Role of VDR gene polymorphisms and vitamin D levels in normal and overweight patients with PCOS.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women. In recent years, the effects of vitamin D receptor (VDR) gene variants and VitD3 levels on clinical features of PCOS have been frequently described. In this study, we aimed to determine the relationship between VDR ApaI, TaqI and Cdx2 gene variants and VitD3 levels in PCOS patients. Patients were divided into two groups: BMI<25 and BMI>=25. VDR genotypes were determined by real-time polymerase chain reaction (PCR) and serum VitD3 levels were examined by ELISA. We observed that frequencies of the Apa1 AC genotype, C allele and Cdx2 T allele are increased in the BMI>=25 group compared to BMI<25 group. Also, the ApaI C allele, Taq1 AA genotype and A allele, Cdx2 CC genotype and C allele are associated with increased triglyceride, total cholesterol, LDL-cholesterol levels in patients with BMI>=25. When examining the relationship between VitD3 levels and clinical profiles in all PCOS patients, regardless of BMI distinction, it is determined that there is a positive correlation between LDL-cholesterol and ftestosterone levels. The present findings suggest that VDR variants are one of the most important risk factors for PCOS, especially for patients with BMI>=25.

Investigation of ABCA1 C69T polymorphism in patients with type 2 diabetes mellitus.

INTRODUCTION: Non insulin dependent diabetes mellitus is the most common type of diabetes. Genetic factors, lipid profiles, hypertension are potential risk factors for diabetes mellitus. Adenosine binding cassette transporter proteins 1 (ABCA1) plays a role in cholesterol metabolism, especially high density lipoprotein (HDL-cholesterol). There are multiple mechanisms by which HDL-cholesterol can be atheroprotective, it is clear that the relative activity of ABCA1 plays a major role. We aimed to investigate association of ABCA1 C69T gene polymorphism with lipid levels in Turkish type 2 diabetic patients. MATERIALS AND METHODS: After isolation of DNA by ethanol precipitation we determined ABCA1 gene polymorphism by using polimerase chain reaction--restriction fragment lenght polymorphism (PCR-RFLP) method in 107 type 2 diabetic patients and 50 healthy controls. RESULTS: We have observed that the frequency of TT genotype is significantly higher in healthy controls compared to patients (14% vs. 3%; P = 0.008). Also frequency of T allele was higher in controls than in patients (34% vs. 21%; P = 0.020; OR (95% CI) = 0.52 (0.30-0.88)). There was no association of lipid levels and ABCA1 C69T polymorphism subgroups. CONCLUSION: We have found significantly higher frequency of both T allele and genotype in control group when compared to patients that made us think that T allele may be a protective factor against diabetes mellitus. But, we could not find a relationship between genotypes and lipid concentrations in our two groups. Larger studies will help us to understand the relationship between ABCA1 C69T genotype and lipid parameters in diabetes mellitus.

Association of vitamin D receptor Taq I polymorphism and susceptibility to oral squamous cell carcinoma.

BACKGROUND: It has been hypothesised that vitamin D receptor (VDR) gene polymorphisms may influence both the risk of cancer occurrence and prognosis. MATERIALS AND METHODS: The distribution of VDR Taq I polymorphism in 64 patients with OSCC was determined by polymerase chain reaction based restriction fragment length polymorphism (RFLP) and compared with that of 87 healthy controls. RESULTS: There was a significant difference in the distribution of VDR Taq I genotypes between OSCC patients and healthy controls. Patients with the VDR Tt genotype were found to be at significantly higher risk for OSCC than those with other genotypes (p=0.036). In particular, female OSCC patients were at higher risk (p<0.001) for oral cancer. CONCLUSION: These results suggest that the VDR Taq I polymorphism may be associated with susceptibility to OSCC. Female predilection of the OSCC risk in association with VDR gene polymorphism should also be investigated.

The influence of cyclin D1 A870G polymorphism on colorectal cancer risk and prognosis in a Turkish population.

BACKGROUND: Cyclin D1, encoded by the gene CCND1, is a regulatory protein in the cell cycle transition from G(1) phase to S phase. A common polymorphism (A870G) at codon 242 affects splicing of the CCND1 transcript and may cause uncontrollable cellular growth. The present study was performed to test the association between A870G polymorphisms in the CCND1 gene and colorectal cancer risk and progression. PATIENTS AND METHODS: The 870 A>G polymorphism in the cyclin D1 gene was genotyped in a Turkish colorectal cancer case-control population including fifty-seven cases (35 male, 22 female; mean age + or - SD: 59.33 + or - 13.7 years) and 117 controls (63 male, 54 female; mean age + or - SD: 54.4 + or - 12.2 years) using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Genotype frequencies of our patients and controls both confirmed to the Hardy-Weinberg equilibrium. There was no difference in the distribution of CCND1 genotypes and frequencies of the alleles A (59.6% versus 49.6%) and G (40.4% versus 50.4%) in the colorectal cancer patients and controls, respectively. Women homozygous for the cyclin D1 870 GG genotype showed an increased risk for developing colorectal cancer compared to those with the AG+AA genotypes and this result was statistically significant (OR 5.568, 95% CI 1.270-24.417, p=0.02). On the other hand, the cyclin D1 GA genotype was associated with distant metastasis (p=0.016). CONCLUSION: Our findings suggest that genetic variants of A870G might be associated with distant metastasis and also gender.

Is there any correlation between TNF-related apoptosis-inducing ligand (TRAIL) genetic variants and breast cancer?

INTRODUCTION: TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand and also a member of the TNF superfamily. We aimed to investigate the possible relationship between TRAIL and breast cancer. Here, we report the results of the first association study on genetic variation in the TRAIL gene and its effect on breast cancer susceptibility and prognosis. MATERIAL AND METHODS: A C/T polymorphism at 1595 position in exon 5 of the TRAIL gene was genotyped in a Turkish breast cancer case-control population including 53 cases (mean age: 55.09 ±11.63 years) and 57 controls (mean age: 57.17 ±17.48 years) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: There were no differences in the distribution of TRAIL genotypes and frequencies of the alleles in the breast cancer patients and controls. A heterozygous TRAIL CT polymorphism in exon 5 was present in 8.3% of tumour stage III-IV and 48.8% of stage I-II patients, and in 42.1% of controls. The reduced frequency of this genotype in patients who had advanced tumour stage was statistically significant (p = 0.017). CONCLUSIONS: Our findings indicate that genetic variants of TRAIL at position 1595 in exon 5 might be associated with progression of breast cancer.

Effects of manganase superoxide dismutase Ala-9Val polymorphism on prostate cancer: a case-control study.

BACKGROUND: Manganese superoxide dismutase (MnSOD) is a major enzyme that is responsible for the detoxification of reactive oxygen species in the mitochondria. Mitochondrial DNA damage may contribute to carcinogenesis as an important risk factor. The aim of this study was to investigate the relationship between prostate cancer and MnSOD Ala-9Val polymorphism in Turkish men with prostate cancer. PATIENTS AND METHODS: Fifty patients with prostate cancer and 50 healthy controls were included in this study. Gene polymorphism was determined using a PCR-RFLP method. RESULTS: The Ala/Ala genotype and the Ala allele were found at statistically higher frequencies in patients with prostate cancer as compared to controls (p < 0.05). The patients suffering from prostate cancer were divided into two groups according to Gleason score: aggressive prostate cancer and non-aggressive prostate cancer. It was observed that carrying the Ala/Ala genotype or the Ala allele resulted in an insignificant increase in the frequency of aggressive prostate cancer compared to nonaggressive prostate cancer. It was concluded that MnSOD Ala allele might be the cause of prostate cancer risk among alcohol users. CONCLUSION: The results of our study of Turkish prostate cancer patients suggest that mutation of the MnSOD gene may be an important risk factor for prostate cancer.

Investigation of NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T polymorphism in prostate cancer.

BACKGROUND: NAD(P)H:quinone oxidoreductase 1 (NQO1) is a part of the antioxidant defense system. NQO1 protects cells from oxidative stress by maintaining antioxidant forms of ubiquinone and vitamin E and this enzymatic activity can be sufficient to protect against carcinogenesis. Oxidative stress may contribute to carcinogenesis as an important risk factor. This study aimed to investigate the relationship between prostate cancer and NQO1 C609T polymorphism in a Turkish population. PATIENTS AND METHODS: Forty-five patients with prostate cancer and fifty healthy controls were included in this study. Gene polymorphism was determined by a restricted fragment length polymorphism-polymerase chain reaction (PCR-RFLP) method. RESULTS: The NQO1 TT genotype was demonstrated to be increased in patients, there were no significant differences between distributions of NQO1 C609T genotypes in the study groups. Serum PSA and alkaline phosphatase levels were elevated in patients carrying T alleles (TT > CT > CC). There were no correlations between tumor size, node classification, metastasis or stage and NQO1 genotypes. CONCLUSION: The results of our study of Turkish prostate cancer patients suggests that mutation of the NQO1 gene may effect the serum PSA and alkaline phosphatase levels. However there were no differences between the NQO1 genotypes in the study groups.