scholarly journals Germline Mutation in MUS81 Resulting in Impaired Protein Stability is Associated with Familial Breast and Thyroid Cancer

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1289
Author(s):  
Maisa Pinheiro ◽  
Fernanda Cristina Sulla Lupinacci ◽  
Karina Miranda Santiago ◽  
Sandra Aparecida Drigo ◽  
Fabio Albuquerque Marchi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Family History ◽  
Protein Stability ◽  
Positive Family History ◽  
Low Frequency ◽  
Strand Break ◽  
Healthy Population ◽  
Cellular Models ◽  
Number Of Patients ◽  
History Of

Multiple primary thyroid cancer (TC) and breast cancer (BC) are commonly diagnosed, and the lifetime risk for these cancers is increased in patients with a positive family history of both TC and BC. Although this phenotype is partially explained by TP53 or PTEN mutations, a significant number of patients are negative for these alterations. We judiciously recruited patients diagnosed with BC and/or TC having a family history of these tumors and assessed their whole-exome sequencing. After variant prioritization, we selected MUS81 c.1292G>A (p.R431H) for further investigation. This variant was genotyped in a healthy population and sporadic BC/TC tissues and investigated at the protein level and cellular models. MUS81 c.1292G>A was the most frequent variant (25%) and the strongest candidate due to its function of double-strand break repair. This variant was confirmed in four relatives from two families. MUS81 p.R431H protein exhibited lower expression levels in tumors from patients positive for the germline variant, compared with wild-type BC, and normal breast and thyroid tissues. Using cell line models, we showed that c.1292G>A induced protein instability and affected DNA damage response. We suggest that MUS81 is a novel candidate involved in familial BC/TC based on its low frequency in healthy individuals and proven effect in protein stability.

scholarly journals The association between diabetes and thyroid cancer risk: a hospital-based case-control study in China

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Meng Wang ◽  
Wei-Wei Gong ◽  
Feng Lu ◽  
Ru-Ying Hu ◽  
Qing-Fang He ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Family History ◽  
Case Control Study ◽  
Positive Family History ◽  
Case Control ◽  
Diabetes Duration ◽  
Family History Of Diabetes ◽  
Thyroid Cancer Risk ◽  
History Of ◽  
Control Study

Abstract Background Previous studies have indicated inconsistent relationships of diabetes with thyroid cancer risk, yet little is known in China. In this study, we aimed to investigate the associations between diabetes, diabetes duration and the risk of thyroid cancer in Chinese population. Methods A 1:1 matched case-control study was performed between 2015 and 2017 in Zhejiang Province including 2,937 thyroid cancer cases and 2,937 healthy controls. Odds ratios (ORs) with 95 % confidence intervals (CIs) for thyroid cancer were estimated in logistic regression models. Specific effects stratified by age, as well as sex, body mass index (BMI) and family history of diabetes were also examined. Results Overall, neither diabetes (OR = 0.75, 95 % CI: 0.21–2.73) nor diabetes duration (OR = 0.14, 95 % CI: 0.02–1.22 for diabetes duration ≦ 5 years; OR = 2.10, 95 % CI: 0.32–13.94 for diabetes duration > 5 years) was significantly associated with thyroid cancer. In stratified analyses, significant lower risk of thyroid cancer was observed among subjects with diabetes and shorter diabetes duration ( ≦ 5 years), but limited to those who were aged more than 40 years, female, overweight/obese and had positive family history of diabetes. Conclusions Diabetes and shorter diabetes duration were significantly associated with decreased risk of thyroid cancer in individuals characterized by older age, female sex, higher BMI and positive family history of diabetes.

scholarly journals P161 A comparative study of childhood-onset SLE with adult-onset patients: a single centre study

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Neil T Morton ◽  
Zoe Rutter-Locher ◽  
Maumar Durrani ◽  
Shirish Sangle ◽  
Nick Wilkinson ◽  
...  
Keyword(s):  
Family History ◽  
Renal Involvement ◽  
Positive Family History ◽  
Disease Onset ◽  
Adult Onset ◽  
Childhood Onset ◽  
Number Of Patients ◽  
Dsdna Antibody ◽  
History Of ◽  
Mixed Ethnicity

Abstract Background/Aims  Childhood-onset SLE (cSLE) was once associated with significant mortality but 5-year survival rates have now improved significantly. We retrospectively compared the clinical features and outcomes of cSLE patients with an adult-onset SLE (aSLE) group. Methods  We retrospectively studied data from 30 patients from our cSLE patients (onset before age 16) compared with 65 aSLE randomly selected in a 2:1 ratio, from our Lupus clinic patients fulfilling the 1997 ACR SLE criteria. Data regarding ethnicity, age of onset, family history, serology, complications, medications and outcomes were recorded. Results  Of cSLE patients 24 were female and 6 male (F:M ratio 4:1), with 16 patients (53%) Afro-Caribbean, 8 Caucasian, 5 Asian and 1 of mixed ethnicity. In the aSLE group, 60 patients were female and 5 male (ratio 9:1), with 29 (44%) Afro-Caribbean, 13 Asian, 21 Caucasian and 2 of mixed ethnicity. Median age at disease onset was 14 years (10-16) in cSLE and 29 years (17-50) in aSLE. A positive family history of SLE was seen in 37% (11/30) of cSLE patients compared to 11% (7/65) of aSLE [p = 0.003]. There was no difference in family history of other autoimmune rheumatic diseases (10% vs 14% [p = 0.57]). Table 1 shows frequency of different autoantibodies, with anti-dsDNA and anti-cardiolipin antibodies significantly more frequent in the cSLE group [p = 0.017, p = 0.016 respectively]. Lupus nephritis appears to be more common in cSLE but not significantly (80% renal involvement vs 69% aSLE).There was no difference between involvement of chest, haematological, VTE or APS. Standard of care treatment was used in both groups, including oral prednisolone (>80% patients), anti-malarial and immunosuppressive medications. Renal flares were significantly more frequent in cSLE (23% vs 8%, [p = 0.027]). Of those deceased, only 1 was directly due to SLE. P161 Table 1:Serological markercSLE (n = 30)aSLE (n = 65)Number of patients%Number of patients%ANA2790%6498%dsDNA23*77%33*51%ENA1447%3655%RNP827%2335%Anti-Ro1033%2132%Anti-Sm827%1218%C1Q14**64%19**63%ACL17*57%20*31%LAC930%1828%RF517%69%Comparison of serological markers.*p < 0.05 (Chi-square used).**10 patients’ data missing. Conclusion  More cSLE patients had a positive SLE family history and had higher anti-dsDNA antibody positivity compared to aSLE. Renal involvement was observed more commonly in cSLE than aSLE patients but was not statistically significant. Our results suggest that the cSLE cohort have a higher prevalence of specific lupus serology and a positive family history of SLE which may point towards more aggressive disease. Disclosure  N.T. Morton: None. Z. Rutter-Locher: None. M. Durrani: None. S. Sangle: None. N. Wilkinson: None. D. D'Cruz: None.

scholarly journals EPITHELIAL OVARIAN CANCER;

2012 ◽  
Vol 19 (01) ◽  
pp. 040-045
Author(s):  
SARAH SAEED ◽  
MOHAMMAD AKRAM
Keyword(s):  
Ovarian Cancer ◽  
Family History ◽  
Epithelial Ovarian Cancer ◽  
Positive Family History ◽  
Striking Feature ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
University Of Toronto ◽  
Number Of Patients ◽  
History Of

Background: Epithelial ovarian cancer is the most common cancer of gynaecologic origin in Pakistani women. It ranks amongthe ten most common cancers in our women. Despite being commonly encountered, information regarding the clinicopathological features islacking. Objective: To study the clinical and pathological features of epithelial ovarian cancer in our patients. Study Design: Retrospective study.Setting: Department of Medical Oncology, Jinnah Hospital Lahore. Period: Jan 01,2001 to Dec 31, 2002. Patients and methods: All patientswith histological or cytological diagnosis of epithelial ovarian cancer regardless of stage were included in the study. Information was obtainedfrom medical records which were reviewed thoroughly. Blood samples for analysis of BRCA mutations were sent to University of Toronto,Sunnybrook & Women’s College Health Sciences Centre, Toronto, Canada. Results: 75 patients were accrued. Mean age of the patients was47 years. The well defined risk factors such as nulliparity, lack of lactation, early menarche and late menopause were not present in the majorityof our patients. One striking feature was the number of patients with family history of cancer (18.7%). Majority were first degree relatives of thepatients and most had ovarian or breast cancer. BRCA1 and BRCA2 were seen in nine (12%) of the patients. Clinical presentation and histologicfeatures were similar to American and European patients, the only difference was that a large number (88%) of our patients presented withadvanced (stage III or IV) disease. Conclusions: Epithelial ovarian cancer manifests itself in a younger population of our women. Higherfrequency of positive family history was another striking feature of Pakistani patients.

Flunarizine in Migraine Prophylaxis: Predictive Factors for A Positive Response

Cephalalgia ◽  
1998 ◽  
Vol 18 (6) ◽  
pp. 349-352 ◽  
Author(s):  
C Lucetti ◽  
A Nuti ◽  
N Pavese ◽  
G Gambaccini ◽  
G Rossi ◽  
...  
Keyword(s):  
Family History ◽  
Predictive Factors ◽  
Positive Family History ◽  
Previous History ◽  
Low Frequency ◽  
Term Treatment ◽  
Migraine Prophylaxis ◽  
Long Term Treatment ◽  
History Of ◽  
Negative Factors

The efficacy of flunarizine in migraine prophylaxis is confirmed in both open and controlled trials. However, it is unknown what factors may influence a good response to prophylaxis with flunarizine. The aim of this study was to determine the possible predictive factors for therapeutic responsiveness to 3 months' treatment with flunarizine. One-hundred headache patients treated with flunarizine were evaluated. We considered “responders” those patients who recorded a reduction in migraine frequency of 75% after treatment. Statistical analysis revealed four factors which might influence therapeutic responsiveness in our patients. Positive factors were a family history ( p<0.01) and high intensity of pain ( p<0.01); negative factors were frequent attacks ( p<0.01) and a history of analgesic abuse ( p<0.001). Patients with no previous history of analgesic abuse, low frequency of attacks at baseline, higher levels of migraine pain, and positive family history constitute the prototype of flunarizine long-term treatment responders.

scholarly journals Differential expression of micro RNA-29 family in non-diabetic adults of diabetic and non-diabetic parents

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Uzair Abbas ◽  
Bushra Imdad ◽  
Sikander Adil Mughal ◽  
Israr Ahmed Baloch ◽  
Afshan Mehboob Khan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Family History ◽  
Positive Family History ◽  
Cross Sectional Study ◽  
Vital Role ◽  
Micro Rna ◽  
Cross Sectional ◽  
Family History Of Diabetes ◽  
History Of

Abstract Objective MicroRNAs are known to regulate 60% of genes at post translational level. MicroRNAs including Micro RNA-29 family play a vital role in cellular activities and have validate role in numerous metabolic disorders inclusive of diabetes mellitus and its complications. While micro RNA profile changes years before the occurrence of disease. This cross-sectional study was conducted in non-diabetic adults of diabetic and non-diabetic parents to explore the early changes in expression of micro RNA-29 family as it can be served as early biomarker of type 2 diabetes in non-diabetic adults. This study was conducted from January 2019 to January 2021. Micro RNA was extracted from plasma of 50 participants and expression was compared through qPCR. While data was analyzed through SPSS version 21.0. Results 29a and 29b had lower expression in participants with family history of DM compared to those having no family history of DM (P < 0.0001). While micro RNA 29c was found to be significantly higher in participants with positive family history of type 2 diabetes as compared to those without family history of diabetes (P = 0.001).

A Group Therapy Approach to Facilitate Integration of Risk Information for Women at Risk for Breast Cancer

1998 ◽  
Vol 43 (4) ◽  
pp. 375-380 ◽  
Author(s):  
Mary Jane Esplen ◽  
Brenda Toner ◽  
Jonathan Hunter ◽  
Gordon Glendon ◽  
Kate Butler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Family History ◽  
Group Therapy ◽  
Perceived Risk ◽  
Positive Family History ◽  
Risk Information ◽  
Degree Relative ◽  
Therapy Approach ◽  
History Of

Objective: To describe and illustrate elements of a group counselling approach designed to enhance the communication of risk information on breast cancer (BC) to women with a family history of this disease. Breast cancer is a leading cause of female cancer death. The most important risk factor for BC is a positive family history in at least 1 first-degree relative, and approximately one-third of women with BC have a family history of the disease. Recent evidence suggests that there is a significant psychological impact associated with having a family history of BC, and this may influence the psychological adjustment and response to being counselled for personal risk. New counselling approaches are required. Method: This paper describes a group therapy approach that incorporates principles of supportive-expressive therapy designed to address the emotional impact of being at risk for BC and to promote accuracy of perceived risk. The key elements of the intervention are described along with clinical illustrations from groups that are part of an ongoing study to develop and standardize the group therapy. Conclusion: Qualitative data from the groups suggest that this model of therapy is both feasible and effective.

scholarly journals Predictive Factors of Malignancy in Cytology of Indeterminate Follicular and Hürthle Cell Neoplasms of the Thyroid Gland

2019 ◽  
Vol 103 (1-2) ◽  
pp. 9-14
Author(s):  
Bahadır Öz ◽  
Serap Doğan ◽  
Ertan Emek ◽  
Muhammed Akyüz ◽  
Alper Akcan ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Family History ◽  
Radiation Exposure ◽  
Fine Needle Aspiration ◽  
Fine Needle Aspiration Biopsy ◽  
Needle Aspiration ◽  
Cytologic Diagnosis ◽  
Fine Needle ◽  
Solitary Nodule ◽  
History Of

The objective of the current study was to determine the risk of malignancy in patients with thyroid nodules with cytology of indeterminate follicular and indeterminate Hürthle cell neoplasm (HN). The cytologic diagnosis of follicular neoplasm (FN) or HN remains a diagnostic challenge. Often, surgery is recommended for such lesions. A retrospective analysis was performed on 80 patients who underwent thyroid surgery following a diagnosis of indeterminate FN and indeterminate HN in thyroid fine-needle aspiration biopsy. Sex; age; family history of thyroid cancer and radiation exposure; coexisting thyroid conditions, such as solitary nodule; multinodularity; cytologic diagnosis; sonographic features; type of surgical treatment; and histopathologic results were recorded. Of the 80 patients, 52 (65%) had FN on fine-needle aspiration biopsy cytology and 28 (35%) had HN. A total of 23 patients (28.7%) had primary thyroid cancers on surgical pathology, and 57 (71.3%) had benign diagnoses. Univariate analysis showed no differences between the benign and malignant groups by sex, nodule size, family history of thyroid cancer, history of radiation exposure, presence of solitary nodule or multinodularity in the nodular features. In multivariate binary logistic regression analysis, the factors that were statistically significant predictors of malignancy were microcalcification [odds ratio (OR), 10.9; 95% confidence interval (CI), 2.18–54.7; P = 0.004], being older than 45 years (OR, 4.2; 95% CI, 1.25–14.63; P = 0.02]. The independent predictors of malignancy in FN and HN are micorcalcification and being older than 45 years, the use of which may predict the risk of thyroid cancer.

Levels of anxiety, depression and denial in patients with myocardial infarction

1997 ◽  
Vol 12 (3) ◽  
pp. 149-151 ◽  
Author(s):  
D Sarantidis ◽  
A Thomas ◽  
K Iphantis ◽  
N Katsaros ◽  
J Tripodianakis ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Intensive Care Unit ◽  
Family History ◽  
Positive Family History ◽  
Anxiety And Depression ◽  
Previous Myocardial Infarction ◽  
History Of ◽  
Seeking Help ◽  
Anxiety Depression

SummaryIn this study we investigated 1) the changes in anxiety, depression and denial from admission to discharge in patients admitted to the intensive care unit following an acute myocardial infarction and 2) the effect of smoking habits, time lapsed from the appearance of symptoms to seeking help behavior, presence of a person that motivated the patient to seek help, previous myocardial infarction (MI) and family history of MI, on these changes. The results indicated that 1) the levels of both anxiety and depression increased from admission to discharge, while denial decreased; 2) positive family history of MI was associated with lower difference of denial between admission and discharge.

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