Serum trace element profiles and gallbladder cancer risk in an Indian population: evidence from a case–control study

Gallbladder cancer (GBC), a rare yet aggressive biliary tract malignancy, varies by geographic location, with greater incidence in the north and northeast of India along the Gangetic belt, suggesting that environmental risk factors may contribute to disease etiology. A total of 912 GBC cases and 1140 visitor controls were enrolled at Tata Memorial Centre, India. The concentration of non-essential (Cr, Ni, As, Cd, Pb, U) and essential metals (Mn, Cu, Se) were measured using the inductively coupled plasma mass spectrometer (ICPMS). Individual metal effects were presented using logistic regression model adjusting for confounders, while joint metal mixture effects were obtained using weighted quantile sum and quantile g-computation methods. A strong J-shaped non-linear association for Cu (OR = 10.21; p-value ≤ 0.005) and Cd (OR = 4.79; p-value ≤ 0.005) was observed. The strongest inter-metal correlation was observed for Mn-U. Exposure to metal mixture showed one-unit increase in the WQS index with increased GBC risk (OR = 6.19; p-value < 0.00001), with the highest weight contributed by Cu (~ 60%), followed by Cd (~ 27%) and Mn (~ 13%). Metal mixtures play a significant carcinogenic role in the development of GBC. Identification of the source of exposure, particularly in the high-risk areas of the GBC, would be useful in primary prevention.