BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast cancer patients

To date, BRCA1 and BRCA2 mutations in breast and/or ovarian patients have not been characterized in the Turkish population. We investigated the presence of BRCA mutations in 53 individuals with a personal and family history of breast and/or ovarian cancer, and 52 individuals with a personal history of breast cancer diagnosed below age 50 without additional family history. We have identified 11 mutations (nine BRCA1 and two BRCA2) using combined techniques involving protein truncation test, direct sequencing and heteroduplex analysis. We found eight out of 53 patients (15.1%) with a family history to carry BRCA gene mutations (seven BRCA1 and one BRCA2). Of these, four were found in 43 families presenting only breast cancer histories, and four were found in families presenting ovarian cancer with or without breast cancer. We also demonstrated two BRCA1 and one BRCA2 mutations in three out of 52 (5.8%) early-onset breast cancer cases without additional family history. Three of nine BRCA1 and both BRCA2 mutations detected in this study were not reported previously. These mutations may be specific to the Turkish population. The BRCA1 5382insC mutation, specific to Ashkenazi and Russian populations, was found twice in our study group, representing a possible founder mutation in the Turkish population. © 2000 Cancer Research Campaig

The Dilemma of the Dilated Main Pancreatic Duct in the Distal Pancreatic Remnant After Proximal Pancreatectomy for IPMN

Objective(s) A dilated main pancreatic duct in the distal remnant after proximal pancreatectomy for intraductal papillary mucinous neoplasms (IPMN) poses a diagnostic dilemma. We sought to determine parameters predictive of remnant main-duct IPMN and malignancy during surveillance. Methods Three hundred seventeen patients underwent proximal pancreatectomy for IPMN (Indiana University, 1991–2016). Main-duct dilation included those ≥ 5 mm or “dilated” on radiographic reports. Statistics compared groups using Student’s T/Mann-Whitney U tests for continuous variables or chi-square/Fisher’s exact test for categorical variables with P < 0.05 considered significant. Results High-grade/invasive IPMN or adenocarcinoma at proximal pancreatectomy predicted malignant outcomes (100.0% malignant outcomes; P < 0.001) in remnant surveillance. Low/moderate-grade lesions revealed benign outcomes at last surveillance regardless of duct diameter. Twenty of 21 patients undergoing distal remnant reoperation had a dilated main duct. Seven had main-duct IPMN on remnant pathology; these patients had greater mean maximum main-duct diameter prior to reoperation (9.5 vs 6.2 mm, P = 0.072), but this did not reach statistical significance. Several features showed high sensitivity/specificity for remnant main-duct IPMN. Conclusions Remnant main-duct dilation after proximal pancreatectomy for IPMN remains a diagnostic dilemma. Several parameters show a promise in accurately diagnosing main-duct IPMN in the remnant

Financial market development, global financial crisis and economic growth : evidence from developing nations

Emerging and frontier markets in Africa have witnessed various economic and financial reforms aimed at integrating the domestic markets into the global financial market to attract investment. Whether these reforms promote high economic growth remains inconclusive. The paper applies the pooled mean group estimation technique to empirically re-investigate the link between financial market development, global financial crisis, and economic growth in selected African economies. The results strongly support our hypotheses that stock market and banking sector development promotes economic growth in the selected countries. Moreover, financial crisis reduce the positive effects of both the stock market and banking sector developments on economic growth. The study suggests that both the banking sector and stock market are important to deliver the long-run economic growth that the African region desired. Moreover, effort should be made to enact policy measures that would ensure development of the stock market which has received inadequate attention.info:eu-repo/semantics/publishedVersio

Combined effect of CCND1 and COMT polymorphisms and increased breast cancer risk

<p>Abstract</p> <p>Background</p> <p>Estrogens are crucial tumorigenic hormones, which impact the cell growth and proliferation during breast cancer development. Estrogens are metabolized by a series of enzymes including COMT, which converts catechol estrogens into biologically non-hazardous methoxyestrogens. Several studies have also shown the relationship between estrogen and cell cycle progression through activation of CCND1 transcription.</p> <p>Methods</p> <p>In this study, we have investigated the independent and the combined effects of commonly occurring CCND1 (Pro241Pro, A870G) and COMT (Met108/158Val) polymorphisms to breast cancer risk in two independent Caucasian populations from Ontario (1228 breast cancer cases and 719 population controls) and Finland (728 breast cancer cases and 687 population controls). Both COMT and CCND1 polymorphisms have been previously shown to impact on the enzymatic activity of the coded proteins.</p> <p>Results</p> <p>Here, we have shown that the high enzymatic activity genotype of CCND1^High(AA) was associated with increased breast cancer risk in both the Ontario [OR: 1.3, 95%CI (1.0–1.69)] and the Finland sample [OR: 1.4, 95%CI (1.01–1.84)]. The heterozygous COMT^Medium(MetVal) and the high enzymatic activity of COMT^High(ValVal) genotype was also associated with breast cancer risk in Ontario cases, [OR: 1.3, 95%CI (1.07–1.68)] and [OR: 1.4, 95%CI (1.07–1.81)], respectively. However, there was neither a statistically significant association nor increased trend of breast cancer risk with COMT^High(ValVal) genotypes in the Finland cases [OR: 1.0, 95%CI (0.73–1.39)]. In the combined analysis, the higher activity alleles of the COMT and CCND1 is associated with increased breast cancer risk in both Ontario [OR: <b>2.22</b>, 95%CI (1.49–3.28)] and Finland [OR: <b>1.73</b>, 95%CI (1.08–2.78)] populations studied. The trend test was statistically significant in both the Ontario and Finland populations across the genotypes associated with increasing enzymatic activity.</p> <p>Conclusion</p> <p>Using two independent Caucasian populations, we have shown a stronger combined effect of the two commonly occurring CCND1 and COMT genotypes in the context of breast cancer predisposition.</p

Hereditary breast cancer in Middle Eastern and North African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population

Germ-line mutations in BRCA1 breast cancer susceptibility gene account for a large proportion of hereditary breast cancer families and show considerable ethnic and geographical variations. The contribution of BRCA1 mutations to hereditary breast cancer has not yet been thoroughly investigated in Middle Eastern and North African populations. In this study, 16 Tunisian high-risk breast cancer families were screened for germline mutations in the entire BRCA1 coding region and exon–intron boundaries using direct sequencing. Six families were found to carry BRCA1 mutations with a prevalence of 37.5%. Four different deleterious mutations were detected. Three truncating mutations were previously described: c.798_799delTT (916 delTT), c.3331_3334delCAAG (3450 delCAAG), c.5266dupC (5382 insC) and one splice site mutation which seems to be specific to the Tunisian population: c.212 + 2insG (IVS5 + 2insG). We also identified 15 variants of unknown clinical significance. The c.798_799delTT mutation occurred at an 18% frequency and was shared by three apparently unrelated families. Analyzing five microsatellite markers in and flanking the BRCA1 locus showed a common haplotype associated with this mutation. This suggests that the c.798_799delTT mutation is a Tunisian founder mutation. Our findings indicate that the Tunisian population has a spectrum of prevalent BRCA1 mutations, some of which appear as recurrent and founding mutations

Estrogen receptor codon 594 and HER2 codon 655 polymorphisms and breast cancer risk

The estrogen receptor (ER) and the human epithelial growth factor receptor 2 (HER2) genes have been implicated in the development and prognosis of breast cancer. Several genetic polymorphic sites in these genes have been identified and associated with the risk of breast cancer. We have investigated the association between the estrogen receptor codon 594 (ACA to ACG) and HER2 codon 655 (ATC to GTC) polymorphisms and breast cancer risk. Genomic DNA from breast cancer patients and control subjects was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-R-FLP). When allelic frequencies of the ER codon 594 and HER2 codon 655 gene were compared, no significant differences were observed between the patient and control groups. (P = 0.063, OR = 1.55, 95% CI = 0.25-9.41 and P = 0.949, OR = 1.01, 95% CI = 0.55-1.88, respectively). In conclusion, our results support the view that both the ER codon 594 and HER2 codon 655 polymorphisms are not associated with increased risk of breast cancer. (C) 2003 Elsevier Inc. All rights reserved