BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition

BARD1 (BRCA1-associated RING-domain 1) is a tumor suppressor whose protein product interacts with BRCA1, and in which rare somatic and germline mutations have been reported in breast, uterine, and endometrial cancers. We aimed to evaluate whether there are BARD1 genetic variants that contribute to breast cancer risk by screening the gene for germline alterations in 45 Finnish familial breast cancer patients and in seven patients with both breast and ovarian cancer. Two of the missense alterations identified (Cys557Ser and Val507Met) were recently suggested to associate with an increased breast cancer risk. We also analyzed these variants in large and independent series of familial and unselected breast cancer patients and healthy controls. No clearly deleterious mutations were detected in the initial mutation screening. No association of the Cys557Ser and breast cancer risk was observed as the variant was found altogether in 1.4% (16/1181) of familial and 2.2% (34/1565) of unselected breast cancer patients, and in 2.5% (27/1083) of healthy controls. The frequency of the Val-allele of the Val507Met variant was modestly higher among breast cancer patients than among healthy controls, although the difference did not reach statistical significance. No statistically significant association of the Cys557Ser or Val507Met variants with any clinicopathologic parameters was observed. These results suggest that the contribution of the BARD1 germline variants to breast cancer predisposition is very limited, and that neither Cys557Ser nor Val507Met have an effect on familial breast cancer susceptibility.     

The complex interplay of cardiovascular system and cognition: how to predict dementia in the elderly?

Prevalence of dementing illnesses is expected to grow due to aging of the population throughout the world. Vascular dementia and Alzheimer's disease share several risk factors and are nowadays considered two ends of a continuum rather than two distinct entities. Traditional cardiovascular risk markers such as diabetes, dyslipidemia, hypertension, metabolic syndrome and adiposity in mid-life are harbingers of cognitive decline, Alzheimer's disease and vascular dementia later in life. In aged populations, only diabetes has been more constantly associated with the development of cognitive dysfunction, while other risk markers have shown more mixed results. Normal aging, co-morbidities and other changes connected to cognitive decline make the interpretation of the risk markers in the elderly challenging and probably explain these contradictory findings. Control of cardiovascular risk factors has been linked to beneficial effects in terms of cognition in cross-sectional and prospective follow up studies, but the results of interventional trials have been disappointing. More research in this area is needed, specifically, placebo-controlled randomized trials in both mid-life and late-life with cognitive dysfunction as a primary endpoint.