Cadmium in biological samples and site-specific cancer risk and mortality: A systematic review of original articles and meta-analyses

Background: Cadmium (Cd) is classified as a class 1 carcinogen by the IARC, yet uncertainty persists regarding the total burden of cancer (incidence and mortality) caused by exposure to it, due to the still limited evidence with regard to its aetiological role in cancer at several body sites. Objectives and methods: We searched PubMed and EMBASE for meta-analyses and original articles published by February 1st, 2024, that focused on the link between cadmium measured in biological samples (blood, urine, finger-/toe-nails, and hair) and site-specific cancer risk and mortality. Results: We included 9 meta-analyses and 57 original articles (of these, the design was retrospective in 38 and prospective in 19, and Cd levels were quantified in blood, n=33, urine, n=19, both blood and urine, n=2, or finger-/toenail, n=3). Current data consistently suggest a causal role of exposure to cadmium in pancreas, lung, and bladder carcinogenesis. Total cancer risk and mortality are also positively correlated with Cd levels in biological samples. The evidence is weak or inconclusive for the remaining cancer sites (including breast and prostate), mostly due to the limited number of studies available to date and/or methodological limitations. Discussion: Exposure to cadmium poses a risk for increased cancer incidence and mortality. Cadmium-related cancer burden might indeed be currently underestimated, as the amount of available evidence for most cancer sites and types is currently limited, and more research in the field is warranted. Continuing efforts to contain Cd pollution and mitigate associated health risk are also needed.