Abstract
Background
Growing evidence suggests that environmental factors probably play important roles in the development of gastroesophageal cancers (GOC), however, the effects of trace elements on GOC remain unclear.
Objective
To assess the effect of trace elements on GOC and the effect modification by other factors.
Methods
Hair and fingernail samples were collected from GOC cases and controls in a population-based case-control study in Taixing, China, and were used to detect the concentrations of 12 trace elements using inductively coupled plasma mass spectrometry. Unconditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for concentrations of 12 trace elements in association with GOC after adjusting the other factors.
Results
A total of 830 hair samples (581 controls and 249 cases) and 895 fingernail samples (559 controls and 336 cases) were included. Compared to the lowest-tertile concentration, the higher tertiles of Ca, Zn, Fe, Al, Cr, Pb, Se, and V were positively associated with GOC, while the higher tertiles of Mg, Mn, Sr, and As were inversely associated with GOC. Significant interactions between the hair level of Cr and two other risk factors, including smoking (P for interaction = 0.044) and alcohol drinking (P for interaction = 0.028), were observed in association with GOC.
Significance
The current study reveals that these 12 trace elements in hair and fingernails are associated with GOC to varying degrees. Further studies and animal experiments are needed to clarify the associations and explore potential mechanisms.
Impact statement
The role of trace elements in the development or inhibition of gastroesophageal cancers (GOC) remains unclear. In this study, we further explored the associations between 12 trace elements and GOC based on a population-based case-control study conducted in Taixing, China. Higher levels of Ca, Zn, Fe, Al, Cr, Pb, Se, and V were positively associated with increased GOC, while inverse associations between higher levels of Mg, Mn, Sr, As, and GOC were observed. Observed associations were consistent in hair and fingernail samples. Moreover, interaction effects between hair level of Cr and smoking or alcohol drinking were identified.
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Data availability
The datasets and code used and analyzed during the current study are available from the corresponding author upon reasonable request.
References
Yeo ST, Bray N, Haboubi H, Hoare Z, Edwards RT. Endoscopic ultrasound staging in patients with gastro-oesophageal cancers: a systematic review of economic evidence. BMC Cancer. 2019;19:900.
Johnson IT. Understanding the association between diet and nutrition in upper gastrointestinal cancer. Expert Rev Gastroenterol Hepatol. 2015;9:1347–9.
Pasha Q, Malik SA, Shaheen N, Shah MH. Investigation of trace metals in the blood plasma and scalp hair of gastrointestinal cancer patients in comparison with controls. Clin Chim Acta. 2010;411:531–9.
Kayamba V. Nutrition and upper gastrointestinal cancers: an overview of current understandings. Semin Cancer Biol. 2022;83:605–16.
Türkdoğan MK, Karapinar HS, Kilicel F. Serum trace element levels of gastrointestinal cancer patients in an endemic upper gastrointestinal cancer region. J Trace Elem Med Biol. 2022;72:126978.
Tully J, DeSantis MK, Schock MR. Water quality-pipe deposit relationships in Midwestern lead pipes. AWWA Water Sci. 2019;1:e1127.
Harmon SM, Tully J, DeSantis MK, Schock MR, Triantafyllidou S, Lytle DA. A holistic approach to lead pipe scale analysis: Importance, methodology, and limitations. AWWA Water Sci. 2022;4:e1278.
Bae Y, Pasteris JD, Giammar DE. The ability of phosphate to prevent lead release from pipe scale when switching from free chlorine to monochloramine. Environ Sci Technol. 2020;54:879–88.
Li G, Bae Y, Mishrra A, Shi B, Giammar DE. Effect of aluminum on lead release to drinking water from scales of corrosion products. Environ Sci Technol. 2020;54:6142–51.
Bae Y, Pasteris JD, Giammar DE. Impact of iron-rich scale in service lines on lead release to water. AWWA Water Sci. 2020;2:e1188.
Doré E, Deshommes E, Laroche L, Nour S, Prévost M. Lead and copper release from full and partially replaced harvested lead service lines: Impact of stagnation time prior to sampling and water quality. Water Res. 2019;150:380–91.
Wang Y, Ou YL, Liu YQ, Xie Q, Liu QF, Wu Q, et al. Correlations of trace element levels in the diet, blood, urine, and feces in the Chinese male. Biol Trace Elem Res. 2012;145:127–35.
Skalny AV, Serebryansky EP, Korobeinikova TV, Tsatsakis A, Vardavas C, Paoliello MMB, et al. Smoking is associated with altered serum and hair essential metal and metalloid levels in women. Food Chem Toxicol. 2022;167:113249.
Nawi AM, Chin SF, Mazlan L, Jamal R. Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements. Sci Rep. 2020;10:18670.
Sohrabi M, Nikkhah M, Sohrabi M, Rezaee Farimani A, Mirasgari Shahi M, Ziaie H, et al. Evaluating tissue levels of the eight trace elements and heavy metals among esophagus and gastric cancer patients: a comparison between cancerous and non-cancerous tissues. J Trace Elem Med Biol. 2021;68:126761.
Juloski JT, Rakic A, Ćuk VV, Ćuk VM, Stefanović S, Nikolić D, et al. Colorectal cancer and trace elements alteration. J Trace Elem Med Biol. 2020;59:126451.
Navarro Silvera SA, Rohan TE. Trace elements and cancer risk: a review of the epidemiologic evidence. Cancer Causes Control. 2007;18:7–27.
O’Rorke MA, Cantwell MM, Abnet CC, Brockman AJ, Murray LJ. Toenail trace element status and risk of Barrett’s oesophagus and oesophageal adenocarcinoma: results from the FINBAR study. Int J Cancer. 2012;131:1882–91.
Smith D, Hernandez-Avila M, Téllez-Rojo MM, Mercado A, Hu H. The relationship between lead in plasma and whole blood in women. Environ Health Perspect. 2002;110:263–8.
Jacobson TA, Kler JS, Bae Y, Chen J, Ladror DT, Iyer R, et al. A state-of-the-science review and guide for measuring environmental exposure biomarkers in dried blood spots. J Expo Sci Environ Epidemiol. 2022:1–19. https://doi.org/10.1038/s41370-022-00460-7.
Funk WE, McGee JK, Olshan AF, Ghio AJ. Quantification of arsenic, lead, mercury and cadmium in newborn dried blood spots. Biomarkers 2013;18:174–7.
Lin Y, Wu C, Yan W, Guo S, Liu B. Five serum trace elements associated with risk of cardia and noncardia gastric cancer in a matched case-control study. Cancer Manag Res. 2020;12:4441–51.
Aslan A, Karapinar HS, Kilicel F, Boyacıoğlu T, Pekin C, Toprak ŞS, et al. Trace element levels in serum and gastric mucosa in patients with Helicobacter pylori positive and negative gastritis. J Trace Elem Med Biol. 2023;75:127108.
National Toxicology Program (NTP). Report on Carcinogens, Fifteenth Edition. Research Triangle Park, NC: U.S. Department of Health and Human Services, Public Health Service. 2021. http://ntp.niehs.nih.gov/go/roc15/.
Igbokwe IO, Igwenagu E, Igbokwe NA. Aluminium toxicosis: a review of toxic actions and effects. Interdiscip Toxicol. 2019;12:45–70.
He JL, Wu HB, Hu WL, Liu JJ, Zhang Q, Xiao W, et al. Exposure to multiple trace elements and thyroid cancer risk in Chinese adults: a case-control study. Int J Hyg Environ Health. 2022;246:114049.
Gruzewska K, Michno A, Pawelczyk T, Bielarczyk H. Essentiality and toxicity of vanadium supplements in health and pathology. J Physiol Pharm. 2014;65:603–11.
Dąbroś W, Adamczyk A, Ciurkot K, Kordowiak AM. Vanadium compounds affect growth and morphology of human rhabdomyosarcoma cell line. Pol J Pathol. 2011;62:262–8.
Slotnick MJ, Nriagu JO. Validity of human nails as a biomarker of arsenic and selenium exposure: a review. Environ Res. 2006;102:125–39.
Yin X, Yang X, Zhang T, Yuan Z, Chen H, Jin L, et al. Changes of body mass index and body shape in relation to risk of gastric cancer: a population-based case-control study. J Cancer. 2021;12:3089–97.
Yang X, Chen X, Zhuang M, Yuan Z, Nie S, Lu M, et al. Smoking and alcohol drinking in relation to the risk of esophageal squamous cell carcinoma: A population-based case-control study in China. Sci Rep. 2017;7:17249.
Zhang T, Yang X, Yin X, Yuan Z, Chen H, Jin L, et al. Poor oral hygiene behavior is associated with an increased risk of gastric cancer: a population-based case-control study in China. J Periodontol. 2022;93:988–1002.
Janbabai G, Alipour A, Ehteshami S, Borhani SS, Farazmandfar T. Investigation of trace elements in the hair and nail of patients with stomach cancer. Indian J Clin Biochem. 2018;33:450–5.
Lin X, Peng L, Xu X, Chen Y, Zhang Y, Huo X. Connecting gastrointestinal cancer risk to cadmium and lead exposure in the Chaoshan population of Southeast China. Environ Sci Pollut Res Int. 2018;25:17611–9.
Wulaningsih W, Michaelsson K, Garmo H, Hammar N, Jungner I, Walldius G, et al. Serum calcium and risk of gastrointestinal cancer in the Swedish AMORIS study. BMC Public Health. 2013;13:663.
Azin F, Raie RM, Mahmoudi MM. Correlation between the levels of certain carcinogenic and anticarcinogenic trace elements and esophageal cancer in northern Iran. Ecotoxicol Environ Saf. 1998;39:179–84.
Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N. Engl J Med. 2005;352:373–9.
Xie R, Xu J, Xiao Y, Wu J, Wan H, Tang B, et al. Calcium promotes human gastric cancer via a novel coupling of calcium-sensing receptor and TRPV4 Channel. Cancer Res. 2017;77:6499–512.
Prasad AS, Mukhtar H, Beck FW, Adhami VM, Siddiqui IA, Din M, et al. Dietary zinc and prostate cancer in the TRAMP mouse model. J Med Food. 2010;13:70–6.
Dev S, Babitt JL. Overview of iron metabolism in health and disease. Hemodial Int. 2017;21:S6–s20.
Lieu PT, Heiskala M, Peterson PA, Yang Y. The roles of iron in health and disease. Mol Asp Med. 2001;22:1–87.
McCord JM. Effects of positive iron status at a cellular level. Nutr Rev. 1996;54:85–8.
Silbergeld EK. Facilitative mechanisms of lead as a carcinogen. Mutat Res. 2003;533:121–33.
Rinaldi L, Barabino G, Klein JP, Bitounis D, Pourchez J, Forest V, et al. Metals distribution in colorectal biopsies: new insight on the elemental fingerprint of tumour tissue. Dig Liver Dis. 2015;47:602–7.
Bai Y, Feng W, Wang S, Zhang X, Zhang W, He M, et al. Essential metals zinc, selenium, and strontium protect against chromosome damage caused by polycyclic aromatic hydrocarbons exposure. Environ Sci Technol. 2016;50:951–60.
Mark SD, Qiao YL, Dawsey SM, Wu YP, Katki H, Gunter EW, et al. Prospective study of serum selenium levels and incident esophageal and gastric cancers. J Natl Cancer Inst. 2000;92:1753–63.
Steevens J, van den Brandt PA, Goldbohm RA, Schouten LJ. Selenium status and the risk of esophageal and gastric cancer subtypes: the Netherlands cohort study. Gastroenterology 2010;138:1704–13.
Hashemian M, Poustchi H, Abnet CC, Boffetta P, Dawsey SM, Brennan PJ, et al. Dietary intake of minerals and risk of esophageal squamous cell carcinoma: results from the Golestan Cohort Study. Am J Clin Nutr. 2015;102:102–8.
Hashemian M, Murphy G, Etemadi A, Poustchi H, Brockman JD, Kamangar F, et al. Toenail mineral concentration and risk of esophageal squamous cell carcinoma, results from the Golestan Cohort Study. Cancer Med. 2017;6:3052–9.
Overall Evaluations of Carcinogenicity. an updating of IARC Monographs volumes 1 to 42. IARC Monogr Eval Carcinog Risks Hum Suppl. 1987;7:1–440.
Chen Q, Qiu Y, Chen L, Lin J, Yan LJ, Bao XD, et al. Association between serum arsenic and oral cancer risk: a case-control study in southeast China. Community Dent Oral Epidemiol. 2021;50:83–90.
Lee MH, Gao YT, Huang YH, McGee EE, Lam T, Wang B, et al. A metallomic approach to assess associations of serum metal levels with gallstones and gallbladder cancer. Hepatology 2020;71:917–28.
Mannello F, Ligi D, Canale M. Aluminium, carbonyls and cytokines in human nipple aspirate fluids: possible relationship between inflammation, oxidative stress and breast cancer microenvironment. J Inorg Biochem. 2013;128:250–6.
Golasik M, Przybyłowicz A, Woźniak A, Herman M, Gawęcki W, Golusiński W, et al. Essential metals profile of the hair and nails of patients with laryngeal cancer. J Trace Elem Med Biol. 2015;31:67–73.
Qayyum MA, Shah MH. Comparative study of trace elements in blood, scalp hair and nails of prostate cancer patients in relation to healthy donors. Biol Trace Elem Res. 2014;162:46–57.
Qayyum MA, Shah MH. Study of trace metal imbalances in the blood, scalp hair and nails of oral cancer patients from Pakistan. Sci Total Environ. 2017;593-594:191–201.
Khlifi R, Olmedo P, Gil F, Feki-Tounsi M, Chakroun A, Rebai A, et al. Blood nickel and chromium levels in association with smoking and occupational exposure among head and neck cancer patients in Tunisia. Environ Sci Pollut Res Int. 2013;20:8282–94.
Xu J, Zhao M, Pei L, Zhang R, Liu X, Wei L, et al. Oxidative stress and DNA damage in a long-term hexavalent chromium-exposed population in North China: a cross-sectional study. BMJ Open. 2018;8:e021470.
Mirvish SS. Formation of N-nitroso compounds: chemistry, kinetics, and in vivo occurrence. Toxicol Appl Pharm. 1975;31:325–51.
Zhou X, Chen Q, Liu C, Fang Y. Using Moss to Assess Airborne Heavy Metal Pollution in Taizhou, China. Int J Environ Res Public Health. 2017;14:430.
Acknowledgements
We would like to thank the interviewers and technicians of Fudan University Taizhou Institute of Health Sciences for their work in data and sample collection. We also thank the staff of the Taixing Center for Disease Control and Prevention for the help they provided in the study field and the staff of Taixing People’s Hospital for their help in the sample collection.
Funding
This study was supported by the National Natural Science Foundation of China (82173591, 81973116, 82073637, 82204129, 82103912, and 91846302), the National Key Research and Development Program of China (2021YFF1201101, 2017YFC0907003, and 2017YFC0907002), and Shandong Provincial Natural Science Foundation (ZR2022QH162). The funders were not involved in the collection, analysis, or interpretation of data, or the writing or submitting of this report.
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Conceptualization: TZ, QW, LJ, XC, ML, and WY. Data curation, formal analysis, and methodology: TZ, XY, XY, ZY, QW, LJ, XC, ML, and WY. Validation and visualization: TZ, XY, XY. Interpretation: TZ, XY, QW, ML, and WY. Writing original draft: TZ and XY. Review, and/or revision of the draft: QW, LJ, XC, ML, and WY. All authors contributed to and have approved the final manuscript.
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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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This study was approved by the institutional review board of the School of Life Sciences, Fudan University, and the Institutional Review Board of Qilu Hospital, Shandong University. All participants voluntarily joined this study and provided written informed consent.
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Zhang, T., Yin, X., Yang, X. et al. Trace elements in hair or fingernail and gastroesophageal cancers: results from a population-based case-control study. J Expo Sci Environ Epidemiol (2023). https://doi.org/10.1038/s41370-023-00528-y
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DOI: https://doi.org/10.1038/s41370-023-00528-y
Keywords
- Trace element
- Gastroesophageal cancers
- Case-control study
- Risk factor