Iron Status and Cancer Risk in UK Biobank: A Two-Sample Mendelian Randomization Study

Abstract

We conducted a two-sample Mendelian randomization study to explore the associations of iron status with overall cancer and 22 site-specific cancers. Single-nucleotide polymorphisms for iron status were obtained from a genome-wide association study of 48,972 European-descent individuals. Summary-level data for breast and other cancers were obtained from the Breast Cancer Association Consortium and UK Biobank. Genetically predicted iron status was positively associated with liver cancer and inversely associated with brain cancer but not associated with overall cancer or the other 20 studied cancer sites at p < 0.05. The odds ratios of liver cancer were 2.45 (95% CI, 0.81, 7.45; p = 0.11), 2.11 (1.16, 3.83; p = 0.02), 10.89 (2.44, 48.59; p = 0.002) and 0.30 (0.17, 0.53; p = 2 × 10−5) for one standard deviation increment of serum iron, transferrin saturation, ferritin and transferrin levels, respectively. For brain cancer, the corresponding odds ratios were 0.69 (0.48, 1.00; p = 0.05), 0.75 (0.59, 0.97; p = 0.03), 0.41 (0.20, 0.88; p = 0.02) and 1.49 (1.04, 2.14; p = 0.03). Genetically high iron status was positively associated with liver cancer and inversely associated with brain cancer.

Association between serum iron status and primary liver cancer risk: a Mendelian randomization analysis

“…The causal relationship between iron status and PLC development is debatable and needs further investigations. In a recent 2-sample MR analysis, Yuan et al reported that genetically predicted iron status was positively associated with liver cancer (21). However, only 3 SNPs were used to serve as genetic instruments of iron status in this study, and thus may have led to a weak instrumental variable bias.…”

Urban–rural disparity in cancer incidence in China, 2008–2012: a cross-sectional analysis of data from 36 cancer registers

“… 5 6 Our findings were in line with these reports, which stressed the need for targeted prevention strategies for these cancers in rural areas. As many modifiable factors, including obesity, 17 nutrition, 18 Helicobacter pylori infection, 19 virus infection, 20 alcohol use 21 and smoking 20 are important risk factors for stomach and/or liver cancers, primary prevention strategy targeting at these dimensions may be implemented in rural areas to narrow the urban–rural disparity in these cancers.…”

Distribution and associated factors of hepatic iron – a population-based imaging study

“…Genetic variants rs1799945 and rs1800562 in HFE showed the strongest association with HIC in men and women, respectively. Both SNPs lead to hepatic iron overload due to decreased hepcidin levels (30,31) and are additionally associated with ferritin and transferrin (32,33). Moreover, variants rs855791 and rs4820268 in TMPRSS6 are known to be associated with iron traits including transferrin, serum iron and ferritin (34,30), since TMPRSS6 modulates the transcription of hepcidin (34).…”