Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis.

BACKGROUND: The germline BRCA2 mutation is associated with increased prostate cancer (PrCa) risk. We have assessed survival in young PrCa cases with a germline mutation in BRCA2 and investigated loss of heterozygosity at BRCA2 in their tumours. METHODS: Two cohorts were compared: one was a group with young-onset PrCa, tested for germline BRCA2 mutations (6 of 263 cases had a germline BRAC2 mutation), and the second was a validation set consisting of a clinical set from Manchester of known BRCA2 mutuation carriers (15 cases) with PrCa. Survival data were compared with a control series of patients in a single clinic as determined by Kaplan-Meier estimates. Loss of heterozygosity was tested for in the DNA of tumour tissue of the young-onset group by typing four microsatellite markers that flanked the BRCA2 gene, followed by sequencing. RESULTS: Median survival of all PrCa cases with a germline BRCA2 mutation was shorter at 4.8 years than was survival in controls at 8.5 years (P=0.002). Loss of heterozygosity was found in the majority of tumours of BRCA2 mutation carriers. Multivariate analysis confirmed that the poorer survival of PrCa in BRCA2 mutation carriers is associated with the germline BRCA2 mutation per se. CONCLUSION: BRCA2 germline mutation is an independent prognostic factor for survival in PrCa. Such patients should not be managed with active surveillance as they have more aggressive disease.

Effect of low-fat, high-carbohydrate, high-fiber diet on fecal bile acids and neutral sterols.

The effect of a diet low in total fat and high in complex carbohydrates on the excretion of bile acids and neutral sterols and on serum lipids was studied in women, 46-47 years old, who were consuming a mixed Western diet. Participants kept an initial 3-day food record while consuming their normal diet (pre-diet period). During the dietary intervention period (experimental diet) which lasted for 26 days, all volunteers consumed a low-calorie, low-fat (less than 10% of total calories), high-fiber (37 g/day, high-carbohydrate diet. At the 1-year follow-up, the participants completed another 3-day food record, which indicates that these volunteers maintained their caloric and fat intake at levels slightly higher than the experimental diet, but lower than the pre-diet period. Individual 24-hr fecal samples for 2 days and blood samples were collected from the volunteers during each dietary period. Fecal samples were analyzed for neutral sterols and bile acids, and blood samples were analyzed to ascertain cholesterol and triglyceride levels. There were no significant differences in the excretion of neutral sterols between the dietary periods. Fecal secondary bile acids were significantly lower during the experimental and follow-up diet periods compared with the pre-test diet period. Serum cholesterol levels were significantly lower during the experimental and follow-up diet periods than during the pre-test diet period. These results suggest that switching from a high-fat, low-fiber diet to a low-fat, high-fiber diet can reduce the excretion of bile acids which are thought to be involved in the promotion of colon cancer.

Long-term use of a high-complex-carbohydrate, high-fiber, low-fat diet and exercise in the treatment of NIDDM patients.

The purpose of this study was to assess the long-term effects of a high-complex-carbohydrate, high-fiber, low-fat diet and exercise on 69 NIDDM patients. During the initial 26-day program, fasting glucose was reduced from 179.5 +/- 10.6 to 133.5 +/- 4.0 mg/dl. This decrease in fasting glucose was achieved along with the discontinuation of oral hypoglycemic agents in 24 of 31 patients and of insulin in 13 of 18 patients; one patient was placed on insulin. Serum cholesterol and triglycerides were reduced by 25% and 27%, respectively. At 2-3 yr of follow-up, fasting glucose was not significantly different from the value observed at the end of the 26-day program. Compared with the end of the 26-day program, seven more patients were taking oral agents and four more were on insulin. Exercise and diet inventories obtained at follow-up indicated good compliance to the program and also indicated that the main difference between those patients who went back on medication at follow-up compared with those remaining off medication was the percent of calories derived from fat.