Imen Kallel

Genetic Polymorphisms in the EGFR (R521K) and Estrogen Receptor (T594T) Genes, EGFR and ErbB-2 Protein Expression, and Breast Cancer Risk in Tunisia

We evaluated the association of epidermal growth factor receptor (EGFR) 142285G>A (R521K) and estrogen receptor alpha (ESR1) 2014G>A (T594T) single nucleotide polymorphisms with breast cancer risk and prognosis in Tunisian patients. EGFR 142285G>A and ESR1 2014G>A were genotyped in a sample of 148 Tunisian breast cancer patients and 303 controls using PCR-RFLP method. Immunohistochemitsry was used to evaluate the expression levels of EGFR, HER2, ESR1, progesterone receptor and BCL2 in tumors. We found no evidence for an association between EGFR R521K polymorphism and breast cancer risk. However, we found that the homozygous GG (Arg) genotype was more prevalent in patients with lymph node metastasis (P = .03) and high grade tumors (P = .011). The ESR1 2014G allele showed significant association with breast cancer risk (P = .025). The GG genotype was associated with HER2 overexpression and this association withstood univariate and multivariate analyses (P = .009; P = .021, resp.). These data suggest that the R521K might be a prognostic factor, because it correlates with both tumor grade and nodule status. The higher expression of HER2 in ESR1 T594T GG patients suggests the possibility that ESR1 gene polymorphisms accompanied by HER2 expression might influence the pathogenesis of breast cancers.

Association of polymorphisms in estrogen and thyroid hormone receptors with thyroid cancer risk

The receptors for thyroid hormone (THR) and oestrogen (ESR) are prototypes of nuclear transcription factors that regulate the expression of target genes. Genetic alterations in the genes of these receptors were found to be involved in cancer development. In this study we investigated the association of one SNP (rs2228480, T594T) and one microsatellite marker (D6S440) within the ESR1 gene and a dinucleotide repeat (D17S2189) within the THRA gene, with thyroid cancer risk. A case-control association study was conducted with 299 healthy individuals and 106 patients with thyroid cancer. Genotypic and allelic frequencies for the dinucleotide repeat in the ESR1 gene were similar between thyroid cancer patients and controls. For the AC repeat in the THRA gene, a slightly significant difference was found for the genotype 18/20 between the two groups (P = 0.034), which suggests that alleles with less than 20 repeats might have a protective effect in thyroid cancer risk. For the SNP T594T, the A allele was much more prevalent in patients than in controls and was highly associated with the risk of thyroid cancer (OR: 4,56; IC: 3.23–6.44; P < 10−18) and seems to have an additive mode of action. In conclusion, our data suggest that the SNP T594T but not the D6S440 and D17S189 is associated with thyroid cancer risk.

HER2 Polymorphisms and Breast Cancer in Tunisian Women

HER2 has been thought to play a critical role in both breast cancer development and progression. Any functional polymorphisms can potentially affect breast cancer risk as well as cancer phenotype and outcome. In our study, we analyzed three polymorphisms in the HER2 gene: the single-nucleotide polymorphism (SNP) HER2 Ile(655)Val as well as another SNP (rs903506) close to it and a new screened dinucleotide repeat H(AC)I4 in intron 4, in a sample of 148 cases and 290 controls from the Tunisian population and investigated their association with breast cancer risk. For the HER2 Ile(655)Val, we found similar allele frequencies between cases and controls (frequency of I allele was 0.92 and 0.91, respectively). The same was observed for the noncoding SNP (rs903506). These two SNPs also showed no association with any clinical parameters, except the association of HER2 Ile(655)Val with tumor size (p = 0.002). But, a significant association was found between the short tandem repeat (STR) [H(AC)I4] and breast cancer risk at both genotypic and allelic levels (p = 0.0004 and p = 0.0001, respectively). Multivariate analysis with binary logistic regression of disease status on genotypes of the three polymorphisms confirmed the association of STR with breast cancer risk (p = 0.016). Therefore, this STR seems to be a promising biomarker in breast cancer and deserves further investigation.

New electronic cane for visually impaired people for obstacle detection and recognition

In this paper, we describe a new electronic white cane for visually impaired people. Our device may enable blind individuals to see the world with their ears. In fact, we used different types of sensors to detect and recognize obstacles. Our choice of sensors is based not only on system requirement but also on technology cost. Accordingly, we used two ultrasonic sensors and one monocular camera. With such low-cost measurement units, we rely on fusing data obtained by our complementary sensors in further steps. An alert speech message is then sent to the user making him know about the presence and nature of potential encountered obstacle by means of a Bluetooth module.

DNA repair gene polymorphisms and risk of head and neck cancer in the Tunisian population.

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.

EGFR overexpression relates to triple negative profile and poor prognosis in breast cancer patients in Tunisia

Background: The prognosis of breast carcinoma is related to a large variety of clinical and pathological factors. Currently, only oestrogen (ER) and progesterone (PR) receptors and human epidermal growth factor receptor 2 (HER2) are used in routine pathological assessment as biomarkers. The aim of this study was to evaluate the prognostic impact of epidermal growth factor receptor (EGFR) expression individually and in combination to classical biomarkers (HER2, ER, and PR), and its relation to tumors with triple negative profile in Tunisian breast carcinoma. Methods: Immunohistochemistry was used to estimate the rate expression of these receptors. Univariate and multivariate analyses were used to explore the prognostic significance of EGFR in this study. Results: The expression rate of EGFR was 28.6%. EGFR expression was inversely correlated to that of ER (P < 0.001). Significant correlations between the expression of EGFR and the high histological Scarff-Bloom-Richardson (SBR) grade (P = 0.038) and also with tumors size (P = 0.041) were observed. The triple negative profile (TN: ER−/PR−/HER2−) was present in 17.3% of cases. EGFR overexpression was positively associated with this clinical aggressive profile (P < 0.001). Survival analysis showed that EGFR expression was associated with poor survival of patients (P = 0.004). In multivariate analysis, EGFR expression (P = 0.035) was found to be independent prognostic factors (significantly correlated to survival). Conclusion: EGFR overexpression was observed in 28.6% of Tunisian breast carcinoma, associated with unfavorable prognosis and with triple negative tumors. Systemically evaluation of EGFR in breast carcinoma could benefit especially to TN subgroup from EGFR targeting agents.

Mutations and polymorphisms of estrogens receptors genes and diseases susceptibility

Background: Estrogen receptors (ER) belong to the super-family of the nuclear hormone receptors which act as ligand-regulated transcription factor to control a diverse set of essentials functions, such as growth development, metabolism, and reproduction. Though, the involvement of these receptors in several diseases including cancer was shown in numerous studies. Aim: Here, we reviewed the literature to report genetic polymorphisms and mutations investigated in the ESR genes (α and β) and to explore their relationship and their potential role to develop some diseases as well as the ER expression status especially in cancer. Methods: We searched the MEDLINE database with the keywords of estrogens receptors gene polymorphisms, short tandem repeat (STR) sequences, single-nucleotide polymorphisms (SNPs), cancer risk and diseases susceptibility. Results: The functional effects of some mutations, short nucleotide polymorphisms and STR polymorphisms of ESR gene on susceptibility of multiple diseases, especially on cancer risk, are well approved. Conclusions: The involvement of genetic variations of the ERs in the risk of multiples diseases is frequently established, which incite to more elucidate the functional role of these markers in cell. Therefore, further investigations are needed to see the impact of these variations in drug response which makes them suitable therapeutic.

Association of EGFR and HER2 Polymorphisms with Risk and Clinical Features of Thyroid Cancer

The epidermal growth factor receptor family plays a critical role in the control of many physiological processes. Genetic alterations and/or variations in the gene encoding these receptors have been implicated in a variety of human cancers. In this study we evaluate the association of two single-nucleotide polymorphisms (SNP), R497K and I655V, of the EGFR and HER2 genes, respectively, with thyroid cancer risk. The analysis was performed with 302 healthy individuals and 106 thyroid cancer patients. No significant difference was found in the allelic and genotypic frequency distribution of the SNP R497K between the control and patient groups. While for the SNP I655V, the allele G is more frequent in patients than in controls and was associated with an increased risk of thyroid cancer (odds ratio = 1.88; 95% confidence intervals: 1.18-3.01; p = 0.007). We have also investigated the relationship between these two polymorphic sites and clinicopathological characteristics such as thyroid-stimulating hormone level, off-thyroxin, serum thyroglobulin, tumor histology, metastasis, tumor status, tumor stage, and survival. No significant association was observed. Tumor status was found significantly associated with HER2 I655V as well as with two previously studied markers in the thyroid hormone receptor A and estrogen receptor 1 (ESR1) genes (D17S2189 and D6S440, respectively). We also report a correlation between thyroglobulin level and genotypes for SNP rs2228480 in exon 8 of the ESR1 gene. In conclusion, our results suggest that the SNP HER2 I655V, but not the EGFR R497K, was associated with thyroid cancer risk.

SNP marker analysis for validating the authenticity of Tunisian olive oil.

Olive (Olea europaea L.), which is an important oilproducing crop, is one of the oldest agricultural plant in the Mediterranean basin. The oil obtained is known for its nutritional and healthy benefits compared to other vegetable oils, and can be consumed in its crude form (Roche et al. 2000; Elloumi et al. 2012). Moreover, the olive oil sector plays an important role in the culture and socio-economy of many Mediterranean countries, including Tunisia. Traditionally, genetic variation analyses relying on morphological and chemical markers are insufficient to study the relationship and traceability between cultivars due to the environmental effect on the possibly large phenotype and the chemical composition, thus making it expensive (Busconi et al. 2003; Ben-Ayed et al. 2009, 2013). Recently, several molecular marker types, such as random amplified polymorphic DNA (RAPDs) (Busconi et al. 2003), amplified fragment length polymorphisms (AFLPs) (Pafundo et al. 2005; Grati Kamoun et al. 2006), simple sequence repeats (SSR) (Testolin and Lain 2005; Rekik et al. 2008; Ben-Ayed et al. 2009, 2012, 2014) and single nucleotide polymorphism (SNP) (Reale et al. 2006; Consolandi et al. 2008; RekikHakim et al. 2010) have been developed. These can be used as both detection of DNA polymorphisms and for effective distinction between different cultivars, thus solving traceability without any environmental influence. Despite the potential advantages of using SNPs for the authentication of major crop species as coffee (Spaniolas et al. 2006), to the best of our knowledge, the identification of SNP markers has not yet been documented in olive oil. Compared with other genetic markers, SNPs are beneficial from a technological viewpoint change in a single nucleotide allows the distinction of very similar cultivars. Moreover, these molecular markers requiring short DNA amplicons for genotyping and are genetically stable; their high density

Genetic features of thyroid hormone receptors.

Thyroid hormone receptors (TR) are prototypes of nuclear transcription factors that regulate the expression of target genes. These receptors play an important role in many physiological processes. Moreover, a dysfunction of these proteins is often implicated in several human diseases and malignancies. Here we report genetic variations and alterations of the TRs that have been described in the literature as well as their potential role in the development of some human diseases including cancers. The functional effects of some mutations and polymorphisms in TRs on disease susceptibility, especially on cancer risk, are now established. Therefore, further investigations are needed in order to use these receptors as therapeutic targets or as biological markers to decide on appropriate forms of treatment.