High Serum Iron Is Associated with Increased Cancer Risk

Chi Pang Wen, June Han Lee, Ya-Ping Tai, Christopher Wen, Shiuan Be Wu, Min Kuang Tsai, Dennis P H Hsieh, Hung-Che Chiang, Chao Agnes Hsiung, Chung Y Hsu, Xifeng Wu

Epidemiological studies linking high serum iron with cancer risks are limited and inconclusive, despite evidence implicating body iron in human carcinogenesis. A cohort of 309,443 adults in Taiwan who had no history of cancer had serum iron levels tested at the time of recruitment (1997 - 2008). Initially measured iron levels were associated with subsequent cancer risk by linking individuals with the National Cancer Registry and National Death File. Hazard ratios were calculated by the Cox model. One-third of males (35%) and one-fifth of females (18%) had high serum iron (≧120 μg/dL), which was associated with a 25% increase in risk for incidence of all cancers (Hazard Ratio (HR): 1.25, 95% confidence interval (CI): 1.16-1.35) and with a 39% increase in risk for mortality from all cancers (HR: 1.39, 95% CI: 1.23-1.57). The relationship between serum iron and cancer risk was a J-shaped one, with higher cancer risk at both ends, either at lower than 60 μg/dL or higher than 120 μg/dL. At higher end, cancer risk increased by 4% for every 10 μg/dL increment above 80 μg/dL, showing a dose response relationship, with 60-79 μg/dL as a reference level. In a sensitivity analysis, the increases in risk were still observed after the first five years of cancer cases were excluded. Liver cancer risk was increased in HBV (-) subjects (3-fold) and HBV (+) subjects (24-fold). Lifestyle risks such as smoking, drinking or inactivity interacted synergistically with high serum iron and significantly increased the cancer risks. The risk remained elevated after first 5 years of observation. The liver (HR: 2.98, 95% CI: 2.32-3.84) and the breast (HR: 1.31, 95% CI: 1.01-1.70) were the two major cancer sites where significant cancer risks were observed for serum iron ≧140 μg/dL. This study reveals that high serum iron is both a common disorder and a marker of increased risk for several cancers.