Haplotype analysis of p53 polymorphisms: Arg72Pro,Ins16bp and G13964C in Tunisian patients with familial or sporadic breast cancer

Background: The p53 polymorphisms have been extensively studied as putative breast cancer susceptibility variants. The present study was undertaken to investigate the association of p53 Arg72Pro, Ins16bp and G13964C polymorphisms and their haplotypes with breast cancer risk in Tunisian women. Methods: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 159 patients and 132 controls. Results: The G13964C intronic variant was significantly associated with familial breast cancer risk (p = 0.0018) while the genotypic distribution was similar for p53 Arg72Pro and Ins16bp in patients and controls. Moreover, the (NoIns-C), (Arg-C) and (NoIns-Arg-C) haplotypes were significantly associated with familial breast cancer risk (p = 0.0021, p = 0.0096 and p = 0.0084, respectively) while there was a trend of association between the (Ins-Arg) and (Ins-Arg-G) haplotypes and the risk of sporadic breast cancer. Only the G/C genotype as well as the (NoIns-C) haplotype remained significant after correction for multiple testing. Conclusion: Our data revealed an association between the G/C genotype and the (NoIns-C) haplotype and the risk of familial breast cancer in Tunisian women. However, these observations need to be confirmed due to the limited statistical power of our study and the small number of cases.     

Identification of novel candidate genes by exome sequencing in Tunisian familial male breast cancer patients

Molecular Biology Reports - Male Breast Cancer (MBC) is a rare and aggressive disease that is associated with genetic factors. Mutations in BRCA1 and BRCA2 account for...     

Study of the Bacillus thuringiensis Vip3Aa16 histopathological effects and determination of its putative binding proteins in the midgut of Spodoptera littoralis

The bacterium Bacillus thuringiensis produces, at the vegetative stage of its growth, Vip3A proteins with activity against a broad spectrum of lepidopteran insects. The Egyptian cotton leaf worm (Spodoptera littoralis) is an important agricultural pest that is susceptible to the Vip3Aa16 protein of Bacillus thuringiensis kurstaki strain BUPM95. The midgut histopathology of Vip3Aa fed larvae showed vacuolization of the cytoplasm, brush border membrane destruction, vesicle formation in the apical region and cellular disintegration. Biotinylated Vip3Aa toxin bound proteins of 55- and 100-kDa on blots of S. littoralis brush border membrane preparations. These binding proteins differ in molecular size from those recognized by Cry1C, one of the very few Cry proteins active against the polyphagous S. littoralis. This result supports the use of Vip3Aa16 proteins as insecticidal agent, especially in case of Cry-resistance management.     

Negative/low HER2 expression alone or combined with E-cadherin positivity is predictive of better prognosis in patients with breast carcinoma

The loss of E-cadherin expression leads to absence of tissue integrity, an essential step in tumor progression. Methylation of CpG islands in the promoter region of the CDH1 gene coding E-cadherin might be an alternative for gene silencing. In the present study, we investigate the expression of E-cadherin and hormone receptors in invasive ductal breast carcinoma (IDCs). Protein expression was analysed immunohistochemically in 87 cases, including 26 familial tumors. The most interesting results revealed a significantly reduced E-cadherin expression in cases with familial history compared to sporadic tumors (p=0.009), as well as with tumors ≤5 cm (p=0.022). Moreover, HER2 over-expression was associated with distant metastasis (p=0.011) and overall survival (p log rank=0.028). Tumors displaying negative/low HER2 expression combined with E-cadherin positivity confer better patient survival (p=0.052). Triple Negative tumors (TN) were more frequently found in patients with advanced grade (GIII) (p=0.001) and TNM (III+IV) (p=0.018) which supports the aggressive behavior of TN tumors. On the other hand, hypermethylation of CDH1 gene promoter was observed in 46% of hereditary cases and strongly associated with loss of E-cadherin expression (p=0.002). Furthermore, patients with unmethylated CDH1 pattern have a better 5-year disease free survival (p=0.021). In conclusion, in patients with hereditary breast cancer, the CpG methylation event contributes to the loss of E-cadherin expression. On the other hand, HER2 over-expression is predictive of worse prognosis, either alone or combined with loss of E-cadherin expression in Tunisian patients with breast cancer.     

(AC) dinucleotide repeat polymorphism in intron 1 of human EGFR shows ethnic specificities and high evidence for association with breast cancer

A polymorphic AC repeat in intron 1 of the EGFR gene was genotyped on 352 healthy individuals and 118 women with breast cancer sampled from the Kuwaiti and Tunisian populations. We compared allele frequencies in these populations with published data on various ethnic groups. We found very close similarity between Tunisian and Kuwaiti populations for both allelic and genotypic frequencies and in both control and patient groups. Our analysis revealed clear interethnic differences between populations; in Europeans, allele 16 occurred predominantly, whereas in Tunisia and Kuwait allele 17 was the most frequent and allele 20 predominated in Asians. One hundred twenty-three healthy women, matched with the 118 breast cancer patients, were used as controls to test for associations between AC repeat and cancer risk. Strong evidence for such an association was found for allele 18 when considered alone (chi2=27.04, corrected p=0.0000016, OR=3.94) or with longer alleles (>17 repeats) (chi2=20.21, p=0.0005, OR=2.30). This contrasts with Asian populations where allele 16 was identified as the risk allele, showing allele heterogeneity depending on ethnicity.     

Toxicological Study and Oxidative Stress Evaluation for Safety Assessment of <Emphasis Type="Italic">Bacillus thuringiensis</Emphasis> Vip3Aa16 Toxin in Adult Mice

Vegetative insecticidal proteins were produced by some Bacillus thuringiensis strains and were successfully used in biological control against different agricultural pests such as Lepidoptera. To assess the safety of Vip3Aa16 toxins in mammalian organisms, we evaluated their toxicity using histological, hematological, and oxidative stress parameters on albino Swiss mice. The animals were orally treated with 2500, 5000, 7500 milligrams (mg) of the toxin/kilogram (kg) of body weight for 14 days. Then samples of blood, kidney and hepatic tissues were collected at the end of the treatment. Hematological parameters were monitored by RBC, WBC, hemoglobin, hematocrit, MCV, MCH, and MCHC. Liver and kidney MDA, SOD, vitamin C and H₂O₂ were analyzed to assess oxidative damage. Hepatotoxicity was monitored by analysis of the plasma enzymes ALT and AST and bilirubin levels. Renal toxicity was tested by urea, uric acid and creatinine evaluation. The histopathology of kidney and liver tissues was also investigated. The results of the toxicological study revealed that the Vip3AaA16 has no lethal effect since no mortality was observed at any dose. Moreover, body weight, hematological, histological, biochemical and oxidative findings showed no significant differences between treated and control groups. All these findings confirmed that this toxin is highly safe and doesn’t represent any risk on animal health and subsequently, Vip3Aa16 toxin can be safely used in biological programs to control Lepidopteran pests attacking crops around the world.