A Metallomic Approach to Assess Associations of Serum Metal Levels With Gallstones and Gallbladder Cancer

Abstract

Background and aims: Exposure to metals may promote the risk for cancers. We evaluated the associations of a broad spectrum of metals with gallbladder cancer (GBC) and gallstones.

Approach and results: A total of 259 patients with GBC, 701 patients with gallstones, and 851 population-based controls were enrolled in Shanghai, China. A metallome panel was used to simultaneously detect 18 metals in serum through inductively coupled plasma-mass spectrometry. Logistic regression models were used to estimate crude or adjusted odds ratios (OR_adj ) with 95% confidence intervals (CIs) for the association between metal levels and gallbladder disease. Among the 18 metals tested, 12 were significantly associated with GBC and six with gallstones (P_corrected < 0.002). Boron, lithium, molybdenum, and arsenic levels were associated with GBC compared to gallstones as well as with gallstones compared to population-based controls. Elevated levels of cadmium, chromium, copper, molybdenum, and vanadium were positively associated with GBC versus gallstones; and the OR_adj for the highest tertile (T3) compared to the lowest tertile (T1) ranged from 1.80 to 7.28, with evidence of dose-response trends (P < 0.05). Arsenic, boron, iron, lithium, magnesium, selenium, and sulfur were inversely associated with GBC, with the T3 versus T1 OR_adj ranging from 0.20 to 0.69. Arsenic, boron, calcium, lithium, molybdenum, and phosphorus were negatively associated with gallstones, with the T3 versus T1 OR_adj ranging from 0.50 to 0.75 (P < 0.05).

Conclusions: Metals were associated with both GBC and gallstones, providing cross-sectional evidence of association across the natural history of disease. Longitudinal studies are needed to evaluate the temporality of metal exposure and gallbladder diseases and to investigate the mechanisms of disease pathogenesis.

FIG. 1.

Mean levels of metals among study population.

FIG. 2.

Odds ratios of gallbladder cancer by metal levels. The bar histograms represent the frequency distribution of each metal in the study sample, including GBC and gallstone patients. The tick marks at the bottom of the histogram in each figure represent the metal levels of GBC patients.

FIG. 3.

Adjusted odds ratios associated with gallbladder cancer by metal levels. Adjusted for age, gender, body mass index, cigarette smoking, alcohol drinking, triglyceride level, and total cholesterol level.

FIG. 4.

Adjusted odds ratios associated with gallstones by metal levels. Adjusted for age, gender, body mass index, cigarette smoking, alcohol drinking, triglyceride level, and total cholesterol level.