scholarly journals ‘BRCA1’ RESPONSIVENESS TOWARDS BREAST CANCER-A POPULATION-WISE PHARMACOGENOMIC ANALYSIS

Author(s):  
Preethi M. Iyer ◽  
Sanjay Kumar P. ◽  
Karthikeyan S. ◽  
P. K Krishnan Namboori

<p><strong>Objective: </strong>In the present pharmacogenomic work, the genetic, epigenetic and environmental factors associated with BRCA1 induced breast cancer, cancer proneness and its variants across different populations like Indian, Netherland, Belgium, Denmark, Austrian, New Zealand, Sweden, Malaysian and Norwegian and the ‘mutation and methylation-prone’ region of BRCA1 have been computed.</p><p><strong>Methods: </strong>The global variations associated with the disease have been identified from the ‘Leiden open variation database (LOVD 3.0)’ and ‘Indian genome variation database (IGVDB)’. The variants, ‘single nucleotide polymorphisms (SNPs)’ are then characterized. The epigenetic factors associated with breast cancer have been identified from the clinical reports and further scrutinized using EpiGRAPH tool. The various contributing environmental factors responsible for the variations have been considered.</p><p><strong>Results: </strong>All the variants across different populations such as Indian, Netherland, Belgium, Denmark, Austrian, New Zealand, Sweden, Malaysian and Norwegian are found to be in a specific transcript of BRCA1 that ranges within 41,196,312-41,277,500 (81,189 base pairs) of the chromosome 17. Two ‘single nucleotide variations (SNVs)’ (5266dupC: rs397507246 and 68_69delAG: rs386833395) have been identified as risk factors in hereditary breast and ovarian cancer syndrome in the global population and 39 SNPs have been identified as pathogenic and deleterious. ‘Evolutionary history’ seems to be the most significant attribute in the predictability of methylation of BRCA1. Unhealthy dietary habits, obesity, use of unsafe cosmetics, estrogen exposure, ‘hormone replacement therapy (HRT)’, use of oral contraceptives and smoking are the major environmental risk factors associated with breast cancer incidence.</p><p><strong>Conclusion: </strong>This chromosome location (41,196,312-41,277,500 (81,189 base pairs)) can be considered as the population-specific sensitive region corresponding to BRCA1 mutation. This supports the fact that stabilization within the region can be a promising technique to control the epigenetic variants associated with the global position. The global variation in the proneness of the disease may be due to a cumulative effect of genetic, epigenetic and environmental factors subject to further experimentations with identical variations and populations. </p>

Public Health ◽  
2015 ◽  
Vol 129 (5) ◽  
pp. 549-554 ◽  
Author(s):  
S.A. Seneviratne ◽  
I.D. Campbell ◽  
N. Scott ◽  
R.A. Lawrenson ◽  
R. Shirley ◽  
...  

2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.


Author(s):  
George Koulaouzidis ◽  
Amanda E. Yung ◽  
Diana E. Yung ◽  
Karolina Skonieczna-Żydecka ◽  
Wojciech Marlicz ◽  
...  

2021 ◽  
pp. bjophthalmol-2020-317547
Author(s):  
Alex Ferdi ◽  
Vuong Nguyen ◽  
Himal Kandel ◽  
Jeremy C K Tan ◽  
Francisco Arnalich-Montiel ◽  
...  

AimsWe set out to identify risk factors for progression in untreated keratoconus patients from 34 centres across Australia, New Zealand, Spain and Italy.MethodsPatients were divided into ‘progressors’ and ‘stable’ patients for each clinical parameter: visual acuity (VA), steepest keratometry (maximum keratometry (Max-K)) and thinnest corneal thickness (TCT). Primary outcomes were the proportion of eyes with sustained progression in VA, Max-K or TCT within 3 years. Secondary outcomes included predictors of progression.ResultsThere were 3994 untreated eyes from 2283 patients. The proportion of eyes with VA, Max-K and TCT progression at 1 year were 3.2%, 6.6% and 3.1% respectively. Factors associated with VA loss were higher baseline VA (HR 1.15 per logMAR line increase in VA; p<0.001) and steeper baseline Max-K (HR 1.07 per 1D increase; p<0.001). Younger baseline age was associated with Max-K steepening (HR 0.96 per year older; p=0.001). Thicker baseline TCT, steeper baseline Max-K and younger baseline age were associated with TCT thinning: (HR 1.08 per 10 µm increase in TCT; p<0.001), (HR 1.03 per 1D increase; p=0.02) and (HR 0.98 per year younger; p=0.01), respectively.ConclusionsSteeper Max-K and younger age were the most clinically useful baseline predictors of progression as they were associated with worsening of two clinical parameters. Every 1D steeper Max-K was associated with a 7% and 3% greater risk of worsening VA and thinning TCT, respectively. Each 1 year younger was associated with a 4% and 2% greater risk of steepening Max-K and thinning TCT, respectively.


2021 ◽  
Author(s):  
Parth Sharma ◽  
Josh Thomas Georgy ◽  
Anand George Andrews ◽  
Ajoy Oommen John ◽  
Anjana Joel ◽  
...  

Abstract Purpose: Dose dense chemotherapy improves survival but also increases toxicity and treatment related cost. Here we report the prevalence of anemia, understand the risk factors of chemotherapy related anemia and determine the cost and time-delay associated with transfusion requirement in Indian non-metastatic breast cancer patients on dose dense preoperative chemotherapy.Methods: In this study, 116 triple negative breast cancer (TNBC) patients were treated preoperatively with Docetaxel and Cyclophosphamide alternating with Epirubicin and Cisplatin every 2-weekly. Patients were evaluated for anemia pre- and post-chemotherapy. We examined trends in the cell counts, transfusion requirement, time to transfusion as well as risk factors associated with transfusion during treatment, along with delay in treatment due to anemia and the additional cost incurred.Results: One hundred and sixteen women with high-risk non-metastatic TNBC were treated. Median age was 44.5 years. 56.1% had stage III disease. Delivery of 6/8 planned doses was achieved in 98.3% of patients, and all 8 doses in 86% patients. Anemia was detected at baseline in 54(46.5%) patients with mild(10-12g/dl) anemia in 42(36.2%) patients and moderate(8-10g/dl) in 12(10.3%) patients. Forty-four patients (37.9%) required transfusion during chemotherapy with 55(47.4%) patients having grade 1-2 anemia and 40(34.5%) patients having grade 3 anemia. The factors associated with transfusion were low grade of tumor (OR 2.48 (95% CI 1.08 - 5.68), p = 0.025), hemoglobin post 2 cycles of chemotherapy (OR 1.74 (95% CI 1.21- 2.51), p = 0.003), thrombocytopenia grade 3 or 4 (OR 4.35 (95% CI 1.062-17.827), p = 0.034) and drop in hemoglobin after 2 cycles (OR 1.65 (95% CI 1.09-2.48), p = 0.017). Nearly one fourth of the study population had a delay between two cycles of chemotherapy due to anemia. A median additional cost of Rs 7000 (IQR-Rs 7000 – Rs 14000) was incurred on transfusion.Conclusion: Anemia is a common toxicity associated with dose dense chemotherapy during curative breast cancer treatment leading to delay in treatment and increased cost. Low grade tumor, grade 3 or 4 thrombocytopenia and Grade 2 or higher anemia after 2 cycles of chemotherapy are risk factors for blood transfusions during treatment.


2012 ◽  
Vol 119 ◽  
pp. S621-S621
Author(s):  
G. Vega-Malagón ◽  
A.J. Vega-Malagón ◽  
A. Becerril-Santos ◽  
J.A. Rodriguez-Mendez ◽  
H.L. Hernandez-Montiel ◽  
...  

Author(s):  
Hai Minh Vu ◽  
Long Hoang Nguyen ◽  
Huong Lan Thi Nguyen ◽  
Giang Thu Vu ◽  
Cuong Tat Nguyen ◽  
...  

Falls and recurrent falls cause great health and social consequences in older people. However, these problems are poorly understood in Vietnam. A cross-sectional study was performed at seven hospitals in Thai Binh province, Vietnam, to investigate the individual and environmental factors associated with recurrent falls among elderly patients hospitalized due to fall injuries in Vietnam. A history of recurrent falls within the last 12 months, sociodemographic, health, and clinical characteristics, as well as environmental conditions, were obtained via self-reported interviews. Multivariate logistic and Poisson regression models were used to identify associated factors. Overall, the mean fall episodes in the last 12 months were 1.8 (Standard deviation—SD = 1.2) episodes, and the 12-month prevalence of recurrent falls was 40.5%. The individual risk factors included not receiving fall prevention guidelines, walking with devices, loss of sensation in hand or foot, and using pain relief medications. The environmental risk factors comprised having too-high stairs and not having dry, clean, and nonslippery bathrooms. This study highlights a significantly high 12-month prevalence of recurrent falls in older patients hospitalized after falls in Vietnam. Moreover, regular assessments of functional disabilities and hazardous environmental conditions, as well as the provision of prevention programs, have potential to prevent falls and recurrent falls.


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