Association between estrogen receptor a gene polymorphism and the risk of breast cancer in a group of Egyptian women

Estrogen receptor [ER] is a ligand-activated transcription factor that mediates estrogen actions in target tissues. Several common polymorphisms of the ER-alpha gene have been reported to be associated with alterations in receptor expression and function. We evaluated the hypothesis that genetic polymorphisms in the ER-alpha gene may be associated with breast cancer risk in Egyptians. In this study the involvement of two RFLPs at the ER-alpha gene locus, denoted as PvuII and XbaI in breast cancer were examined in 40 breast cancer cases and 33 age frequency-matched controls. A case-control comparison was performed and the genotype distributions examined according to different tumor and population parameters. PvuII polymorphism was associated with an increased risk of breast cancer [OR = 5.14, P=0.01], while there was no significant difference in genotype frequency of the XbaI polymorphism between controls and cases. The PvuII polymorphism was also associated with elevated breast cancer risk in premenopausal cases [OR=7.00, p=0.049]. In addition, significant association was found in patients with LN metastasis carrying the ER-alpha PvuII T allele [OR=7.14, p=0.013]. These results suggest that biomarkers for genetic polymorphisms could be used for the identification of breast cancer risk among Egyptian women

Human resistin gene polymorphism: association with serum resistin level and insulin resistance in type 2 diabetes mellitus

Resistin is an adipocyte - secreted cytokine associated with insulin resistance in rodents. In humans, it remains controversial whether circulating resistin levels are associated with insulin resistance, type 2 diabetes, or obesity. The role of resistin gene, referred to RETN, in human type 2 diabetes or obesity is largely unclear in studies of its association with SNPs or serum resistin. Major genetic factors of type 2 diabetes, a probable polygenic disease, remain to be identified. Therefore the aim of our work was to study circulating level of resistin and to correlate this level with resistin gene 3'UTR+62G-A polymorphism and factors related to insulin resistance in type 2 diabetic patients. 40 male patients with type 2 diabetes [group I] and 10 age-matched healthy controls [group II] were included. All patients and controls were subjected to full history taking, clinical examination stressing on waist circumference, BMI and blood pressure. Laboratory investigations included lipid panel [TG, total cholesterol, HDL-C and LDL-C], glycemic parameters [FBS, Hb A1c, fasting insulin, HOMA, IR], serum uric acid, highly sensitive CRP, serum resistin and molecular detection of resistin gene 3'UTR+62G-A polymorphism using PCR-RFLP. Serum resistin levels, highly sensitive CRP, anthropometric measures and metabolic parameters were significantly higher in type 2 diabetic patients [group I] than in healthy controls [group II] [P<0.05]. In type 2 diabetic patients the serum resistin was negatively correlated with HDL-C and positively correlated with BMI, HOMA-IR and highly sensitive CRP [P < 0.05]. In diabetic subjects the genotype distributions of resistin gene 3'UTR polymorphism were as follows: 3 [7.5%] subjects were heterozygous [GA], 1 [2.5%] was homozygous [AA] for the mutant allele and 36 [90%] were homozygous [GG] for the wild allele. Type 2 diabetic subjects had a significantly lower frequency of resistin gene 3'UTR + 62A variant [GG: GA/AA, 90%:10%] than control subjects [GG: GA/AA, 60%:40%; odds ratio, 6.0; 95% confidence interval, 1.17 to 30.7; P = 0.041]. G allele was linked to greater insulin resistance as indicated by higher HOMA-IR index [P = 0.004]. Also diabetic subjects harboring the G allele showed significant higher levels of serum resistin, BMI, highly sensitive CRP as well as a significant decrease in HDL-cholesterol [P = 0.042, 0.007, 0.008, 0.003 respectively]. These findings suggest that resistin gene 3'UTR + 62G-A is associated with serum resistin level and may play a role in the pathogenesis of type 2 diabetes and insulin resistance. The strong correlation of resistin with highly sensitive CRP suggests that resistin may be considered as inflammatory marker associated with type 2 diabetes

Study of genetic predisposition in Egyptian colorectal cancer patients: role of phase II xenobiotic metabolizing genes polymorphism

The glutathione S-transferase [GST] supergene family is an important part of cellular enzyme defense against endogenous and exogenous chemicals, many of which have carcinogenic potential. The present investigation was conducted to evaluate the possible association between genetic polymorphisms of glutathione S-transferase M1 and T1 [GSTM1 and GSTT1], and susceptibility to colorectal cancer and the interaction with environmental factors. A case-control study of 50 patients and 50 healthy controls was conducted to investigate the role of GSTM1 and GSTT1 polymorphisms in colorectal cancer. Genotypes of GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction [PCR]. The frequencies of GSTM1 null and GSTT1 null genotypes in controls were 42% and 16%, respectively. The GSTM1 polymorphism was associated with an increased risk of developing colorectal cancer [p=0.002; OR=3.9, 95% CI 1.68- 9.15]. There was no significant association between GSTT1 null genotype and colorectal cancer risk. The GSTT1 deletions was associated with an increased risk of developing distal tumour [OR =5.25, 95% CI: 1.6-16.7, p=0.006]. GSTM1 null genotype was significantly more common in patients who were diagnosed before the age of 40 years than in those who were diagnosed at an older age. This suggests that the GSTM1 genotype might influence the age of onset of colorectal cancer. In conclusion, the results of the present study suggest that GSTM1 null genotype and combined GSTM1/T1 null genotypes may confer a genetic susceptibility to colorectal cancer. In addition, other environmental factors such as smoking may also have a contributing role