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ORIGINAL ARTICLE
Year : 2018  |  Volume : 67  |  Issue : 1  |  Page : 56-61

Heavy metals assessment in Egyptian smokers with lung cancer


1 Department of Chest, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Date of Submission05-Nov-2017
Date of Acceptance31-Dec-2017
Date of Web Publication21-Mar-2018

Correspondence Address:
Taha T Abdelgawad
Chest Department, Faculty of Medicine, Mansoura University, Mansoura 35516
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejcdt.ejcdt_10_17

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  Abstract 

Background Smoking and heavy metals are major risk factors and have an important role in development of lung cancer.
Purpose The purpose of this study was to investigate the relationship between development of lung cancer and the synergistic effect of smoking and heavy metals in Egyptian smokers.
Patients and methods A total of 41 participants enrolled in this study and were subdivided into three groups: smokers with lung cancer (n=11), nonsmokers with lung cancer (n=15), and apparently healthy smokers (n=15). The diagnosis and types of lung cancer based on pathological examination of biopsies taken either by computed tomography-guided, ultrasound-guided, fiberoptic bronchoscopy (FOB), and blind or thoracoscopic pleural biopsy. Serum levels of five heavy metals (zinc, lead, nickel, manganese, chromium) were assayed using inductive plasma spectrometry.
Results Squamous cell carcinoma represents the major type of lung cancer (72.7%) among group of smokers with lung cancer; however, adenocarcinoma either primary or metastatic represents the major type (93.4%) among the nonsmoker group, and all investigated heavy metals in this study (zinc, lead, nickel, manganese, chromium) express significantly higher mean value of their serum levels (P=0.005, 0.005, 0.006, <0.001, and 0.007, respectively) in case of squamous cell carcinoma compared with adenocarcinoma. There is no impact of the degree of severity of smoking on serum levels of all investigated heavy metals.
Conclusion Squamous cell carcinoma has been strongly associated with higher serum levels of all investigated heavy metals. There is no association between degree of severity of smoking and serum levels of all investigated heavy metals.

Keywords: heavy metals, inductive plasma spectrometry, lung cancer, smoking


How to cite this article:
Abdelgawad TT, El-Maboud Suliman LA, Nabil Helaly AM, Motawei SM, Abdelghany DA. Heavy metals assessment in Egyptian smokers with lung cancer. Egypt J Chest Dis Tuberc 2018;67:56-61

How to cite this URL:
Abdelgawad TT, El-Maboud Suliman LA, Nabil Helaly AM, Motawei SM, Abdelghany DA. Heavy metals assessment in Egyptian smokers with lung cancer. Egypt J Chest Dis Tuberc [serial online] 2018 [cited 2020 Apr 3];67:56-61. Available from: http://www.ejcdt.eg.net/text.asp?2018/67/1/56/228127


  Introduction Top


According to the American Cancer Society, the estimated new cancers in USA in 2017 were 836 150 in males (14% were lung and bronchus) and 852 650 in females (12% were lung and bronchus), and the estimated cancer deaths were 328 420 in males (27% owing to lung and bronchus) and 282 500 in females (25% owing to lung and bronchus) [1]. In Egypt, bronchial carcinoma represents 8.2% of Egyptian cancer in males and the study expected a three-fold increase in cancer rates by 2050 [2]. For normal metabolism, the human body needs elements such as Zn, Mg, Mn, Cr, Ni, Mo, Co, Fe, Cu, K, Ca, Na, and Sn; however, the concentrations of these elements that can cause toxicity depends on the different lifestyles of the individuals [3].

A recent study conducted in Shanghai revealed that the air pollution with lead-containing dust may be linked to lung cancer in both sexes in this overcrowded city [4].

In addition, a significant dose–response relationship had been found between the soil concentration of several heavy metals (including As, Cd, Hg, and Pb) and the rise of different types of lung cancer such as nonsmall cell lung cancer and small cell lung cancer [5].

Trace amounts of metals that are present in tobacco smoke has been known for some time [6]. Cadmium (Cd), chromium (Cr), nickel (Ni), arsenic (As), and lead (Pb), as well as Ni compounds, were the most commonly associated with health effects, and they are all designated as carcinogenic to human body by the International Agency for Research on Cancer [7].

In addition, it was reported that excessive smoking may lead to high uptake of toxic heavy metals in lung tissue and stimulate the growth of lung cancer [8]. The analysis of trace heavy metals in human tissues has acquired lustrous interest owing to the fact that these elements play a role − through biochemical in addition to physiological processes − in the development and/or progression of some cancers [9],[10].

This work is aimed to investigate the relationship between lung cancer development and the synergistic effect of smoking and heavy metals in Egyptian smokers.


  Patients and methods Top


This prospective study was conducted on 41 participants recruited from Chest Medicine Department, Mansoura University Hospital. Twenty-six lung cancer patients and 15 control apparently healthy smokers from smoking outpatient clinic in the period from October 2014 to August 2016 were included in this study. All of them were above 18 years old and consent was taken from all participants. All procedures done involving human participants were in accordance with the ethical standards of the Mansoura University.

The participants enrolled in this study were subdivided into three groups:
  1. Nonsmokers with lung cancer: 15 patients.
  2. Smokers with lung cancer: 11 patients.
  3. Apparently healthy smokers (control group): 15 participants.


All of them underwent the following:
  1. History taking and clinical examination with stress on smoking index calculation, general examination and local chest examination, chest radiography and computed tomography of chest for detection of the site of the lesion, and to choose the most appropriate interventional biopsy for pathological examination: fiberoptic bronchoscopy (FOB) for 12 patients for centrally located lesion or lung collapse, computed tomography-guided biopsy for four patients of peripherally situated lesion, ultrasound-guided biopsy for two patients, blind pleural biopsy for five patients, and thoracoscopic biopsy for three patients presented with pleural effusion. All biopsies were sent for pathological examination for detection of lung cancer types.
  2. Blood sampling was taken from patients and control for assessment of levels of different heavy metals in toxicology lab of Forensic and Toxicology Department, Mansoura University, and frozen at −80°C. For further analysis, concentration curve was extrapolated from serial dilutions from a stock solution containing 1000 mg/l of lead, nickel, chromium, manganese, and zinc with concentrations of 0.5, 1, 1.5, 2, 2.5, 3, 3.5, and 4 mg/l using deionized water. Later on, these controls have been assayed using inductive plasma spectrometer (Perkin Elmer Model: Optima 7000 DV; PerkinElmer, Rodgau, Germany) to build up the standard curve. The different sample concentrations were blotted to the curve. This curve was used to measure the sample concentration by WinLab32 Software (PerkinElmer, Rodgau, Germany).


Normal ranges of heavy metals:
  1. Chromium 0.8–5.1 µg/l.
  2. Manganese 4–15 µg/l.
  3. Nickel 0.01–0.042 µg/l in smokers and 0.01–0.26 µg/l in nonsmokers.
  4. Lead 0.5 µg/l.
  5. Zinc 6–7.2 µg/l.


The references for trace elements are in micrograms per liter; the results of our study are in micrograms per liter, which is 1000 times micrograms.

Statistical analysis

The collected data were coded, processed, and analyzed using the statistical package for the social sciences version 15 for Windows (SPSS; SPSS Inc., Chicago, Illinois, USA). Qualitative data were presented as number and percentage and χ2-test was used to compare between groups. Quantitative data were presented as mean±SD, and to compare between two groups Student’s t-test was used. Nonparametric data were presented as minimum–maximum and median. Mann–Whitney test was used for comparison between groups. Comparison between more than two groups was done by Kruskal–Wallis test. P value less than 0.05 was considered to be statistically significant.


  Results Top


The study was conducted on 41 participants with a mean age of 45.63+15.46 years. [Table 1] demonstrates the demographic data of the enrolled individuals: 22 (53.7%) were male and 19 (46.3%) were female, and 13 (31.7%) were farmers and 28 (68.3%) were nonfarmers. The degree of smoking severity according to smoking index was mild (n=9), moderate (n=11), and severe (n=6). Squamous cell carcinoma represents the major type of lung cancer (72.7%) among group of smokers with lung cancer; however, adenocarcinoma either primary or metastatic represents the major type (93.4%) of lung cancer among the group of nonsmokers with lung cancer.
Table 1 Demographic characteristics of all studied individuals

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[Table 2] showed significantly higher mean value of serum levels of zinc and manganese (P<0.001 and 0.039, respectively) in smokers with lung cancer compared with the nonsmokers with lung cancer group; however, the reverse was found as regards nickel (P=0.012). No significant difference was detected between both groups in case of lead and chromium.
Table 2 Serum levels of heavy metals in smokers with lung cancer versus nonsmokers with lung cancer

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[Table 3] showed significantly higher mean value of serum zinc level (P<0.001) in smokers with lung cancer compared with apparently healthy smokers group; however, the reverse was found as regards nickel (P=0.020). Despite the higher mean value of serum levels of lead, manganese, and chromium in smokers with lung cancer compared with apparently healthy smokers group, it is not statistically significant.
Table 3 Serum levels of heavy metals in smokers with lung cancer versus apparently healthy smokers (control group)

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[Table 4] showed significantly higher mean value of serum level of lead (P=0.002) in nonsmokers with lung cancer compared with apparently healthy smokers group; also, the mean value of serum level of nickel was higher in nonsmokers with lung cancer compared with apparently healthy smokers group but not statistically significant, despite the higher mean value of serum levels of zinc, manganese, and chromium in apparently healthy smokers.
Table 4 Serum levels of heavy metals in nonsmokers with lung cancer versus apparently healthy smokers (control group)

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[Table 5] demonstrates that all investigated heavy metals in this study (zinc, lead, nickel, manganese, and chromium) express significantly higher mean value of their serum levels (P=0.005, 0.005, 0.006, <0.001, and 0.007, respectively) in case of squamous cell carcinoma type compared with adenocarcinoma. There were no statistically significant differences in studied heavy metals in relation to smoking index severity groups (mild, moderate, and severe), as shown in [Table 6].
Table 5 Serum levels of heavy metals in relation to pathological types of lung cancer

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Table 6 Serum levels of heavy metals in relation to severity of smoking

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  Discussion Top


The current study discusses a sample of lung cancer pattern in relation to toxicological risk factors, and we aimed to investigate the relationship between lung cancer development and the synergistic effect of smoking and heavy metals in Egyptian smokers.

The mean age of enrolled participants in this study was 45.63+15.46 years, and 22 were male and 19 were female. Squamous cell carcinoma was present in 72.7% of the smokers with lung cancer group; however, adenocarcinoma and its subtypes were present in 93.4% in the nonsmoker group. The study assayed five heavy metals (zinc, lead, nickel, manganese, and chromium). All participants tested in the study expressed high serum heavy metals levels than international accepted levels of zinc, lead, nickel, manganese, and chromium. Furthermore, zinc was eight-fold higher in smokers with lung cancer in contrast to apparently healthy control smokers.

In the current study, we found that zinc and manganese were significantly higher in smokers with lung cancer compared with nonsmokers; however, in case of the smokers with lung cancer group versus apparently healthy smokers group, zinc is the only heavy metal that was statistically elevated in the first group. This result was supported by multiple researches who documented that cumulative smoking is directly correlated with exposure to heavy metals, which may predispose smokers to increased risk of developing head and neck cancer in a Tunisian population study [11],[12].

Moreover, an ecological study was conducted by Spangler and Reid [13] for evaluation of potential carcinogenic effects of Mn, and they found that groundwater, smoking, or air concentrations of Mn are correlated with an increase in cancer rates at all sites including colon cell carcinoma.

Some studies demonstrate the role of zinc either in development or regression of cancer as in animal studies that reported that zinc administration may slow the progression of induced tumors. Other studies in humans found that zinc administration and other micronutrients may have therapeutic effects in patients with precancerous lesions in the mouth cavity [14]. However, high serum zinc level was detected in cancer liver and in colon cancer patients [15]. Thus, zinc may play a diverse role in various types of cancers.

Nonsmokers with lung cancer group showed statistically significant elevation in serum level of nickel versus smokers with lung cancer group (P=0.012); this was in accordance with Huang et al. [5], who found that adenocarcinoma was related to high nickel and copper. It is important that the study made that association with the level of different metals in the soil but did not examine the levels of different heavy metals in the blood of the patients as direct association [5].

Therefore, we have other sources of heavy metals apart from smoking, mostly the intoxicated soil. The food chain supplies the population with high level of heavy metals. It is noteworthy that industry is another source for heavy metals that affects both rural and urban areas.

In the present work, serum lead level was significantly elevated in nonsmokers with lung cancer group versus apparently healthy smokers (P=0.002); similar results were found in Taiwan study where high lead level was related to adenocarcinoma [5]. The assays in soil and patients bloods are two sides of one coin.

Researchers from Taiwan concluded that heavy metals such as chromium, copper, mercury, nickel, and zinc were associated with squamous cell type of lung cancer [5]. This conclusion was in agreement with our results that reported high serum level of heavy metals (Zn, lead, Mn, nickel, and Cr) in squamous cell lung cancer group. Zinc was seven-fold higher in squamous cell type and manganese was eight-fold higher also.

It is possible to say that combined smoking and heavy metal toxicity plays a role in the pathogenesis of squamous cell carcinoma of the lung as it was the major type in smokers in the lung cancer group and also associated with significantly higher serum level of the all investigated heavy metals in our study; this may be explained by the state of oxidative stress created by both smoking and heavy metal toxicity.

Severity of smoking index did not have a significant impact on serum level of all investigated heavy metals in the current study; however, other studies reported that the exposure level to heavy metals in the smoke from a single cigarette does not cause acute toxicity such as accumulation of toxic heavy metals in the human body for long period as months or years of smoking, depending on rates of clearance and health concern [16],[17]. This difference in results could be due to other risk factors associated with smoking in elevation of toxic heavy metals in the current study.


  Conclusion Top


On the basis of the results of the present study, we can conclude that combined heavy metal toxicity and smoking are challenging risk factors that may play a crucial role in the pathogenesis of lung cancer. Squamous cell carcinoma that represents the major type of lung cancer in smokers also has been strongly associated with significant higher serum levels of all investigated heavy metals (Zn, Pb, Mn, Ni, and Cr). There is no association between degree of severity of smoking and serum levels of all investigated heavy metals. Further study on a large scale is needed to confirm and to further elucidate the relationship between heavy metal toxicity and development of some types of lung cancers specifically in smokers.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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