Gallbladder cancer affects northern and eastern India at high rates, and a Nature-published case-control study links this malignancy to serum trace element profiles.
Researchers enrolled 912 cases and 1140 controls at Tata Memorial Hospital to measure non-essential and essential metals using ICP-MS.
- Exposure to a metal mixture increased gallbladder cancer risk by an odds ratio of 6.19 per unit increase in the WQS index.
- Copper contributed approximately 60% of the highest weight in the metal mixture, followed by cadmium at 26% and manganese at 13%.
- An exploratory mediation analysis found no statistically significant evidence of mediation through gallstones, with a beta ACME of 0.01.
Researchers collected serum samples after acid digestion with trace metal-grade nitric acid at a 50-fold dilution. The study measured non-essential elements including chromium, nickel, arsenic, cadmium, lead, and uranium. Essential elements evaluated in the patient samples comprised manganese, copper, and selenium.
Distributions of trace element concentrations were highly right-skewed and required log-transformation for statistical and sensitivity analysis. Individual effects emerged from a logistic regression model adjusted for prespecified confounders. Joint metal mixture effects utilized weighted quantile sum and quantile g-computation methods.
| Trace Element | Element Classification | Mixture Weight Contribution |
|---|---|---|
| Copper (Cu) | Essential | ~ 60% |
| Cadmium (Cd) | Non-essential | ~ 26% |
| Manganese (Mn) | Essential | ~ 13% |
A strong non-linear association appeared for copper, manganese, cadmium, and uranium with a P-overall value of 0.05 or lower and a P-nonlinear value of 0.05 or lower. The strongest inter-metal correlation in the cohort occurred between manganese and uranium. Two-part and winsorization models confirmed the robustness of these primary findings alongside the logistic regression.
An internal validation dataset generated from a training-validation split applied a directed acyclic graph-informed confounder set. This confirmed an association between the weighted quantile sum index and gallbladder cancer risk with an odds ratio of 2.71.
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