Contribution of microRNA-149, microRNA-146a, and microRNA-196a2 SNPs in colorectal cancer risk and clinicopathological features in Tunisia.

BACKGROUND AND AIM: Colorectal cancer (CRC) is a worldwide leading cause of mortality. Genetic studies have associated single nucleotide polymorphisms in genes encoding microRNAs with CRC risk but results are mostly inconclusive across variable ethnicities. In this study, we investigated the association of hsa-mir-149 rs2292832 C/T, hsa-mir-146a rs2910164 G/C and hsa-mir-196a2 rs11614913 C/T and explored their roles in clinicopathological features of CRC progression in an Eastern Tunisian cohort. SUBJECTS AND METHODS: Three hundred thirteen subjects were enrolled in our retrospective study including 152 CRC cases and 161 controls. Genotyping was assayed by RFLP-PCR (Restriction Fragment Length Polymorphism-Polymerase Chain Reaction) method. SPSS v.18.0, R and SNP Stats online software performed statistical analysis. RESULTS: Significantly higher hsa-mir-149C/T rs2292832 minor allele frequency was associated with increased risk of CRC [p = .03; OR = 1.54 (1.08-2.19)]. In addition, significant crude associations of hsa-mir-149C/T rs2292832 polymorphism were detected under codominant, dominant and additive models of inheritance. After adjusting for covariates and performing FDR correction, these associations did not remain. No associations were detected for hsa-mir-146a G/C rs2910164 and hsa-mir-196a2 C/T rs11614913. When performing stratified analysis of clinicopathological features according to genotypes, a significant association (p = .004) was found between hsa-mir-146a G/C rs2910164 and tumour differentiation grade. Regression analysis according to CRC progression features had demonstrated a trend toward significance in overdominant model of inheritance for hsa-mir-149C/T rs2292832 with a protective effect [p = .05; OR = 0.51 (0.26-1.02)]. CONCLUSION: Hsa-mir-149C/T rs2292832 and hsa-mir-146a G/C rs2910164 may influence CRC risk in an ethnicity-dependent manner by interfering with CRC progression parameters in Tunisian cohort.

Effect of thymoquinone on 1,2-dimethyl-hydrazine-induced oxidative stress during initiation and promotion of colon carcinogenesis.

We evaluated pre- and post-thymoquinone (TQ) treatment on 1,2-dimethyl-hydrazine (DMH)-induced oxidative stress during initiation and promotion of colon carcinogenesis. Wistar rats were induced with DMH (20mg/kg) for 10 or 20 weeks, and treated with TQ (5mg/kg). Following sacrifice, the colons were analysed for tumour development, reactive oxygen species (ROS) generation, lipid peroxidation [conjugated diene (CD) and malondialdehyde (MDA)], antioxidants [glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH)], and histological changes. Increased ROS levels and lipid peroxidation were seen during tumour initiation and promotion. All ROS-scavenging enzyme activities were increased upon shorter DMH treatment but not following longer treatment, while GSH amount was increased upon both treatments. Oxidative state perturbations were associated with moderate colon dysplasia and 30% tumour incidence at initiation and marked dysplasia and 100% tumour incidence at promotion. TQ pre-treatment restored completely DMH-induced oxidative stress at initiation and established histological changes and tumour development. It also abrogated oxidative status aggravation at promotion, and significantly reduced tumour incidence (67%). By comparison, TQ post-treatment corrected oxidative status and attenuated tumour development at initiation. It slightly reduced MDA and antioxidant level at promotion, with a slight reduction in tumour state and dysplasia degree. TQ is efficacious in protecting and curing DMH-induced initiation phase of colon cancer, while exerting a protective role at promotion. TQ effect seems to be related to its capacity in preventing DMH-induced oxidative stress. These in vivo results support the notion that TQ may be of value as a chemo-preventive alternative in colorectal cancer patients.

Nutritional fatty acid quality of raw and cooked farmed and wild sea bream (Sparus aurata).

The effects of steaming, grilling, and frying in corn and sunflower oils, respectively, on the fatty acid compositions of farmed and wild sea bream were evaluated. The lipid content increased with frying in both oil types. The maximum moisture value was found in steamed fish (P<0.05). Fried sea bream in corn and sunflower oils contained a lower content of n-3 polyunsaturated fatty acids (P<0.05) (3.87 and 5.32% of total fatty acids (TFA) in farmed fish and 2.96 and 2.14% TFA in wild fish). The n-3/n-6 ratio decreased significantly after cooking, particularly after frying in corn and sunflower oils, respectively: from 2.51 to 0.08 and 0.12 in farmed fish and from 0.94 to 0.06 and 0.04 in wild fish. The trans fatty acid levels remain stable after steaming and grilling, but they were significantly affected by frying. Our results reveal that the cooking process has considerable effect on the fatty acid compositions of farmed and wild sea bream.