BRCA1 and BRCA2 mutations in a population-based study of male breast cancer

Background: The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC) in the United Kingdom is not known, and the importance of these genes in the increased risk of female breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear. Methods: We have carried out a population-based study of 94 MBC cases collected in the UK. We screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these cases to calculate the risk of breast cancer to female relatives of MBC cases. We also estimated the contribution of BRCA1 and BRCA2 to this risk. Results: Nineteen cases (20%) reported a first-degree relative with breast cancer, of whom seven also had an affected second-degree relative. The breast cancer risk in female first-degree relatives was 2.4 times (95% confidence interval [CI] = 1.4–4.0) the risk in the general population. No BRCA1 mutation carriers were identified and five cases were found to carry a mutation in BRCA2. Allowing for a mutation detection sensitivity frequency of 70%, the carrier frequency for BRCA2 mutations was 8% (95% CI = 3–19). All the mutation carriers had a family history of breast, ovarian, prostate or pancreatic cancer. However, BRCA2 accounted for only 15% of the excess familial risk of breast cancer in female first-degree relatives. Conclusion: These data suggest that other genes that confer an increased risk for both female and male breast cancer have yet to be found

Animal models of nonalcoholic fatty liver disease

In 1980, Ludwig and colleagues described a series of patients with liver histology characterized by the accumulation of fat and the presence of hepatic necroinflammation in the absence of a history of excessive alcohol consumption. They coined the term nonalcoholic steatohepatitis (NASH), which today is regarded as one of the most common causes of liver disease in affluent countries. NASH is a subset of a larger spectrum of diseases termed fatty liver disease (including alcoholic and nonalcoholic fatty liver disease; AFLD and NAFLD, respectively). NAFLD and NASH are linked to visceral adiposity, insulin resistance, dyslipidemia and type 2 diabetes, and are increasing due to the prevalence of the metabolic syndrome. In this context, research has been undertaken using animals to model human steatosis and NAFLD to NASH disease progression. This Review discusses the prevalent dietary and inflammation-based genetic animal models described in recent years