Causal relationship between blood metal levels and breast cancer risk: a Mendelian randomization study in East Asian...

Studies in European populations have shown an association between blood metal levels and cancer risk. This study aimed to investigate the causal relationship between breast cancer (BC) risk and blood metal levels in East Asian populations using Mendelian randomization (MR).

The BC outcome data were obtained from the Biobank Japan database (2020), encompassing 95,283 East Asian women, including 5,552 cases of BC and 89,731 controls. BC was classified according to the ICD-10 code C509 (malignant neoplasm of the breast, unspecified). Exposure data regarding blood metal levels were obtained from a genome-wide association study (GWAS) involving the Chinese population conducted in 2022. In this study, the levels of 21 metals in serum and plasma were evaluated using inductively coupled plasma mass spectrometry (ICP-MS). MR analyses employed five methods: inverse variance weighted (IVW), contamination mixture (CM), mendelian randomization and robust adjusted profile score (MR-RAPS), debiased inverse variance weighted (dIVW), and constrained maximum likelihood and Model Average (cML-MA). Furthermore, we performed heterogeneity and horizontal pleiotropy assessments on the study results to evaluate their robustness.

Plasma lead levels were robustly and positively associated with BC risk. IVW model [OR = 1.154, 95%CI: 1.062-1.255, P = 0.001, P-FDR = 0.030]. No significant heterogeneity (Cochran's Q: P = 0.832), pleiotropy (MR-Egger intercept: P = 0.799) and reverse causality were found. Other blood metal levels (aluminum, arsenic, barium, calcium, cadmium, cobalt, chromium, copper, iron, magnesium, manganese, molybdenum, nickel, rubidium, selenium, tin, strontium, titanium, vanadium, zinc) were not significantly associated with BC (P > 0.05).

Elevated plasma lead levels are a significant risk factor for BC in East Asian populations, offering valuable insights into the prevention of BC.