Do smoking and polymorphisms in xenobiotic metabolizing enzymes affect the histological stage and grade of bladder tumors?

Cigarette smoking and genetic susceptibility are the two factors most closely associated with bladder cancer development. This study sought to determine the effect of smoking and genetic polymorphisms in xenobiotic metabolizing enzymes on the histological stage and grade of bladder tumors in Tunisian patients. A total of 97 patients with urothelial cell carcinomas were examined with respect to smoking status, NAT2 (N-acetyltransferase 2), GSTM1 and GSTT1 (glutathione S-transferase Mu 1 and teta 1) genotypes distribution. Our data have reported that tobacco; NAT2, GSTM1 and GSTT1 genotypes were not associated with bladder tumor stage. When we studied the superficial bladder tumor group, we have shown that in smokers tobacco was associated with the development of low-grade tumors. Conversely, non-smoker patients carrying altered NAT2 genotypes were with a 3.67-fold increased risk of developing superficial high-grade tumors (P = 0.02; RR = 3.67; 95% CI: [1.40-9.62]).

Interleukin 10 promoter region polymorphisms in inflammatory bowel disease in Tunisian population.

OBJECTIVE: To test whether IL-10 promoter region polymorphisms are associated with susceptibility to inflammatory bowel disease, we examined the contribution of interleukin- 10 (IL-10) gene polymorphisms to Crohn's disease (CD) and Ulcerative colitis disease (UC) occurrence and also to CD phenotype. MATERIELS AND METHODS: SNPs at positions -627 (C > A) and -1117 (G > A) in the IL-10 promoter were determined in a sample of 105 Tunisian patients with IBD (75 CD and 30 UC) and 90 matched healthy controls. RESULTS: The 627 CA genotype is associated with ileal location (p = 0.015) and with stricturing (p = 510-3) and penetrating (p = 310-3) presentation of CD. An additive effect between IL10 variants and CARD15 3020 insC mutation (p = 0,006) on severe forms of CD was shown. CONCLUSIONS: In Tunisian population, the 3020insC insertion in NOD2/CARD15 gene is a marker of susceptibility to CD, while the A allele at position -627 in the IL-10 promoter increases the risk of CD ileal location and severe disease presentation. A genetic epistasis between IL-10 gene polymorphisms and CARD15/NOD2 gene mutation was suggested.

3020insC insertion in NOD2/CARD15 gene, a prevalent variant associated with anti-Saccharomyces cerevisiae antibodies and ileal location of Crohn's disease in Tunisian population.

OBJECTIVE: Our aim is to investigate the relation between CARD15 3020insC mutation, anti-Saccharomyces cerevisiae antibodies (ASCA) and disease phenotype, in Tunisian inflammatory bowel disease (IBD) patients. MATERIALS: A hundred Tunisian patients with IBD (75 Crohn's disease CD and 25 ulcerative colitis UC) and 60 matched healthy controls were studied. METHODS: CARD15 mutation was analysed by using an allele-specific polymerase chain reaction and sequencing. Assessment of ASCA in serum was performed by ELISA. RESULTS: The frequency of the mutation was significantly higher in Crohn's disease than in control (p = 0,0005; OR = 20.45; CI 95% = 2.86-413.85) and did not differ statistically in UC group (p = 0, 05) from control. ASCAs were present in 60% of CD and 20, 8% of UC. CONCLUSION: This study suggests that in northern Tunisian population, 3020insC mutation in NOD2/CARD15 gene is a prevalent mutation leading to the typical Crohn's disease including ileal location, stricturing and penetrating clinical types and ASCA expression.

No evidence of the APC D1822V missense variant's pathogenicity in Tunisian patients with sporadic colorectal cancer.

OBJECTIVES: Sporadic colorectal cancer is influenced by numerous single nucleotide polymorphisms (SNPs), each with minor effects on the cancer risk. This study seeks to determine whether there is any association of the I1307K, E1317Q and D1822V variants within the Adenomatous polyposis coli gene (APC) and risk to develop colorectal cancer in Tunisian population. METHODS: Direct sequencing was used to investigate three SNPs in the APC in 48 Tunisian sporadic colorectal cancer cases and 63 controls. RESULTS: There was no statistically significant association between the I1307K, E1317Q and D1822V variants investigated and colorectal cancer risk. CONCLUSION: The lack of association may show that these variants selected for this study are not involved in the colorectal carcinogenic process. Otherwise, the eventual biological effect is so little to go undetected, unless increasing the sample size.

Detection of cytokeratin 19 mRNA and CYFRA 21-1 (cytokeratin 19 fragments) in blood of Tunisian women with breast cancer.

Cytokeratin 19 (CK19) is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells. It is highly expressed by all epithelial cells and represents a useful indicator of epithelial differentiation. The soluble fragment of CK19 (CYFRA 21-1) can be a useful circulating tumor marker and can be detected in the serum of cancer patients. The development of metastasis in patients with cancer of epithelial origin is due to the migration of tumor cells from the original tumor to distant organs. In order to detect micrometastasis in patients with breast cancer, we evaluated and compared CK19 gene expression using RT-PCR in blood samples collected from 80 healthy women and 80 patients with localized or metastatic breast cancer. The concentration of the soluble CK19 fragment CYFRA 21-1 was measured in serum of all study subjects by radioimmunoassay employing specific monoclonal antibodies. The relationship between the expression of this molecular marker and clinical stage, tumor differentiation and CK19 mRNA transcripts was investigated. We found that CK19 mRNA expression in blood (as a direct index of the presence of circulating tumor cells) was not correlated with CYFRA 21-1.