Top

Published in:

Open Access 01-12-2024 | Research

Effect of trace element mixtures on the outcome of patients with esophageal squamous cell carcinoma: a prospective cohort study in Fujian, China

Authors: Kaili Yu, Shuang Liu, Zheng Lin, Jianyu Song, Qiaoyan Zeng, Jinsong Zhou, Juwei Zhang, Suhong Zhang, Jianbo Lin, Zhisheng Xiang, Zhijian Hu

Published in: BMC Cancer | Issue 1/2024

Abstract

Background

The evidence about the effects of trace elements on overall survival(OS) of patients with esophageal squamous cell carcinoma(ESCC) is limited. This study aims to evaluate mixed effects of plasma trace elements on OS of ESCC.

Methods

This prospective cohort analysis included 497 ESCC patients with a median follow-up of 52.3 months. The concentrations of 17 trace elements were measured. We fitted Cox’s proportional hazards regression, factor analysis and Bayesian kernel machine regression (BKMR) models to estimate the association between trace elements and OS.

Results

Our analysis found that in the single-element model, Co, Ni, and Cd were associated with an increased risk of death, while Ga, Rb, and Ba were associated with a decreased risk. Cd had the strongest risk effect among all elements. As many elements were found to be mutually correlated, we conducted a factor analysis to identify common factors and investigate their associations with survival time. The factor analysis indicated that the factor with high factor loadings in Ga, Ba and B was linked to a decreased risk of death, while the factor with high factor loadings in Co, Ti, Cd and Pb was associated with a borderline significantly increased risk. Using BKMR analysis to disentangle the interaction between elements in significant factors, we discovered that Ga interacted with Ba and both elements had U-shaped effects with OS. Cd, on the other hand, had no interaction with other elements and independently increased the risk of death.

Conclusions

Our analysis revealed that Ga, Ba and Cd were associated with ESCC outcome, with Ga and Ba demonstrating an interaction. These findings provide new insights into the impact of trace elements on the survival of patients with ESCC.

Available only for authorised users

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49. https://doi.org/10.3322/caac.21660.CrossRefPubMed

Yang YM, Hong P, Xu WW, He QY, Liu B. Advances in targeted therapy for esophageal cancer. Signal Transduct Target Ther. 2020;5:229. https://doi.org/10.1038/s41392-020-00323-3.CrossRefPubMedPubMedCentral

Sihvo E, Helminen O, Gunn J, Sipilä J, Rautava P, Kytö V. Long-term outcomes following minimally invasive and open esophagectomy in Finland: A population-based study. Eur J Surg Oncol. 2019;45:1099–104. https://doi.org/10.1016/j.ejso.2018.12.001.CrossRefPubMed

Yang CS, Chen XL. Research on esophageal cancer: With personal perspectives from studies in China and Kenya. Int J Cancer. 2020;149:264–76. https://doi.org/10.1002/ijc.33421.CrossRefPubMedPubMedCentral

Golonka R, Xiao X, Abokor A, Joe B, Vijay-Kumar M. Altered nutrient status reprograms host inflammation and metabolic health via gut microbiota. J Nutr Biochem. 2020;80:108360–75. https://doi.org/10.1016/j.jnutbio.2020.108360.CrossRefPubMedPubMedCentral

Hughes D, Fedirko V, Jenab M, Schomburg L, Méplan C, Freisling H, et al. Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort. Int J Cancer. 2015;136:1149–61. https://doi.org/10.1002/ijc.29071.CrossRefPubMed

Feng Y, Zeng J, Ma Q, Zhang S, Tang J, Feng J. Serum copper and zinc levels in breast cancer: A meta-analysis. J Trace Elem Med Biol. 2020;62:126629–40. https://doi.org/10.1016/j.jtemb.2020.126629.CrossRefPubMed

Wang Y, Sun Z, Li A, Zhang Y. Association between serum zinc levels and lung cancer: a meta-analysis of observational studies. World J Surg Oncol. 2019;17:78. https://doi.org/10.1186/s12957-019-1617-5.CrossRefPubMedPubMedCentral

Lossow K, Schwarz M, Kipp AP. Are trace element concentrations suitable biomarkers for the diagnosis of cancer? Redox Biol. 2021;42:7. https://doi.org/10.1016/j.redox.2021.101900.CrossRef

10.

Wang Y, Yu L, Ding J, Chen Y. Iron Metabolism in Cancer. Int J Mol Sci. 2018;20:95. https://doi.org/10.3390/ijms20010095.CrossRefPubMedPubMedCentral

11.

Genchi G, Carocci A, Lauria G, Sinicropi M, Catalano A. Nickel: Human Health and Environmental Toxicology. Int J Environ Res Public Health. 2020;17:679–99. https://doi.org/10.3390/ijerph17030679.CrossRefPubMedPubMedCentral

12.

Demircan K, Bengtsson Y, Sun Q, Brange A, Vallon-Christersson J, Rijntjes E, et al. Serum selenium, selenoprotein P and glutathione peroxidase 3 as predictors of mortality and recurrence following breast cancer diagnosis: A multicentre cohort study. Redox Biol. 2021;47: 102145. https://doi.org/10.1016/j.redox.2021.102145.CrossRefPubMedPubMedCentral

13.

Pietrzak S, Wójcik J, Baszuk P, Marciniak W, Lener MR. Influence of the Levels of Arsenic, Cadmium, Mercury and Lead on Overall Survival in Lung Cancer. Biomolecules. 2021;11:1160–71. https://doi.org/10.3390/biom11081160.CrossRefPubMedPubMedCentral

14.

He Y, Peng L, Huang Y, et al. Blood cadmium levels associated with short distant metastasis-free survival time in invasive breast cancer. Environ Sci Pollut Res Int. 2017;24:28055–64. https://doi.org/10.1007/s11356-017-0412-5.CrossRefPubMed

15.

Du T, Huang W, Zheng S, Bao M, Huang Y, Li A, et al. Blood Cadmium Level Is Associated with Short Progression-Free Survival in Nasopharyngeal Carcinoma. Int J Environ Res Public Health. 2019;16:2952–67. https://doi.org/10.3390/ijerph16162952.CrossRefPubMedPubMedCentral

16.

Coker E, Chevrier J, Rauch S, Bradman A, Obida M, Crause M, et al. Association between prenatal exposure to multiple insecticides and child body weight and body composition in the VHEMBE South African birth cohort. Environ Int. 2018;113:122–32. https://doi.org/10.1016/j.envint.2018.01.016.CrossRefPubMedPubMedCentral

17.

Rahimzadeh Mehrdad R, Rahimzadeh Mehravar R, Kazemi S, Moghadamnia A. Cadmium toxicity and treatment: An update. Caspian J Intern Med. 2017; 8: 135–145. https://doi.org/10.22088/cjim.8.3.135.

18.

Lim JT, Yue QT, Valeri L, Lee J, WEI JS. Association between serum heavy metals and prostate cancer risk - A multiple metal analysis. Environ Int. 2019; 132: 105109–105118. https://doi.org/10.1016/j.envint.2019.105109.

19.

Ganguly K, Levänen B, Palmberg L, Åkesson A, Lindén A. Cadmium in tobacco smokers: a neglected link to lung disease? Eur Respir Rev. 2018;27:170122–9. https://doi.org/10.1183/16000617.0122-2017.CrossRefPubMedPubMedCentral

20.

Nemmiche S. Oxidative Signaling Response to Cadmium Exposure. Toxicol Sci. 2017;156:4–10. https://doi.org/10.1093/toxsci/kfw222.CrossRefPubMed

21.

Lener M, Reszka E, Marciniak W, Lesicka M, Baszuk P, Jabłońska E, et al. Blood cadmium levels as a marker for early lung cancer detection. J Trace Elem Med Biol. 2021;64:126682–6. https://doi.org/10.1016/j.jtemb.2020.126682.CrossRefPubMed

22.

VRD A, DRWB C, ASB C, NB D, DK A, SM A, et al. Environmental cadmium exposure and pancreatic cancer: Evidence from case control, animal and in vitro studies - ScienceDirect. Environ Int. 2019; 128: 353-361. https://doi.org/10.1016/j.envint.2019.04.048.

23.

Song JK, Luo H, Yin XH, Huang GL, Luo SY, Lin DR, et al. Association between cadmium exposure and renal cancer risk: a meta-analysis of observational studies. Sci Rep. 2015;5:17976–83. https://doi.org/10.1038/srep17976.CrossRefPubMedPubMedCentral

24.

Larsson S, Wolk A. Urinary cadmium and mortality from all causes, cancer and cardiovascular disease in the general population: systematic review and meta-analysis of cohort studies. Int J Epidemiol. 2016;45:782–91. https://doi.org/10.1093/ije/dyv086.CrossRefPubMed

25.

Watanabe Y, Nogawa K, Nishijo M, Sakurai M, Ishizaki M, Morikawa Y, et al. Relationship between cancer mortality and environmental cadmium exposure in the general Japanese population in cadmium non-polluted areas. Int J Hyg Environ Health. 2020;223:65–70. https://doi.org/10.1016/j.ijheh.2019.10.005.CrossRefPubMed

26.

Nair A, Degheselle O, Smeets K, Van Kerkhove E, Cuypers A. Cadmium-Induced Pathologies: Where Is the Oxidative Balance Lost (or Not)? Int J Mol Sci. 2013;14:6116–43. https://doi.org/10.3390/ijms14036116.CrossRefPubMedPubMedCentral

27.

Genchi G, Sinicropi M, Lauria G, Carocci A, Catalano A. The Effects of Cadmium Toxicity. Int J Environ Res Public Health. 2020;17:2782–805. https://doi.org/10.3390/ijerph17113782.CrossRef

28.

Wallace D, Spandidos D, Tsatsakis A, Schweitzer A, Djordjevic V, Djordjevic A. Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer. Int J Mol Med. 2019; 44: 145–156.https://doi.org/10.3892/ijmm.2019.4204.

29.

Pizzino G, Bitto A, Interdonato M, Galfo F, Irrera N, Mecchio A, et al. Oxidative stress and DNA repair and detoxification gene expression in adolescents exposed to heavy metals living in the Milazzo-Valle del Mela area (Sicily, Italy). Redox Biol. 2014;2:686–93. https://doi.org/10.1016/j.redox.2014.05.003.CrossRefPubMedPubMedCentral

30.

Straus D. Gallium nitrate in the treatment of lymphoma. Semin Oncol. 2003;30:25–33. https://doi.org/10.1016/s0093-7754(03)00173-8.CrossRefPubMed

31.

Stadler W, Kuzel T, Raghavan D, Levine E, Vogelzang N, Roth B, et al. Metastatic bladder cancer: advances in treatment. Eur J Cancer. 1997;33 Suppl 1:S23-S26. https://doi.org/10.1016/s0959-8049(96)00337-1.

32.

Chitambar C. Gallium-containing anticancer compounds. Future Med Chem. 2012;4:1257–72. https://doi.org/10.4155/fmc.12.69.CrossRefPubMed

33.

Hart M, Adamson R. Antitumor activity and toxicity of salts of inorganic group 3a metals: aluminum, gallium, indium, and thallium. Proc Natl Acad Sci USA. 1971;68:1623–6. https://doi.org/10.1073/pnas.68.7.1623.CrossRefPubMedPubMedCentral

34.

Chitambar C. Gallium Complexes as Anticancer Drugs. Met Ions Life Sci. 2018;18:281–301. https://doi.org/10.1515/9783110470734-016.CrossRef

35.

Chitambar C. Gallium and its competing roles with iron in biological systems. Biochem Biophys Acta. 2016;1863:2044–53. https://doi.org/10.1016/j.bbamcr.2016.04.027.CrossRefPubMed

36.

Chitambar C, Wereley J, Matsuyama S. Gallium-induced cell death in lymphoma: role of transferrin receptor cycling, involvement of Bax and the mitochondria, and effects of proteasome inhibition. Mol Cancer Ther. 2006;5:2834–43. https://doi.org/10.1158/1535-7163.Mct-06-0285.CrossRefPubMed

37.

Alhajala H, Markley J, Kim J, AL-Gizawiy M, Schmainda K, Kuo J, et al. The cytotoxicity of gallium maltolate in glioblastoma cells is enhanced by metformin through combined action on mitochondrial complex 1. Oncotarget 2020; 11: 1531–1544. https://doi.org/10.18632/oncotarget.27567.

38.

Behmoaras J. The versatile biochemistry of iron in macrophage effector functions. FEBS J. 2021;288:6972–89. https://doi.org/10.1111/febs.15682.CrossRefPubMed

39.

Zoroddu M, Aaseth J, Crisponi G, Medici S, Peana M, Nurchi V. The essential metals for humans: a brief overview. J Inorg Biochem. 2019;195:120–9. https://doi.org/10.1016/j.jinorgbio.2019.03.013.CrossRefPubMed

40.

Peana M, Medici S, Dadar M, Zoroddu M, Pelucelli A, Chasapis C, et al. Environmental barium: potential exposure and health-hazards. Arch Toxicol. 2021;95:2605–12. https://doi.org/10.1007/s00204-021-03049-5.CrossRefPubMed

41.

He J, Li G, Zhu Z, Hu M, Wu H, Zhu J, et al. Associations of exposure to multiple trace elements with the risk of goiter: A case-control study. Environ Pollut. 2021;288:117739–47. https://doi.org/10.1016/j.envpol.2021.117739.CrossRefPubMed

Title: Effect of trace element mixtures on the outcome of patients with esophageal squamous cell carcinoma: a prospective cohort study in Fujian, China
Authors: Kaili Yu
Shuang Liu
Zheng Lin
Jianyu Song
Qiaoyan Zeng
Jinsong Zhou
Juwei Zhang
Suhong Zhang
Jianbo Lin
Zhisheng Xiang
Zhijian Hu
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-023-11763-9

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2024

Radiation-induced upregulation of FGL1 promotes esophageal squamous cell carcinoma metastasis via IMPDH1

Correction: How should the healthcare system support cancer survivors? Survivors’ and health professionals’ expectations and perception on comprehensive cancer survivorship care in Korea: a qualitative study

ESCO2’s oncogenic role in human tumors: a pan-cancer analysis and experimental validation

Correction: Oncological risk of proximal gastrectomy for proximal advanced gastric cancer after neoadjuvant chemotherapy

Differential efficacy of tyrosine kinase inhibitors according to the types of EGFR mutations and agents in non-small cell lung cancer: a real-world study

Using a combination of superb microvascular imaging and other auxiliary ultrasound techniques to increase the accuracy of gray-scale ultrasound for breast masses

Keynote webinar | Spotlight on antibody–drug conjugates in cancer