Blood Trace Elements in Association with Esophageal Squamous Cell Carcinoma Risk, Aggressiveness and Prognosis in a High Incidence Region of China

Overview

Journal Sci Rep

Specialty Science

Date 2025 Feb 12

PMID 39939385

Authors

Shuyi Qiu

Bingmeng Xie

Jiahui Liao

Jianan Luo

Xi Liu

Lihua He

Yiteng Huang

Lin Peng

Affiliations

Soon will be listed here.

Abstract

Toxic elements exposure and imbalance in essential element homeostasis remain incomprehensive in esophageal squamous cell carcinoma (ESCC) carcinogenesis, especially in tumor progression. To reveal the toxic and essential elements inside body associated with ESCC occurrence, aggressive features and outcomes, whole blood concentrations of eight trace elements were quantified in 150 ESCC cases and 177 controls using inductively coupled plasma-mass spectrometry (ICP-MS). Concentrations of cadmium (Cd), lead (Pb), chromium (Cr), copper (Cu), arsenic (As), and selenium (Se) showed significant differences between the case and control subjects. The restricted cubic spline (RCS) analysis showed As, Zinc (Zn), and manganese (Mn) was linked with ESCC risk in a U-shaped pattern, whereas an inverted U-shaped curve for Cd (all P-non-linear < 0.05). Contrary to Se, the elements Pb, Cr and Cu were positively associated with ESCC risk. By Bayesian Kernel Machine Regression models, the mixtures of the eight trace elements were found to be significantly associated with ESCC risk and metastasis, with Cr, Mn, Cu, Zn, and Pb having a PIP of 1.000 for occurrence risk and Mn being the main contributor for metastatic risk (PIP = .6570). The weighted quantile sum (WQS) model consistently showed that Cu, Cr, Pb, and Cd ranked as the top four positive elements for ESCC risk. Multivariable logistic regression analysis indicated Pb and As were positively associated with tumor invasion (adjusted OR 3.024 [1.053-8.689]; OR 4.385 [1.271-15.126], respectively), whereas Se had the opposite trend (adjusted OR 0.261 [0.074-0.927). Patients with high Cr, Mn, or Pb showed worse overall survival (OS), and high Mn were linked to inferior progression-free survival (PFS) (all P < 0.05). Zn and Pb, and Mn and Cu were identified as independent prognostic factors for OS and PFS, respectively. This study suggests trace element disbalance in human body contributes to the risk of onset and progression of ESCC, especially in a high-incidence region. Further epidemiological and experimental studies were needed to clarify the probable pathogenic processes underpinning the potential link between trace element mixtures and ESCC.

References

Zhang Q, Pan E, Liu L, Hu W, He Y, Xu Q . Study on the relationship between manganese concentrations in rural drinking water and incidence and mortality caused by cancer in Huai'an city. Biomed Res Int. 2014; 2014:645056. PMC: 4235228. DOI: 10.1155/2014/645056. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Parviainen A, Vazquez-Arias A, Arrebola J, Martin-Peinado F . Human health risks associated with urban soils in mining areas. Environ Res. 2021; 206:112514. DOI: 10.1016/j.envres.2021.112514. View

Yao T, Jiang S, Hou K, Sun H, Wang H . Cadmium (Cd) accumulation in traditional Chinese medicine materials (TCMMs): A critical review. Ecotoxicol Environ Saf. 2022; 242:113904. DOI: 10.1016/j.ecoenv.2022.113904. View

Manton W, Rothenberg S, Manalo M . The lead content of blood serum. Environ Res. 2001; 86(3):263-73. DOI: 10.1006/enrs.2001.4271. View

Guo Y, Yang G, Dong Q, Huang C . [Distribution of heavy metals in soils from the typical regions of Shantou and their environmental pollution assessment]. Huan Jing Ke Xue. 2007; 28(5):1067-74. View

Uhlenhopp D, Then E, Sunkara T, Gaduputi V . Epidemiology of esophageal cancer: update in global trends, etiology and risk factors. Clin J Gastroenterol. 2020; 13(6):1010-1021. DOI: 10.1007/s12328-020-01237-x. View

Milne D, SIMS R, Ralston N . Manganese content of the cellular components of blood. Clin Chem. 1990; 36(3):450-2. View

Zhang J, Wang G, Huang A, Cao K, Tan W, Geng H . Association between Serum Level of Multiple Trace Elements and Esophageal Squamous Cell Carcinoma Risk: A Case-Control Study in China. Cancers (Basel). 2022; 14(17). PMC: 9455051. DOI: 10.3390/cancers14174239. View

10.

Archanjo A, Leone Evangelista Monteiro de Assis A, de Oliveira M, Mendes S, Borcoi A, de Lima Maia L . Elemental characterization of oral cavity squamous cell carcinoma and its relationship with smoking, prognosis and survival. Sci Rep. 2020; 10(1):10382. PMC: 7316707. DOI: 10.1038/s41598-020-67270-5. View

11.

Dominguez-Alvarez E, Racz B, Marc M, Nasim M, Szemeredi N, Viktorova J . Selenium and tellurium in the development of novel small molecules and nanoparticles as cancer multidrug resistance reversal agents. Drug Resist Updat. 2022; 63:100844. DOI: 10.1016/j.drup.2022.100844. View

12.

Zhong Y, Yang C, Wang N, Pan D, Wang S, Sun G . Hot Tea Drinking and the Risk of Esophageal Cancer: A Systematic Review and Meta-Analysis. Nutr Cancer. 2021; 74(7):2384-2391. DOI: 10.1080/01635581.2021.2007963. View

13.

Zhang W, Yan S, Liu M, Zhang G, Yang S, He S . beta-Catenin/TCF pathway plays a vital role in selenium induced-growth inhibition and apoptosis in esophageal squamous cell carcinoma (ESCC) cells. Cancer Lett. 2010; 296(1):113-22. DOI: 10.1016/j.canlet.2010.04.001. View

14.

Fong L, Huebner K, Jing R, Smalley K, Brydges C, Fiehn O . Zinc treatment reverses and anti-Zn-regulated miRs suppress esophageal carcinomas in vivo. Proc Natl Acad Sci U S A. 2023; 120(20):e2220334120. PMC: 10193985. DOI: 10.1073/pnas.2220334120. View

15.

Chanihoon G, Afridi H, Kazi T, Talpur F, Baig J . Evaluation of zinc and cadmium levels in the biological samples of Ewing sarcomas patients and healthy subjects. Clin Chim Acta. 2021; 522:1-7. DOI: 10.1016/j.cca.2021.08.002. View

16.

Rozenberg J, Kamynina M, Sorokin M, Zolotovskaia M, Koroleva E, Kremenchutckaya K . The Role of the Metabolism of Zinc and Manganese Ions in Human Cancerogenesis. Biomedicines. 2022; 10(5). PMC: 9139143. DOI: 10.3390/biomedicines10051072. View

17.

Zhong L, Li H, Chang W, Ao Y, Wen Z, Chen Y . TP53 Mutations in Esophageal Squamous Cell Carcinoma. Front Biosci (Landmark Ed). 2023; 28(9):219. DOI: 10.31083/j.fbl2809219. View

18.

Rodriguez-Tomas E, Baiges-Gaya G, Castane H, Arenas M, Camps J, Joven J . Trace elements under the spotlight: A powerful nutritional tool in cancer. J Trace Elem Med Biol. 2021; 68:126858. DOI: 10.1016/j.jtemb.2021.126858. View

19.

Bray F, Laversanne M, Sung H, Ferlay J, Siegel R, Soerjomataram I . Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024; 74(3):229-263. DOI: 10.3322/caac.21834. View

20.

Hashemian M, Murphy G, Etemadi A, Poustchi H, Brockman J, Kamangar F . Toenail mineral concentration and risk of esophageal squamous cell carcinoma, results from the Golestan Cohort Study. Cancer Med. 2017; 6(12):3052-3059. PMC: 5727321. DOI: 10.1002/cam4.1247. View