Association between ABCB1, ABCG2 carrier protein and COX-2 enzyme gene polymorphisms and breast cancer risk in a Turkish population.

AIM: Breast cancer is the most common cancer and the second leading cause of cancer-related deaths among women. Several genetic and environmental factors are known to be involved in breast cancer pathogenesis, but the exact etiology of this disease is complicated and not completely understood. We aimed to investigate whether the gene polymorphisms of ABCB1 and ABCG2 carrier proteins and COX-2 enzyme affect breast cancer risk. METHOD: ABCG2 C421A (rs2231142), ABCB1 C3435T (rs1045642), COX-2 T8473C (rs5275) and COX-2 G306C (rs5277) were genotyped 104 breast cancer patients and 90 healthy controls using a real-time PCR for breast cancer susceptibility. RESULTS: Patients carrying ABCG2 C421A, the CC genotype, had a higher risk of disease compared with patients carrying any A allele (OR = 3.06; 95% CI = 1.49-6.25, p = 0.0019). The other variants showed no association with breast cancer (p > 0.05). Comparing the pathological parameters with the variants, only, the frequency of C allele of ABCB1 C3435T was significantly lower in the estrogen receptor-α (ERα) (OR = 2.25; 95% CI: 0.75-6.76; p = 0.041) and progesterone receptor (PgR) (OR = 3.67; 95% CI: 1.34-10.03; p = 0.008) positive breast cancer patients. CONCLUSION: ABCB1 C3435T and ABCG2 C421A might represent a potential risk factor for breast cancer for Turkish women.

Genetic Variations in Phospholipase C-epsilon 1 (PLCE1) and Susceptibility to Colorectal Cancer Risk.

Colorectal cancer (CRC) is the third most common cause of cancer-related mortality and causes almost a million deaths worldwide each year. Genetic and environmental factors have gained importance in CRC as well as other types of cancer due to contribution to development of malignancies. Phosholipase C-epsilon 1 PLCE1 is one of the phospholipase family of enzymes and controls cellular responses leading to cell growth, differentiation and gene expression. Therefore, it was evaluated the effects of PLCE1 variations on developing CRC. Rs2274223 was significantly associated with CRC risk (OR = 2.018) while rs3765524 did not significantly differ (p > 0.05). The findings are the first results of PLCE1 profiles in the Turkish and could provide an understanding of aetiology in CRC.

Benomyl induced oxidative stress related DNA damage and apoptosis in H9c2 cardiomyoblast cells.

Benomyl, benzimidazole group pesticide, has been prohibited in Europe and USA since 2003 due to its toxic effects and it has been still determined as food and environmental contaminant. In the present study, the toxic effect mechanisms of benomyl were evaluated in rat cardiomyoblast (H9c2) cells. Cytotoxicity was determined by MTT and NRU assay and, oxidative stress potential was evaluated by reactive oxygen species (ROS) production and glutathione levels. DNA damage was assessed by alkaline comet assay. Relative expressions of apoptosis related genes were evaluated; furthermore, NF-κB and JNK protein levels were determined. At 4 µM concentration (at which cell viability was >70%), benomyl increased 2-fold of ROS production level and 2-fold of apoptosis as well as DNA damage. Benomyl down-regulated miR21, TNF-α and Akt1 ≥ 48.75 and ≥ 97.90; respectively. PTEN, JNK and NF-κB expressions were upregulated. The dramatic changes in JNK and NF-κB expression levels were not observed in protein levels. These findings showed the oxidative stress related DNA damage and apoptosis in cardiomyoblast cells exposed to benomyl. However, further mechanistic and in vivo studies are needed to understand the cardiotoxic effects of benomyl and benzimidazol fungucides.