This case-control study compared plasma copper, zinc and copper isotope ratios between Algerian patients with papillary thyroid carcinoma and healthy controls. Patients had higher plasma copper, lower plasma zinc and a higher copper-to-zinc ratio, and their plasma was enriched in the lighter copper isotope. The authors propose these as diagnostic biomarkers; the study does not address where the copper came from.
Key numbers
- Plasma copper, mean ± SD: 1346.1 ± 328.3 µg/L in 46 patients versus 1060.5 ± 216.1 µg/L in 50 controls (p < 0.0001) (abstract; Results, p. 3).
- Plasma zinc: 942.1 ± 205.2 µg/L in patients versus 1027.9 ± 151.4 µg/L in controls (p < 0.05); copper-to-zinc ratio 1.5 ± 0.4 versus 1.0 ± 0.3 (p < 0.0001) (abstract).
- Against a reference range of 804 to 1,620 µg/L: 16% of patients and 0% of controls were at or above 1,620 µg/L; 0% of patients and 14% of controls were at or below 804 µg/L (Table 2, p. 4).
- Control median plasma copper 1,060 µg/L (Results, p. 3).
- Area under the ROC curve 0.81 for the copper-to-zinc ratio and 0.78 for the copper isotope ratio (Results, p. 4).
Methods (brief)
Heparinized plasma was analyzed for total copper and zinc by total reflection X-ray fluorescence with a gallium internal standard and a Seronorm serum control (inter-assay CV below 15%). Copper isotope ratios in plasma and tumor tissue were measured by multicollector ICP-MS after column separation. Groups were compared by t-test or Mann-Whitney test.
Evidence fitness
Supports plasma copper values in a North African adult population and the observation that copper status is altered in thyroid cancer. It is a disease-biomarker study: it does not measure dietary or environmental copper exposure and cannot show that copper causes thyroid cancer.
Limitations
Hospital-based recruitment without specific exclusion criteria, 91% women among patients, and a single region. The higher plasma copper in patients may reflect disease processes such as inflammation rather than intake. Total reflection X-ray fluorescence has a wider inter-assay variation than ICP-MS.
Related evidence
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