evaluated with hazard ratios (HRs) and 95% confidence intervals (95%CIs) using multivariable-adjusted Cox regression. Results: During the 9.1-year median follow-up of 109,908 participants (37,697 men and 71,401 women, median age: 53.8 years), 608 new CRC cases were identified. Moderate total iron consumption in the second quintile (5.00-6.27 mg/day) decreased CRC (HR: 0.75; 95%CI: 0.58-0.97) and colon cancer (HR: 0.71; 95%CI: 0.51-1.00) risk compared to the lowest consumption quintile (1.09-4.99 mg/day), as did non-heme iron intake in the second quintile (4.98-6.24 mg/day) compared to its lowest quintile (1.09-4.97 mg/day) (CRC HR: 0.75; 95%CI: 0.58-0.98; colon cancer HR: 0.70; 95%CI: 0.49-0.98). Conclusions: Moderate total and non-heme iron intake reduced colorectal and colon cancer risk in Koreans, possibly via the displacement of carcinogens and the increased intake of protective micronutrients from plant-based foods. Larger-scale studies may be instrumental in substantiating these results.

Keywords: colon cancer; colorectal cancer; diet; heme; iron; prospective studies; rectal cancer.

Figure 1

Flowchart for the overall selection process. In accordance with the Health Examinees-Gem (HEXA-G) participant eligibility criteria, participants under 40 years or over 69 years of age, as well as those recruited from sites that only participated in the pilot phase, participated for less than 2 years, or did not meet the biospecimen quality control criteria, were excluded (n = 139,267). Individuals missing mortality data or cancer registry data (n = 23,211), individuals with any prior history of cancer (n = 3771), those with follow-up periods of less than 2 years (n = 447), and those with missing dietary data (n = 1349) or reporting unreasonable total energy consumption values, defined as <800 or >4200 kcal/day for men and <500 or >3500 kcal/day for women, were also excluded (n = 1391).