Haplotype Analysis of Vitamin D Receptor (VDR) Gene in Breast Cancer Patients.

BACKGROUND: The aim of the study was to evaluate the role of well-characterized vitamin D receptor (VDR) gene polymorphisms, BsmI (rs 1544410), ApaI (rs 7975232), TaqI (rs 731236), and FokI (rs 10735810) and their haplotypes in the pathogenesis of breast cancer in Turkish women. METHODS: The subjects consisted of women including 331 breast cancer patients and 345 healthy controls. After conventional DNA isolation genotyping was done by a PCR-RFLP method, haplotype analysis was performed using Haploview 4.2. RESULTS: Haplotype analysis in different combinations revealed that frequencies of Fbt, fbt, bAt, and bt haplotypes are significantly higher in breast cancer patients than controls (χ2 = 6.862, p = 0.0088; χ2 = 4.176, p = 0.041; χ2 = 4.184, p = 0.0408; χ2 = 8.409, p = 0.0037 respectively). However, no statistically significant difference between genotypes of cases and controls were found when analyzed separately. CONCLUSIONS: All these data support the hypothesis that it is crucial to evaluate VDR gene polymorphism by haplotype analysis in order to understand how changes in VDR sequence influence the function of the VDR gene and how this variability affects the risk of breast cancer.

Regional Clinical and Biochemical Differences among Patients with Primary Hyperparathyroidism.

BACKGROUND: Environmental habitat may play a role in clinical disparities of primary hyperparathyroidism (pHPT) patients. AIMS: To compare preoperative clinical symptoms and associated conditions and surgical findings in patients with pHPT, living in different geographical regions from the Black Sea, Mediterranean and Anatolia regions. STUDY DESIGN: Retrospective, clinical-based multi-centric study of 694 patients with pHPT. METHODS: Patients from 23 centers and 8 different geographical regions were included. Data related to baseline demographics, clinical, pathologic and treatment characteristics of 8 regions were collected and included age, gender, residential data, symptoms, history of fracture, existence of brown tumor, serum total Ca and p levels, serum parathormone (PTH) levels, serum 25-OH vitamin D levels, bone mineral density, size of the resected abnormal parathyroid gland(s), histology, as well as the presence of ectopia, presence of dual adenoma, and multiple endocrine neoplasia (MEN)- or familial-related disease. RESULTS: The median age was 54. Asymptomatic patient rate was 25%. The median PTH level was 232 pg/mL and serum total Ca was 11.4 mg/dL. Eighty-seven percent of patients had an adenoma and 90% of these had a single adenoma. Hyperplasia was detected in 79 patients and cancer in 9 patients. The median adenoma size was 16 mm. Significant parameters differing between regions were preoperative symptoms, serum Ca and p levels, and adenoma size. All patients from South-East Anatolia were symptomatic, while the lowest p values were reported from East Anatolia and the largest adenoma size, as well as highest Ca levels, were from Bulgaria. CONCLUSION: Habitat conditions vary between geographical regions. This affects the clinicopathological features of patients with pHPT.

Multidisciplinary breast cancer teams and proposed standards.

Multidisciplinary approach is recommended for the diagnosis and treatment of cancer, in order to optimize quality of life and survival. Multidisciplinary cancer teams that are used for this purpose enable communication between professionals. Multidisciplinary cancer meetings are pre-programmed regular meetings where cancer patients are evaluated on an individual basis, and where the multidisciplinary treatment of patients is planned based on evidence. Currently, application of appropriate treatment in a timely manner carries as great significance as early diagnosis. For this purpose, standards of multidisciplinary approach are significant. Disease specific multidisciplinary breast cancer meetings are essential in the treatment of breast cancer. The standards and organization of these teams have been scientifically determined. It is recommended that these multidisciplinary breast cancer meetings should be held regularly and the required infrastructure should be provided.

Comparison of the histopathology and prognosis of bilateral versus unilateral multifocal multicentric breast cancers.

BACKGROUND: Multiple breast cancers may present with different clinical and biological characteristics. The data indicate that multifocal (MF), multicentric (MC), and bilateral synchronous (BS) breast cancers (BC) are more aggressive and have an equivalent or moderately poorer survival rate compared with unilateral cases. However, a comparison of these multiple breast cancers has not been covered in the literature. The aim of this study was to describe the histopathological characteristics of patients suffering from MF, MC, and BS breast carcinoma and to compare their prognoses. METHODS: Retrospective data for MF, MC, and BS breast carcinoma patients treated in five different breast cancer units in Turkey between 2003 and 2012 were collected. MF and MC cancers were defined as more than one lesion in the same quadrant or in separate quadrants, respectively. RESULTS: There were 507 patients (271 MF, 147 MC, and 89 BS) treated in this time period. BS breast carcinoma patients were younger than the other groups (44.83 ± 9.6, 47.27 ± 11.6, and 51.11 ± 11.8 years for BS, MF, and MC breast carcinoma patients, respectively). MFBC and MCBC patients in this study were younger than the ages reported in Western literature, but this result was similar to the ages reported in Eastern literature. The five-year survival rates and recurrence rates were not statistically different among groups (P = 0.996 and P = 0.263, respectively). According to univariate analyses, tumor size, histological grade, and lymph node status were statistically significant factors that affected survival. However, only lymph node involvement was significant for survival according to multivariate analyses. CONCLUSIONS: The clinical significance of MF, MC, and BS breast cancers is still unclear and their influence on prognosis is controversial. Disease-free and overall survival rates of BS breast cancers might be similar to MF and MC breast cancers.

Predicting the likelihood of nonsentinel lymph node metastases in triple negative breast cancer patients with a positive sentinel lymph node: Turkish Federation of Breast Disease Associations protocol MF09-01.

BACKGROUND: Triple negative (TN) tumor has a relatively high rate of recurrence and distant metastasis, but results of studies revealed that triple positive tumor is an independent predictor of axillary lymph node involvement. Our aim was to evaluate the frequency of nonsentinel lymph node metastasis (NSLNM) involvement in operable TN breast cancer with positive sentinel lymph node (SLN) and predicting the likelihood of NSLNM in this cohort of patients by using 4 different nomograms. METHODS: A total of 128 patients with TN and SLN(+) underwent complete axillary lymph node dissection in 14 different centers in Turkey. For comparison, we used our previous multicenter MF08-01 Protocol, which identified 441 patients with estrogen receptor (ER(+)) who had a positive SLN biopsy and underwent subsequent complete axillary lymph node dissection. Turkish, Cambridge, and Stanford nomograms and the Tenon Score system were used to calculate the probability of NSLNM. RESULTS: Patients with TN tumor had a larger tumor size. The actual percentage of NSLN positivity was 41% in the TN group and 47.1% in patient with ER(+). The Tenon Score was ≤3.5 in 12% of patients with TN and ER(+); the area under the curve in the receiver operating characteristics curve were 0.53 and 0.59, respectively. Based on the Turkish, Cambridge, and Stanford nomograms, areas under the curve were 0.54, 0.53, and 0.61, respectively in patients with TN, and were 0.79, 0.72, and 0.70, respectively, in patients with ER(+). CONCLUSION: Using the Tenon Score system underestimates NSLN positivity, and tested nomograms are not good discriminators of NSLNM in patients with TN and positive SLN.

Investigation of the mechanism of nicotine-induced relaxation in guinea pig gallbladder.

BACKGROUND: Muscular contraction of the gallbladder is the primary determinant of bile delivery into duedonum. Gallbladder filling and emptying are influenced by both inhibitory and excitatory stimuli, and NO plays a key role in normal relaxation. In this study, to determine whether nicotine acts on the gallbladder muscle, the mechanism of its effect on strips of guinea pig gallbladder was studied in vitro. MATERIALS AND METHODS: Guinea pig gallbladder muscle strips were mounted in organ bath with modified Krebs-Henseleit solution and aerated with Carbogen. Tension was measured with isometric force transducers, and muscle relaxation was expressed as percent decrease of precontraction induced by carbachol. RESULTS: Nicotine produced concentration dependent relaxation when preparations were precontracted by carbachol (10(-6) M). Nicotine-induced relaxation was 51.6 +/- 3.2% of phenylephrine contraction and was not affected by guanethidine (10(-5) M), propranolol (10(-6) M), hexamethonium (10(-4) M), indomethacin (10(-5) M), N(w)-nitro L-arginine methyl ester (L-NAME) (3 x 10(-5) M), methylene blue (10(-5) M), glibenclamide (10(-5) M), clotrimazole (10(-6) M), tetraethylammonium (3 x 10(-4) M), or 4-aminopyridine (10(-3) M). Nicotine did not exhibit a calcium antagonizing effect. CONCLUSIONS: From these results, we concluded that nicotine-induced relaxation of the guinea pig gallbladder is not mediated by the release of noradrenaline, nitric oxide (NO), prostaglandins, or a related substance, or by the activation of potassium channels, or by the stimulation of nicotinic cholinoceptors. Further work is needed to determine the cellular mechanism(s) of action by which nicotine acts on gallbladder smooth muscle.

Polymorphisms in the MTHFR gene are associated with breast cancer.

The methylenetetrahydrofolate reductase (MTHFR) gene is a polymorphic gene involved in folate metabolism, DNA biosynthesis, methylation and genomic integrity in actively dividing cells. The MTHFR C677T and A1298C polymorphisms are likely to play an important role in the susceptibility to breast cancer. In this case-control study, we examined the role of MTHFR C677T and A1298C polymorphisms in breast cancer patients. We genotyped 118 premenopausal women with sporadic breast cancer and 193 controls, using a PCR-RFLP method. The allele frequencies of the MTHFR 677T were 31.36% in the breast cancer cases and 28.76% in the controls. The allele frequencies of the MTHFR 1298C were 37.29% in the breast cancer subjects and 31.35% in the controls. Frequencies of MTHFR C677C, C677T and T677T were 50.8, 33.9 and 14.4% in the breast cancer patients and 48.7, 45.1 and 6.2% in the controls, respectively. The results of a chi(2) analysis indicated that the MTHFR 677T allele was significantly distributed (chi(2) = 7.234; p = 0.027). Likewise, the MTHFR T677T genotype showed a 2.5-fold increased risk for breast cancer and the C1298C genotype showed a 1.9-fold increased risk for breast cancer. In the compound genotypes, T677T/A1298A and C677C/C1298C showed a 4.472- and a 2.301-fold increased risk for breast cancer (OR = 4.472, p = 0.001, and OR = 2.301, p = 0.024), respectively. In conclusion, our data suggest that the MTHFR 677T, 1298C alleles, T677T, C1298C genotypes, and C677C/C1298C and T677T/A1298A compound genotypes are genetic risk factors for premenopausal women with sporadic breast cancer.