Characterisation of Familial Colorectal Cancer Type X, Lynch syndrome and non-familial colorectal cancer

Background:Familial Colorectal Cancer Type X (FCCTX) is defined as individuals with colorectal cancer (CRC) who families meet Amsterdam Criteria-1 (AC1), but whose tumours are DNA-mismatch-repair-proficient, unlike Lynch syndrome (LS). FCCTX does not have an increased risk of extra-colonic cancers. This analysis compares epidemiologic and clinicopathologic features among FCCTX, LS, and ‘non-familial' (non-AC1) CRC cases.Methods:From the Colon Cancer Family Registry, FCCTX (n=173), LS (n=303), and non-AC1 (n=9603) CRC cases were identified. Questionnaire-based epidemiologic information and CRC pathologic features were compared across case groups using polytomous logistic regression.Results:Compared with LS, FCCTX cases were less likely to be current (vs never) smokers; have a proximal subsite (vs rectal) tumour; or have mucinous histology, poor differentiation, or tumour-infiltrating lymphocytes. There were no observed differences in co-morbidities or medication usage.Conclusions:FCCTX were less likely to be current tobacco users; other exposures were similar between these groups. Histopathologic differences highly suggestive of LS CRCs do not appear to be shared by FCCTX

High frequency of pathogenic non-founder germline mutations in BRCA1 and BRCA2 in families with breast and ovarian cancer in a founder population

Funding Information: This work was supported by State Research Program “Biomedicine for the public health (BIOMEDICINE)” project 5 “Personalised cancer diagnostics and treatment effectiveness evaluation”. Publisher Copyright: © 2018 The Author(s).Background: Pathogenic BRCA1 founder mutations (c.4035delA, c.5266dupC) contribute to 3.77% of all consecutive primary breast cancers and 9.9% of all consecutive primary ovarian cancers. Identifying germline pathogenic gene variants in patients with primary breast and ovarian cancer could significantly impact the medical management of patients. The aim of the study was to evaluate the rate of pathogenic mutations in the 26 breast and ovarian cancer susceptibility genes in patients who meet the criteria for BRCA1/2 testing and to compare the accuracy of different selection criteria for second-line testing in a founder population. Methods: Fifteen female probands and 1 male proband that met National Comprehensive Cancer Network (NCCN) criteria for BRCA1/2 testing were included in the study and underwent 26-gene panel testing. Fourteen probands had breast cancer, one proband had ovarian cancer, and one proband had both breast and ovarian cancer. In a 26-gene panel, the following breast and/or ovarian cancer susceptibility genes were included: ATM, BARD1, BLM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FAM175A, MEN1, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53, and XRCC2. All patients previously tested negative for BRCA1 founder mutations. Results: In 44% (7 out of 16) of tested probands, pathogenic mutations were identified. Six probands carried pathogenic mutations in BRCA1, and one proband carried pathogenic mutations in BRCA2. In patients, a variant of uncertain significance was found in BRCA2, RAD50, MRE11A and CDH1. The Manchester scoring system showed a high accuracy (87.5%), high sensitivity (85.7%) and high specificity (88.9%) for the prediction of pathogenic non-founder BRCA1/2 mutations. Conclusion: A relatively high incidence of pathogenic non-founder BRCA1/2 mutations was observed in a founder population. The Manchester scoring system predicted the probability of non-founder pathogenic mutations with high accuracy.publishersversionPeer reviewe

The relationship between wealth and loneliness among older people across Europe: Is social participation protective?

Objective: 1. Examine the relationship between household wealth, social participation and loneliness among older people across Europe. 2. Investigate whether relationships vary by type of social participation (charity/volunteer work, sports/social clubs, educational/training course, and political/community organisations) and gender. 3. Examine whether social participation moderates the association between wealth and loneliness. Methods: Data (N = 29,795) were taken from the fifth wave of the Survey of Health, Ageing and Retirement in Europe (SHARE), which was collected during 2013 from 14 European countries. Loneliness was measured using the short version of the Revised-University of California, Los Angeles (R-UCLA) Loneliness Scale. We used multilevel logistic models stratified by gender to examine the relationships between variables, with individuals nested within countries. Results: The risk of loneliness was highest in the least wealthy groups and lowest in the wealthiest groups. Frequent social participation was associated with a lower risk of loneliness and moderated the association between household wealth and loneliness, particularly among men. Compared to the wealthiest men who often took part in formal social activities, the least wealthy men who did not participate had greater risk of loneliness (OR = 1.91, 95% CI: 1.44 to 2.51). This increased risk was not observed among the least wealthy men who reported frequent participation in formal social activities (OR = 1.12, 95% CI: 0.76 to 1.67). Conclusion: Participation in external social activities may help to reduce loneliness among older adults and potentially acts as a buffer against the adverse effects of socioeconomic disadvantage

A critical review and development of a conceptual model of exclusion from social relations for older people

Social exclusion is complex and dynamic, and it leads to the non-realization of social, economic, political or cultural rights or participation within a society. This critical review takes stock of the literature on exclusion of social relations. Social relations are defined as comprising social resources, social connections and social networks. An evidence review group undertook a critical review which integrates, interprets and synthesizes information across studies to develop a conceptual model of exclusion from social relations. The resulting model is a subjective interpretation of the literature and is intended to be the starting point for further evaluations. The conceptual model identifies individual risks for exclusion from social relations (personal attributes, biological and neurological risk, retirement, socio-economic status, exclusion from material resources and migration). It incorporates the evaluation of social relations, and the influence of psychosocial resources and socioemotional processes, sociocultural, social-structural, environmental and policy contextual influences on exclusion from social relations. It includes distal outcomes of exclusion from social relations, that is, individual well-being, health and functioning, social opportunities and social cohesion. The dynamic relationships between elements of the model are also reported. We conclude that the model provides a subjective interpretation of the data and an excellent starting point for further phases of conceptual development and systematic evaluation(s). Future research needs to consider the use of sophisticated analytical tools and an interdisciplinary approach in order to understand the underlying biological and ecopsychosocial associations that contribute to individual and dynamic differences in the experience of exclusion from social relation