The role of cobalt exposure in the incidence of cancer: a systematic review and meta-analysis

Cobalt is widely used in industrial processes, resulting in occupational exposure among workers in mining, smelting, and hard-metal industries. Although cobalt-containing compounds have been classified as carcinogenic or possibly carcinogenic, epidemiological evidence linking cobalt exposure to cancer risk remains limited and heterogeneous. This systematic review aimed to synthesize the available human evidence on the association between cobalt exposure and site-specific cancer outcomes. A systematic search of PubMed, Web of Science, and Scopus was conducted to identify epidemiological studies examining occupational or environmental cobalt exposure and cancer incidence or mortality. Observational studies reporting standardized mortality ratios (SMRs), standardized incidence ratios (SIRs), or comparable effect estimates were eligible. Due to substantial heterogeneity in exposure assessment, outcome definitions, and study design, quantitative synthesis was restricted to selected site-specific cancer outcomes reported in at least two cohort studies. Random-effects models were applied where appropriate. Other outcomes were summarized narratively. Heterogeneity was explored descriptively, and publication bias was assessed cautiously using funnel plots, Egger’s and Begg’s tests, and trim-and-fill analysis, acknowledging limited statistical power. Four occupational cohort studies met the inclusion criteria, contributing 25 site-specific effect estimates across a range of cancer outcomes. Consistently elevated SMRs were observed for respiratory cancers, particularly malignancies of the lung, bronchus, and trachea, across multiple cohorts of cobalt-exposed workers. For other cancer sites, including leukemia, esophageal cancer, lip cancer, and cancers of the upper aerodigestive tract, increased point estimates were reported in individual studies; however, these findings were based on single studies and were not quantitatively pooled. Considerable heterogeneity was observed across cancer sites and studies, reflecting differences in exposure characteristics, co-exposures, and outcome definitions. Formal tests did not indicate strong evidence of publication bias, but interpretation was limited by the small number of studies. The available epidemiological evidence suggests an elevated observed mortality from respiratory cancers among workers exposed to cobalt in occupational settings. However, the small number of studies, substantial heterogeneity, and limitations in exposure assessment preclude definitive causal inference. The findings should be interpreted as exploratory and hypothesis-generating. Further well-designed longitudinal studies with improved quantitative exposure assessment, site-specific cancer outcomes, and careful control of confounding are needed to clarify the carcinogenic potential of cobalt exposure.