scholarly journals BRAF mutation testing of MSI CRCs in Lynch syndrome diagnostics: performance and efficiency according to patient’s age

2019 ◽  
Author(s):  
Hendrik Bläker ◽  
Saskia Haupt ◽  
Monika Morak ◽  
Elke Holinski-Feder ◽  
Alexander Arnold ◽  
...  

AbstractBackground and aimsBRAF V600E mutations have been reported to be associated with sporadic microsatellite-unstable (MSI) colorectal cancer (CRC), while rarely detected in CRCs of Lynch syndrome (LS) patients. Therefore, current international diagnostic guidelines recommend somatic BRAF mutation testing in MLH1-deficient MSI CRC patients to exclude LS. As sporadic BRAF-mutant MSI CRC is a disease of the elderly, while LS-associated CRC usually occurs at younger age, we hypothesized that the efficacy of BRAF testing in LS diagnostics may be age-dependent.MethodsWe systematically compared the prevalence of BRAF V600E mutations in LS-associated CRCs and MSI CRCs from population-based cohorts in different age groups as available from published studies, databases, and population-based patient cohorts. Cost calculations and sensitivity analysis of the BRAF testing for exclusion of LS was performed.ResultsAmong 969 MSI CRCs from LS mutation carriers from the literature and German HNPCC Consortium, 15 (1.6%, 95% CI: 0.9-2.6%) harbored BRAF mutations. 6/7 LS patients with BRAF-mutant CRC and reported age were <50 years. Among unselected MSI CRCs, 44.8% (339/756) harbored BRAF mutations, 92.3% (313/339) of which were detected in patients >60 years. In MSI CRC patients <50, BRAF mutations were detected only in 0.6% (2/339), and the inclusion of BRAF testing led to increased costs and higher risk of missing LS patients (1.2%) compared to other age groups.ConclusionBRAF testing in patients <50 years is cost-inefficient and carries the highest risk of missing LS patients among different age groups. We suggest direct referral of MSI CRC patients <50 years to genetic counseling without prior BRAF testing.

2013 ◽  
Vol 71 (11) ◽  
pp. 841-845 ◽  
Author(s):  
Gabriel Alcala-Cerra ◽  
Adam M.H. Young ◽  
Angel Paternina-Caicedo ◽  
Eduardo Santamaria Carvalhal Ribas

Objective To assess trends in mortality from 1999 to 2008 resulting from non-traumatic subarachnoid hemorrhage (SAH) in the Colombian population. Method This population-based study analyzed all deaths by assuming a Poisson model. Results Subarachnoid hemorrhage-related deaths showed a statistically significant increase of 1.6% per year (p<0.001). The age-standardized analysis demonstrated an increased mortality trend of 3.3% per year (p<0.001) in people older than 70 years, but a decreased mortality trend in people younger than 50. It remained stable in patients 50-69 years old. Conclusion The overall SAH-related mortality rate in Colombia has increased because increased mortality among the elderly has been counterbalanced by reduced mortality rates in younger age groups. These disparities may reflect epidemiologic transition, treatment inequities, or a less favorable comorbid profile.


Author(s):  
Timothy Gustavo Cavazzotto ◽  
Natã Gomes de Lima Stavinski ◽  
Marcos Roberto Queiroga ◽  
Michael Pereira da Silva ◽  
Edilson Serpeloni Cyrino ◽  
...  

Marital status mediates an association between physical activity (PA) and TV time with health outcomes. However, population-based studies have revealed that the health effect of marriage or divorce is age-dependent and differs between women and men. The study aimed to identify the age and sex-related associations between marital status with PA and TV time. We used data from Vigitel, an annual telephone survey started in 2006 in Brazil. We applied a complex sample logistic regression model to estimate the odds for PA and TV time comparing marital statuses according to age and sex subgroups, independent of obesity, hypertension, diabetes, self-assessed poor health, and smoking. Our sample included 561,837 individuals from 18 to 99 years, with a TV time > 3 h/day (prevalence = 25.2%) and PA > 150 min/week (prevalence = 35%). Later, we divided our sample in seven age groups by marital status and sex. Compared to single individuals, married men and women were less likely to watch TV more than 3 h/day in participants >30 years old. When compared to single, married participants were less likely to do more than 150 min of PA/week at younger age groups. Married women older than 40 years were more likely to do more than 150 min of PA/week than the single ones, while there were no differences among married men by age group. In conclusion, our study suggests that the investments in public policies to encourage the practice of PA and reduction of TV time could be based on the marital status, sex, and age, prioritizing less active groups.


2008 ◽  
Vol 31 (4) ◽  
pp. 12
Author(s):  
A J Hyde ◽  
D Fontaine ◽  
R C Green ◽  
M Simms ◽  
P S Parfrey ◽  
...  

Background: Lynch Syndrome is an autosomal dominant trait that accounts forapproximately 3% of all cases of colorectal cancer (CRC). It is caused by mutations in DNA mismatch repair (MMR) genes, most commonly MLH1 or MSH2. These MMR defects cause high levels of microsatellite instability (MSI-H) in the tumours. MSI testing of all CRCs to identify potential Lynch Syndrome cases is not practical, so the Bethesda Guidelines, which use clinical and pathological features, were created to identify those tumours most likely to be MSI-H^1. In 2007 Jenkins et. al. created MsPath, a tool based on the pathological features described in the rarely used 3^rd Bethesda criterion, to improve prediction of MSI-H tumours among CRC cases diagnosed before age 60 years^2. Methods: We collected a population-based cohort of 716 CRC cases diagnosed before age 75 years in Newfoundland. For each of these cases we collected family history, performed MSI analysis, and scored a number of pathological features for the purpose of evaluating the accuracy of the Bethesda Criteria and MsPath at predicting MSI-H tumours. Results: Our work validates the MsPath tool in the Newfoundland population for the same age group used to create the tool. We found it identified MSI-H cases with a sensitivity of 95% and specificity of 35% in our population of CRCcases diagnosed before age 60 years (n=290). We also tested this tool on our older population of CRCcases, diagnosed at ages 60 to 74 years (n=426). We found it to be at least as predictive in this population,with a sensitivity of 95% and a specificity of 42%. We then used our entire cohort (N=716) to compare MsPath with the other Bethesda criteria.Bethesda criteria 1, 2, 4 and 5 together predicted MSI-H cases with a sensitivity of 67% and a specificity of 51%. MsPath was better at identifying these cases, with a sensitivity of 95% and a specificity of 39%. Conclusions: We conclude that MsPath can be extended to include patients diagnosed with CRC before age 75 years. As well, we have found that MsPath is a better predictive tool than the Revised Bethesda Guidelines for identifying MSI-H cases within a population-based setting of colorectal cancer. References: 1. Umar, A. et. al. J Natl Cancer Inst 2004;96:261-8 2.Jenkins, M.A. et. al. Gastroenterology 2007;133:48-56


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Vidya Lakshmi Purushothaman ◽  
Raphael E. Cuomo ◽  
Cedric F. Garland ◽  
Timothy K. Mackey

Abstract Background Vitamin D has been identified as a potential protective factor in the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally. Methods In this ecological study, a series of linear and polynomial regression tests were performed between country-specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps. Results The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates. Conclusion The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population-wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Aiko Maeda ◽  
Kenzo Araki ◽  
Chiaki Yamada ◽  
Shoko Nakayama ◽  
Kazuhiro Shirozu ◽  
...  

Abstract Background Hyperactive dysfunction syndrome (HDS) refers to a constellation of symptoms developing from cranial nerve overactivity caused by neurovascular compression at the root entry or exit zone near the brainstem. Although the combined features of HDS are seen in the elderly, there are no reports of such cases in adolescents, to date. Case presentation A 17-year-old male was diagnosed with right glossopharyngeal neuralgia and treated with microvascular decompression. He experienced new-onset right facial pain later and was diagnosed with right trigeminal neuralgia, which required prompt radiofrequency thermocoagulation of the right mandibular nerve. Follow-up in the third post-treatment year revealed the absence of symptom recurrence. Discussion We report the treatment of a rare case of adolescent-onset combined HDS presenting as trigeminal and glossopharyngeal neuralgia. This report highlights the possibility of combined hyperactive dysfunction syndrome in younger age groups. It is crucial to establish a diagnosis early on for prompt management.


Neurosurgery ◽  
1984 ◽  
Vol 15 (3) ◽  
pp. 318-324 ◽  
Author(s):  
Evan Lloyd Nelson ◽  
Joseph L. Melton ◽  
John F. Annegers ◽  
Edward R. Laws ◽  
Kenneth P. Offord

Abstract Between 1935 and 1974, 3598 episodes of head trauma among Olmsted County, Minnesota, residents resulted in 1097 skull fractures. Of these, 53% were simple, 16% were depressed, 12% were compound, and 19% were basilar. The age- and sex-adjusted incidence of skull fractures was 44.3 per 100,000 person-years overall, was somewhat greater in the urban than in the rural areas of Olmsted County, and was relatively stable for the final 30 years of the study. Age-specific incidence rates were highest for the very young, and simple linear fractures were the predominant type of skull fracture in this age group and among the elderly. The male:female ratio of incidence rates varied from 2.1:1 to 4.5:1 depending on fracture type. Motor vehicle accidents accounted for 38% of the skull fractures and were a particularly important cause among young males. Falls accounted for 37% of the skull fractures and were the major cause of fractures in the elderly and pediatric age groups. The results of this population-based study may be helpful in formulating recommendations for the evaluation and management of head-injured patients.


2013 ◽  
Vol 16 (4) ◽  
pp. 930-942 ◽  
Author(s):  
Ione Jayce Ceola Schneider ◽  
Marui Weber Corseuil ◽  
Antonio Fernando Boing ◽  
Eleonora d'Orsi

The purpose of this paper is to describe the knowledge about mammography and to identify associated factors in female adults and elderly. Data were obtained from two population surveys, one with female adults and another with elderly women from Florianópolis (SC) in 2009 - 2010. A descriptive analysis of the variables was carried out, the appropriate mean of responses about mammography was estimated and crude and adjusted Poisson regression was conducted to identify associated factors. Among adults, 23.1% answered all of the questions appropriately and the appropriate average responses was 7.2 (95%CI 7.1 - 7.3) in a total of 9. In the adjusted model, older age, higher education and income were associated with knowledge about mammography. For the elderly, 15.3% answered all questions appropriately and the average of appropriate responses was 6.4 (95%CI 5.2 - 6.5) and the factors associated with knowledge about mammography in the adjusted model were younger age groups, increased education and income, and identification of mammography as the main diagnostic method for breast cancer. Information about mammography can neither be transmitted in a clear way nor be easily understood; there are also demographic and socioeconomic differences concerning the knowledge about the exam.


2020 ◽  
Vol 147 (10) ◽  
pp. 2801-2810 ◽  
Author(s):  
Hendrik Bläker ◽  
Saskia Haupt ◽  
Monika Morak ◽  
Elke Holinski‐Feder ◽  
Alexander Arnold ◽  
...  

Author(s):  
Jinkyung Choi

Dietary supplements (DSs) are typically used by the elderly in a population, but younger age groups are increasingly purchasing these products. In consideration of this issue, the present study investigated the DS-related behaviors and general lifestyles of university students in South Korea. The health conditions, consciousness, involvement, and knowledge, as well as the future behavioral intentions, of DS users and non-users were determined and compared. A survey was administered to the respondents, and measurements were adapted and rephrased to suit the Korean context. Results showed that although the behaviors of DS users and non-users were characterized by similar patterns, significant differences in health involvement and future purchase were found between these groups. Health involvement influenced DSs buying intentions in the future, but no significant differences in the other variables were found. The findings suggested that university students take DSs regardless of their expectations about their efficacy and that their knowledge does not affect their intention to purchase such products.


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