Relationships Between Biological Heavy Metals and Breast Cancer: A Systematic Review and Meta-Analysis

Abstract

IntroductionHeavy metals were classified as essential, probably essential, and potentially toxic in the general population. Until now, it has been reported inconsistently on the association between heavy metals and BC. In this meta-analysis, we aimed to assess the association between heavy metals and BC and review the potential mechanisms systematically.MethodsWe searched for epidemiological studies in English about the association between heavy metals and BC published before September 2020 in PubMed, Web of Science, and Embase databases. In total 36 studies, comprising 4,151 individuals from five continents around the world were identified and included.ResultsIn all biological specimens, Cu, Cd, and Pb concentrations were higher, but Zn and Mn concentrations were lower in patients with BC than in non-BC participants [SMD (95% CIs): 0.62 (0.12, 1.12); 1.64 (0.76, 2.52); 2.03 (0.11, 3.95); −1.40 (−1.96, −0.85); −2.26 (−3.39, −1.13); p = 0.01, 0.0003, 0.04, <0.0001, <0.0001]. Specifically, higher plasma or serum Cu and Cd, as well as lower Zn and Mn, were found in cases [SMD (95% CIs): 0.98 (0.36, 1.60); 2.55 (1.16, 3.94); −1.53 (−2.28, −0.78); −2.40 (−3.69, −1.10); p = 0.002, 0.0003, <0.0001, 0.0003]; in hair, only lower Zn was observed [SMD (95% CIs): −2.12 (−3.55, −0.68); p = 0.0004]. Furthermore, the status of trace elements probably needs to be re-explored, particularly in BC. More prospective studies, randomized clinical trials, and specific pathogenic studies are needed to prevent BC. The main mechanisms underlying above-mentioned findings are comprehensively reviewed.ConclusionFor BC, this review identified the current knowledge gaps which we currently have in understanding the impact of different heavy metals on BC.Systematic Review Registrationwww.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020176934, identifier: CRD42020176934.

Impact of heavy metals on breast cancer (Review)

“…In subgroup analyses by region, significantly higher copper concentrations in plasma and serum have been observed in breast cancer patients from Africa and Europe compared to participants without breast cancer. By contrast, no statistically significant changes have been observed between Asian patients with breast cancer and subjects without cancer (100). The copper levels in patients with breast cancer have been well-presented in the literature and a summary of these findings is presented in Table III (50)(51)(52)93,94,96,97,(101)(102)(103)(104)(105).…”

“…The urinary concentrations of cadmium have been shown to be considerably elevated in individuals diagnosed with breast cancer compared to the controls, as determined by the utilization of inductively coupled plasma techniques (107,108). Studies using atomic absorption and atomic emission spectroscopy have reported mixed results, with some demonstrating higher cadmium concentrations in patients with breast cancer and others finding no significant differences (100,109,110). Other studies have determined the evaluation of cadmium in sample tissue using different techniques, including atomic absorption spectroscopy, graphite furnaces and inductively coupled plasma.…”

“…The diminishment of manganese levels can disrupt the body's ability to counteract oxidative stress, thereby elevating the vulnerability of target organs to carcinogenic agents. As shown in Table VI, several investigations have compared manganese concentrations in patients with breast cancer and participants without breast cancer (97,100,(137)(138)(139). Studies investigating manganese levels in patients with breast cancer have found lower concentrations of manganese in the plasma, serum and hair samples of patients with breast cancer compared to participants without breast cancer in Asia (100,137).…”

“…As shown in Table VI, several investigations have compared manganese concentrations in patients with breast cancer and participants without breast cancer (97,100,(137)(138)(139). Studies investigating manganese levels in patients with breast cancer have found lower concentrations of manganese in the plasma, serum and hair samples of patients with breast cancer compared to participants without breast cancer in Asia (100,137). However, the differences were not statistically significant in Europe (100).…”

“…Studies investigating manganese levels in patients with breast cancer have found lower concentrations of manganese in the plasma, serum and hair samples of patients with breast cancer compared to participants without breast cancer in Asia (100,137). However, the differences were not statistically significant in Europe (100). It is important to underscore that manganese, in its role as a contributor to antioxidant defense, may influence the ability of the body to manage oxidative stress and may affect the delicate equilibrium between oxidants and antioxidants in patients with breast cancer from a theoretical perspective (140,141).…”