ABSTRACT
BACKGROUND: Breast cancer (BC) is the most common type of cancer in women. Among many risk factors of BC, mutations in BRCA2 gene were found to be the primary cause in 5-10% of cases. The majority of deleterious mutations are frameshift or nonsense mutations. Most of the reported BRCA2 mutations are protein truncating mutations. METHODS: The study aimed to describe the pattern of mutations including single nucleotide polymorphisms (SNPs) and variants of the BRCA2 (exon11) gene among Sudanese women patients diagnosed with BC. In this study a specific region of BRCA2 exon 11 was targeted using PCR and DNA sequencing. RESULTS: Early onset cases 25/45 (55.6%) were premenopausal women with a mean age of 36.6 years. Multiparity was more frequent within the study amounting to 30 cases (66.6%), with a mean parity of 4.1. Ductal type tumor was the predominant type detected in 22 cases (48.8%) among the reported histotypes. A heterozygous monoallelic nonsense mutation at nucleotide 3385 was found in four patients out of 9, where TTA codon was converted into the stop codon TGA. CONCLUSION: This study detected a monoallelic nonsense mutation in four Sudanese female patients diagnosed with early onset BC from different families. Further work is needed to demonstrate its usefulness in screening of BC.
Subject(s)
Alleles , BRCA2 Protein/genetics , Breast Neoplasms/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Aged, 80 and over , Amino Acid Sequence , Base Sequence , Case-Control Studies , Codon, Nonsense , Exons , Female , Heterozygote , Humans , Middle Aged , Premenopause , Sequence Analysis, DNA , Sudan/epidemiologyABSTRACT
OBJECTIVES: We aimed to stratify the possible risk factors for diabetic cardiac autonomic neuropathy (CAN). METHODS: We did a meta-analysis of risk factors of CAN. We did a web-based search for literature in MEDLINE/PubMed, Scopus database and CENTRAL database up to August 2015. We included clinical trials or cohort studies that provide data about relationship between CAN and variables of interest. Our risk factors of interest were age, sex, duration of diabetes, body mass index (BMI), systolic blood pressure (sBP) and diastolic blood pressure (dBP), glycated haemoglobin (HbA1c), high-density lipoprotein and low-density lipoprotein (HDL and LDL), triglycerides, retinopathy and nephropathy. We generated Forest plots, χ2 test and I2 as tests for heterogeneity, risk ratio (RR), mean difference (MD), CIs and p values by ReVMan V.5.3 software. RESULTS: We found a total of 882 related items. We excluded 873 studies from the title and abstract and 4 studies after review of full reports. Four studies were included. Our meta-analysis showed significant association between CAN and age (MD=4.94 (3.46 to 6.42)), duration of diabetes (MD=4.51 (2.51 to 6.52)), HbA1c (MD=0.48 (0.28 to 0.67)), BMI (MD=0.55 (0.08 to 1.01)), serum triglycerides (MD=0.09 (0.01 to 0.17)), proliferative retinopathy (RR=3.69 (1.20 to 11.34)), microalbuminuria (RR=2.47 (1.43 to 4.29)), hypertension (RR=4.18 (2.52 to 6.91)) and sBP (MD=4.10 (2.20 to 6.00)). We neither discovered the absence of significant association between the development of CAN and male sex (RR=1.57 (0.45 to 5.39)), dBP (MD=0.89 (-0.36 to 2.14)), cholesterol level (MD=1.19 (-0.99 to 3.36)), LDL (MD=0.12 (-0.15 to 0.39)), nor HDL level (MD=-0.28 (-0.58 to 0.03)). CONCLUSIONS: Age, duration of diabetes, HbA1c, BMI, serum triglycerides, proliferative retinopathy, microalbuminuria, hypertension and sBP are directly related to the risk of development of diabetic CAN.
