<![CDATA[Colorectal cancer (CRC) is a major contributor to global cancer morbidity and mortality, with heavy metal exposure increasingly implicated in its development. Several studies report differences in blood heavy metal profiles between CRC patients and healthy individuals, yet clinical relevance to surgical and chemotherapeutic outcomes remains unclear. This systematic review, guided by the Vogelstein multistep carcinogenesis model, evaluated blood and tissue heavy metal concentrations in CRC patients and their association with clinical response to surgery and chemotherapy. Evidence was synthesized from 19 primary studies (2016-2026) directly measuring heavy metal or trace element concentrations in CRC patients, supplemented by contextual clinical and mechanistic literature. Findings reveal consistent differences in heavy metal profiles between CRC patients and healthy controls, linked to tumor characteristics and molecular pathways such as WNT/beta-catenin and CD44v6 implicated in treatment resistance. Only three of the 19 primary studies measured metal status alongside a clinical or treatment-related outcome in the same patients: serum zinc and chemotherapy tolerability, prediagnostic selenium and mortality, and prediagnostic arsenic and CRC risk, the last a null finding. Remaining evidence consists of separate streams describing metal profiles, clinicopathological associations, and molecular resistance mechanisms without directly linking exposure to outcome. These findings support a hypothesis that blood heavy metal concentrations may serve as supplementary indicators of clinical heterogeneity in CRC, but do not establish a demonstrated clinical association; reverse causation cannot be excluded given the predominantly cross-sectional and case-control designs reviewed. Prospective cohort studies with pre-treatment sampling are needed before any biomarker role can be considered.]]>
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