Amine Chakroun

Arsenic, cadmium, chromium and nickel in cancerous and healthy tissues from patients with head and neck cancer

Chronic exposure to heavy metals has long been recognized as being capable to increase head and neck cancer incidence among exposed human populations. Head and neck cancer is a significant public health issue in Tunisia. The aim of the present study was to evaluate the concentrations of As, Cd, Cr and Ni in healthy and tumor tissues of head and neck cancer patients. Metal concentrations were determined in tumor and healthy tissues of 101 head and neck cancer patients, using Atomic Absorption Spectrometry. The As, Cd, Cr, and Ni levels in tumor tissues were 3.4, 2.5, 1.3 and 1.5 times higher than those of healthy tissues (p<0.05), respectively. Tumor tissue metal levels were higher in men than in women. As and Cd levels in tumor and healthy tissue samples of patients smokers are significantly higher than those of non-smokers (p<0.05). A strong effect of cumulative smoking as expressed in the number of pack per year, and tumor tissue Cd levels were positively associated with three groups of age (<40, 51-60 and >60 years) in both never-smokers and ever-smokers (<20 and ≥20 pack per year). Healthy tissue Cd levels were negatively associated with age in those three groups of smokers. The highest Cd and Cr concentrations among both workers and non-workers were observed in tumor tissues. The Cd and Cr in tissues of farmers, bricklayers and painters were all significantly higher among the workers as compared with the non-workers group. Tissue metal levels have increased due to smoking and occupational exposure. Heavy metal exposure via tobacco smoking and occupational exposures may increase the risk of head and neck in the Tunisian population.

Blood nickel and chromium levels in association with smoking and occupational exposure among head and neck cancer patients in Tunisia.

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 111.60xa0μg/L, respectively) were significantly higher than those of controls (37.04 and 30.50xa0μg/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 (Pu2009<u20090.05). Among these risk factors, smoking and occupational exposure presented the most significant association with HNC (odds ratio (OR)u2009=u20096.54 and 7.66, respectively, Pu2009<u20090.001). 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 (Pu2009<u20090.05). Smokers who are occupationally exposed present the most significant association with HNC (ORu2009=u200925.08, Pu2009<u20090.0001). High levels of blood Cr (ORu2009=u20092.09) and high levels of blood Ni (ORu2009=u20098.87) were strongly associated with HNC after other potential confounders were controlled (Pu2009=u20090.004 and Pu2009<u20090.0001, respectively). This study suggested a potential role of Cr and Ni in the mechanism of HNC development.

Cytogenetic Abnormality in Exfoliated Cells of Buccal Mucosa in Head and Neck Cancer Patients in the Tunisian Population: Impact of Different Exposure Sources

Chromosome/DNA instability could be one of the primary causes of malignant cell transformation. The objective of the present study was to evaluate the spontaneous genetic damages in exfoliated cells of buccal mucosa of head and neck cancer (HNC) by counting micronucleus (MN) and binucleated (BN) cells frequencies. MN and BN frequencies were significantly increased in HNC patients compared with controls (5.53u2009±u20093.09/1000u2009cells, 5.63u2009±u20092.99/1000u2009cells versus 2.36u2009±u20092.11/1000u2009cells, 3.09u2009±u20091.82/1000u2009cells, P < 0.001). Regarding the gender and the age, the frequencies of the MN and BN were significantly higher than those of controls (P < 0.01). The evaluation of the MN and BN frequencies revealed a significant increase (P < 0.001) in the cases in relation to the control group after controlling the risk factors (tobacco smoking and chewing and occupational exposure) of HNC. Moreover, MN and BN frequencies were significantly increased in smokers and chewers compared with nonsmokers and nonchewers among patients (P < 0.05). MN frequency was significantly (P = 0.014) different between patients occupationally exposed (6.99u2009±u20093.40/1000 cells) and nonexposed (4.70u2009±u20092.48/1000u2009cells) among HNC group. The logistic regression model illustrated that HNC was significantly associated with frequencies of MN (ORu2009=u20098.63, P < 0.0001) and BN (ORu2009=u20095.62, P = 0.001). Our results suggest that increased chromosome/DNA instabilities may be associated with HNC.

Association of CYP1A1 and CYP2D6 gene polymorphisms with head and neck cancer in Tunisian patients

The purpose of this study was to investigate the relationship between head and neck cancer (HNC) and environmental agents and polymorphisms in CYP1A1, CYP2D6, NAT1 and NAT2 metabolic enzymes genes. To the best of our knowledge, this is the first report on polymorphisms in CYP1A1 6310C>T, CYP2D6 Arg365His, NAT1 52936A>T and NAT2 Arg268Lys (NAT2*12A) genes and susceptibility to HNC in Tunisian population. We study the prevalence of these polymorphisms in 169 patients with HNC and 261 control subjects using polymerase chain reaction based methods in a Tunisian population. We detected an association between HNC and CYP1A1 6310C>T (TT) and CYP2D6 Arg365His (His/His) variant carriers (OR 1.75, Pxa0=xa00.008 and OR 1.66, Pxa0=xa00.016, respectively). No association was found between the polymorphisms genotypes of NAT1 52936T>A and NAT2 Arg268Lys and risk of HNC. An association between HNC and CYP1A1 (TT) genotype was found among patients with smoking (Pxa0=xa00.011) and drinking habit (Pxa0=xa00.009). The combinations of NAT1 (AT or AA) and NAT2 (AA) at-risk genotypes increased HNC risk (OR 4.23, Pxa0=xa00.005 and OR 3.60, Pxa0=xa00.048, respectively). However, the combinations of CYP1A1 (AA) and CYP2D6 (CC) genotypes decreased risk of HNC (OR 0.20; Pxa0=xa00.006). Genetic polymorphisms in CYP1A1 and CYP2D6 may significantly associate with HNC in the Tunisian population. The results of this study suggest a possible gene–environment interaction for certain carcinogen metabolizing enzymes, but larger studies that fully evaluate the interaction are needed.

Heavy metals in normal mucosa and nasal polyp tissues from Tunisian patients

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 (pu2009<u20090.05), 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 (pu2009=u20090.006, 0.002, and < 0.001, respectively). The highest As concentrations among patients lived at polluted areas (1–25 and > 25xa0years) 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 (pu2009<u20090.05). 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.

Association between blood arsenic levels and nasal polyposis disease risk in the Tunisian population

Although the pathophysiology underlying nasal polyposis (NP) formation is not fully understood, systemic, local, and environmental factors appear to contribute to NP disease development. This study aimed to explore the relationship between metal blood levels and NP risk. To the best of our knowledge, the current research represents the first scientific contribution reporting levels of Cr and As in blood of NP patients. In this context, 90 NP patients and 171 controls were recruited and blood samples were analyzed to determine the concentrations of As and Cr. Metal blood levels of As in patients (2.1xa0μg/L) were significantly higher than those of controls (1.2xa0μg/L). However, no significant difference in blood Cr levels was found between cases and controls. Arsenic blood levels of cigarette smokers were significantly higher than those of non-smokers. Environmental exposure and shisha consumption presented the most significant association with NP disease (ORu2009=u200910.1 and 14.1, respectively). High levels of blood As were significantly associated with NP disease (ORu2009=u20092.1). Cr blood levels were found to be associated with the four stages of polyps in both nasal cavities. This study found a strong association between nasal polyposis disease and As blood levels. These findings merit further investigation.

Inter-ethnic differences in genetic polymorphisms of xenobiotic-metabolizing enzymes (CYP1A1, CYP2D6, NAT1 and NAT2) in healthy populations: correlation with the functional in silico prediction

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.