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Copper and Melanoma Risk: Results from NHANES 2007–2018 and Mendelian Randomization Analyses

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Abstract

Copper is an essential trace element obtained from food. There is a paucity of observational or prospective studies that have investigated the relationship between copper and melanoma risk. Copper serves as a cofactor for pivotal enzymes involved in mitochondrial respiration, antioxidant defense, and neurotransmitter synthesis. Undoubtedly, copper plays an indispensable role in the initiation and progression of tumors, particularly melanoma; however, further investigations are warranted to elucidate the underlying mechanisms linking copper and melanoma risk. Given the availability of dietary copper and serum copper data in the NHANES database, we conducted an investigation into the association between dietary copper intake and serum copper levels with melanoma risk. We enrolled 26,401 individuals with dietary copper data in the 2007–2018 NHANES database. To mitigate confounding variables, a propensity score matching (PSM) was performed. To assess the association between dietary copper intake and melanoma risk, we employed a multivariate logistic regression analysis before and after PSM. The restricted cubic spline analysis was utilized to determine whether there is a non-linear relationship between dietary copper intake and melanoma risk, with subgroup analysis conducted to determine beneficiaries. Then, those with blood copper data from the enrolled population with dietary copper intake were screened out, and subsequently, multivariate logistic regression models were subsequently constructed to investigate the association between serum copper levels and melanoma risk after PSM. Mendelian analysis was further utilized to validate the results of the NHANES database using serum copper as the exposure factor and melanoma as the outcome variable. The study found that melanoma risk was associated with dietary copper intake before and after PSM, demonstrated by multiple logistic regression. The relationship between dietary copper intake and melanoma risk was non-linear, with a reduced risk observed above approximately 2.5 mg/day, as shown by the RCS. The evidence suggests that an increased intake of copper is linked to a decreased risk of melanoma. To clarify the mechanism behind the increased risk of melanoma due to higher dietary copper intake, we analyzed the population data from the NHANES database on serum copper and dietary copper intake. Our results indicated that there is no causal relationship between serum copper and melanoma risk. Mendelian randomization analysis of multi-database data sources confirmed the conclusion of the NHANES database analysis. Dietary copper is a protective factor against melanoma, and serum copper or blood copper is not associated with melanoma risk. This suggests that serum or blood copper is not responsible for the protective effect of dietary copper intake on melanoma risk, and the mechanisms need to be further investigated.

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Data Availability

Publicly available datasets were analyzed in this study. This data of observational study can be found here: https://www.cdc.gov/nchs/nhanes/. The GWAS data are available through the MRC IEU Open GWAS database (https://gwas.mrcieu.ac.uk/), UK biobank (http://www.nealelab.is/uk-biobank), and the FinnGen consortium round 7 (https://www.finngen.fi/en).

Abbreviations

BMI:

Body mass index

CI:

Confidence interval

IVW:

Inverse-variance weighted

GWAS:

Genome-wide association studies

RCS:

Restricted cubic splines

PSM:

Propensity score matching

OR:

Odds ratio

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Funding

The study was supported by funds from the foundation of National Natural Science Foundation of China (82030082, 82002719 and 82172676), and the foundation of Natural Science Foundation of Shandong (ZR2020LZL014 and ZR2020LZL016). D-WC has received grants from the Young Elite Scientist Sponsorship Program by Cast (no. YESS20210137).

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Author notes

  1. Jia Wang and Juan Wang contributed equally to this work. .

Authors and Affiliations

  1. Shantou University Medical College, Shantou, 515041, Guangdong Province, China

    Jia Wang & Jinming Yu

  2. Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China

    Jia Wang, Juan Wang, Jinming Yu & Dawei Chen

  3. Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan Province, China

    Juan Wang & Jinming Yu

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  1. Jia Wang
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All authors contributed to the study conception and design. D-WC and J-MY designed the study. JW and JW collected the data, conducted the experiments, and drafted the manuscript. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jinming Yu or Dawei Chen.

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Fig. 4

Propensity score matching (PSM) analysis performed for participants with both serum and dietary copper intaking (PNG 58.6 kb)

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Wang, J., Wang, J., Yu, J. et al. Copper and Melanoma Risk: Results from NHANES 2007–2018 and Mendelian Randomization Analyses. Biol Trace Elem Res (2024). https://doi.org/10.1007/s12011-024-04072-0

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