Sfax, Tunisia
Sfax, Tunisia

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Khlifi R.,University of Sfax | Khlifi R.,Bioinformatics Unit | Olmedo P.,University of Granada | Gil F.,University of Granada | And 5 more authors.
Environmental Monitoring and Assessment | Year: 2014

The human health impact of the historic and current mining and industrial activities in Tunisia is not known. This study assessed the exposure to metals in the population of Southern Tunisia, using biomonitoring. The aim of this pilot study was to evaluate metal exposure on 350 participants living near mining and active industrial areas in the South of Tunisia. Blood specimens were analyzed for metals (Cd, Cr, As, and Ni) by Atomic Absorption Spectrometer equipped with Zeeman background correction and AS-800 auto sampler by graphite furnace and graphite tubes with integrated L'vov platform. The sample population was classified according to different age groups, sex, smoking habit, sea food and water drinking consumption, occupational exposure, amalgam fillings and place of residence. The blood As, Cd, Cr and Ni values expressed as mean ± SD were 1.56 ± 2.49, 0.74 ± 1.15, 35.04 ± 26.02 and 30.56 ± 29.96 μg/l, respectively. Blood Cd and Ni levels in smokers were 2 and 1.2 times, respectively, higher than in non-smokers. Blood Cd levels increase significantly with age (p = 0.002). As, Cd and Ni were significantly correlated with gender and age (p < 0.05). Cd level in blood samples of subjects occupationally exposed was 1.3 times higher than that of non-exposed. Blood metals were not significantly affected by amalgam fillings, place of living and sea food and drinking water consumption. This first biomonitoring study of metal exposure in the South of Tunisia reveals a substantial exposure to several metals. The pathways of exposure and health significance of these findings need to be further investigated. © 2013 Springer Science+Business Media Dordrecht.


Khlifi R.,University of Sfax | Khlifi R.,Bioinformatics Unit | Olmedo P.,University of Granada | Gil F.,University of Granada | And 5 more authors.
Environmental Science and Pollution Research | Year: 2014

Chronic exposure to heavy metals has long been recognized as being capable of increasing head and neck cancer (HNC) incidence, such as laryngeal (LC) and nasopharyngeal (NPC), among exposed human populations. The aim of the present study was to evaluate the concentrations of arsenic (As) and cadmium (Cd) in the blood of 145 patients (LC and NPC) and 351 controls in order to establish a potential relationship between these factors and the occurrence of LC and NPC. Mean blood levels of As and Cd in patients (5.67 and 3.51 μg/L, respectively) were significantly higher than those of controls (1.57 and 0.74 μg/L, respectively). The blood levels of As and Cd were mostly significantly higher than those of controls (p < 0.05) after controlling the other risk factors of HNC including tobacco smoking and chewing, and alcohol drinking. Cd levels in blood increase significantly with the number of occupational exposure years for patients (p < 0.05). However, seafood was not found to be contributing as an exposure source. Among these risk factors, smoking (>30 pack years) and occupational exposure (>20 years) presented the most significant association with HNC (OR = 10.22 and 10.38, respectively, p < 0.001). Cd level in blood sample of cases that are occupationally exposed/tobacco users (smokers and chewers) were higher than that of non-occupationally exposed/nontobacco users (p < 0.001). The logistic regression model illustrated that HNC (LC + NPC) was significantly associated with blood levels of As (OR = 2.41, p < 0.001) and Cd (OR = 4.95, p < 0.001). © 2013 Springer-Verlag Berlin Heidelberg.


Khlifi R.,University of Sfax | Khlifi R.,Bioinformatics Unit | Olmedo P.,University of Granada | Gil F.,University of Granada | And 2 more authors.
Environmental Science and Pollution Research | Year: 2015

Nasosinusal polyposis (NSP) is a chronic inflammatory disease of the nasal mucosa. Although the pathophysiology underlying NSP formation is not fully understood, environmental factors appear to be contributed the development of this disease. A case–control study of Tunisian patients was examined to assess the levels of cadmium (Cd) and nickel (Ni) in blood and reparse the association between the exposure to these metals and the risk of nasosinusal polyposis disease. Mean blood levels of Cd in patients (2.2 ± 12.8 μg/L) were significantly higher than those of controls (0.5 ± 0.7 μg/L). Levels of blood Cd were positively correlated with tobacco smoking and chewing among controls. The Cd and Ni concentrations among control (p = 0.001) and patient (p = 0.018) tobacco consumers (smoking, chewing, and shisha) were significantly higher than those nonconsumers. Additionally, Ni blood levels of patient and control smokers were significantly higher than those of nonsmokers. Cd levels in blood samples of NSP patients occupationally exposed for more than 14 years were eight times higher than that of nonexposed. Drinking water was also found to be incriminated as exposure sources. Among risk factors, shisha consumption, environmental exposure, and occupational exposure presented the most significant association with NSP disease (odds ratio (OR) = 14.1, 10.1, and 1.7, respectively). High levels of blood Cd (OR = 3.5) were strongly associated with NSP disease (p = 0.027). Ni blood levels were shown to be associated with the four stages of polyps in both nasal cavities (right and left) (p < 0.05). This investigation suggested a potential role of toxic metals in the mechanism of NSP disease development. Exposure assessment investigations encompassing a wider population are needed. © 2014, Springer-Verlag Berlin Heidelberg.


Khlifi R.,University of Sfax | Khlifi R.,Bioinformatics Unit | Olmedo P.,University of Granada | Gil F.,University of Granada | And 3 more authors.
Environmental Science and Pollution Research | Year: 2014

Despite growing evidence that bacteria, fungi, allergens, and superantigens play a prominent role in the pathophysiology of nasal polyps (NP), the exact cause of polyposis is still unknown. The etiology of NP is considered multifactorial. Until now, there is no information on the presence of heavy metals, such as cadmium (Cd), chromium (Cr), nickel (Ni), and arsenic (As) or of their role, in the pathogenesis of NP disease. In this study, concentrations of these four metals in tissue of NP were determined using Atomic Absorption Spectrometry. The Ni, Cr, and As levels in NP tissues were 2.1-, 3.2-, and 8.0-fold higher than those of normal mucosa (p < 0.05), respectively. A strong effect of cumulative smoking as expressed in the number of pack per year (PY), Ni, As, and Cd levels in NP tissue samples of patients ever-smokers (1-20 and >20 PY) are significantly higher than those of non-smokers (p = 0.006, 0.002, and < 0.001, respectively). The highest As concentrations among patients lived at polluted areas (1-25 and > 25 years) were observed in both nasal mucosa and NP tissues. The Ni and As in both nasal mucosa and NP tissues of patients occupationally exposed were significantly higher than non-exposed group. Cr and As levels were found to be associated with NP stage classification (p < 0.05). This is the first report to describe an association between concentrations of metals (Cr, As, and Ni) in human NP tissues and the risk of NP disease. Tissue metal levels have increased due to smoking, environmental, and occupational exposure. Therefore, heavy metal exposure may increase the risk of NP in the Tunisian population. The considerable risk in the category of highest cumulative exposure argues for an association between heavy metals exposure and nasal polyposis risk. Future investigations with larger samples should better elucidate this association. © 2014 Springer-Verlag Berlin Heidelberg.


Khlifi R.,University of Sfax | Khlifi R.,Bioinformatics Unit | Kallel I.,Bioinformatics Unit | Hammami B.,Habib Borguiba Hospital | And 2 more authors.
Journal of Oral Pathology and Medicine | Year: 2014

Altered activity of DNA repair enzymes may be involved in modulating cancer susceptibility and pathogenesis of head and neck cancer (HNC). We conducted a case-control study to test the association between three common single-nucleotide polymorphisms of XRCC1, ERCC2, and ERCC3 genes with HNC risk in Tunisian patients. To the best of our knowle dge, this is the first report on polymorphisms in XRCC1, ERCC2, and ERCC3 and susceptibility to HNC in our population. The genotype analyses of XRCC1 Arg399Gln, ERCC2 Lys751Gln, and ERCC3 7122 A>G polymorphisms for 169 HNC patients, and 261 controls were performed using the PCR-based restriction fragment length polymorphism. Stratification of the populations according to smoking and drinking habits and occupational exposure highlighted the importance of tobacco, alcohol, and toxic substance as three risk co-factors for the development of HNC. Our study suggests that only the XRCC1 Arg399Gln polymorphism was associated with the risk of HNC in the Tunisian population (OR = 2.04; P = 0.001). Furthermore, the risk of HNC was associated with XRCC1 Arg399Gln polymorphism stratified by occupational exposure status (OR = 2.29; P = 0.024). However, no statistically significant association was observed between the risk of developing HNC and the ERCC2 Lys751Gln and ERCC3 A>G polymorphisms. These data suggest that the XRCC1 Arg399Gln polymorphism is associated with an increased risk of developing HNC, because it correlates with occupational exposure in Tunisian population. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Khlifi R.,University of Sfax | Khlifi R.,Bioinformatics Unit | Olmedo P.,University of Granada | Gil F.,University of Granada | And 5 more authors.
Environmental Science and Pollution Research | Year: 2013

Chronic exposure to chromium (Cr) and nickel (Ni) has long been recognized as being capable to increase head and neck cancer (HNC) incidence among exposed human populations. This study represents the first biomonitoring of Cr and Ni exposure in Tunisia and focuses on a possible association with HNC risk. The aim of the present study was to evaluate the concentrations of Cr and Ni in the blood of HNC patients and controls. Metals blood levels of 169 HNC patients and 351 controls were determined using a Perkin-Elmer Analyst 800 Atomic Absorption Spectrometer. Mean blood levels of Cr and Ni in HNC cases (52.15 and 111.60 μg/L, respectively) were significantly higher than those of controls (37.04 and 30.50 μg/L, respectively). Cases' blood levels of Cr and Ni were significantly higher than those of controls after controlling for the other risk factors of HNC, including smoking, shisha consumption, occupational exposure, and nearby environment (P < 0.05). Among these risk factors, smoking and occupational exposure presented the most significant association with HNC (odds ratio (OR) = 6.54 and 7.66, respectively, P < 0.001). Cr and Ni levels in blood sample of cases and controls that are smoker/occupationally exposed were higher than that of non-smoker/non-occupationally exposed (P < 0.05). Smokers who are occupationally exposed present the most significant association with HNC (OR = 25.08, P < 0.0001). High levels of blood Cr (OR = 2.09) and high levels of blood Ni (OR = 8.87) were strongly associated with HNC after other potential confounders were controlled (P = 0.004 and P < 0.0001, respectively). This study suggested a potential role of Cr and Ni in the mechanism of HNC development. © 2013 Springer-Verlag Berlin Heidelberg.


Khlifi R.,University of Sfax | Khlifi R.,Bioinformatics Unit | Ben Salah G.,University of Sfax | Chakroun A.,Habib Borguiba Hospital | And 2 more authors.
Molecular Biology Reports | Year: 2014

Several studies have shown that many polymorphisms of the xenobiotic-metabolizing enzymes (XME) affect either enzymatic functions or are associated with various aspects of human health. Owing to the presence of these single nucleotide variants (SNVs), differences in detoxification capacity have been observed between many ethnicities. The aim of this investigation was to study the prevalence of four polymorphisms in XME among various ethnic groups. Attention was focused on polymorphisms of CYP2D6 (rs1058172, G>A, p.Arg365His), CYP1A1 (rs4646421, c.-26-728C>T), NAT1 (rs4921880, c.-85-1014T>A) and NAT2 (rs1208, A>G, p.Arg268Lys). These polymorphisms were analyzed in 261 healthy Tunisians individuals in comparison with different ethnic backgrounds from hapmap database. In addition, in silico functional prediction was also performed to determine the loss of function variants. Our results demonstrated that population's origins widely affect the genetic variability of XME enzymes and Tunisians show a characteristic pattern. In silico predictions showed a deleterious effect for p.Arg268Lys substitution on CYP2D6 function, findings confirmed its key role played in cancer susceptibility. These data show that detoxification genes structures depend on the studied population. This suggests that ethnic differences impact on disease risk or response to drugs and therefore should be taken into consideration in genetic association studies focusing on XME enzymes. Our results provide the first report on these SNV in Tunisian population and could be useful for further epidemiological investigations including targeted therapy. © 2014 Springer Science+Business Media.

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