Among women with breast cancer and a family history of the disease, the percentage with BRCA1 coding-region mutations is less than the 45 percent predicted by genetic-linkage analysis. These results suggest that even in a referral clinic specializing in screening women from high-risk families, the majority of tests for BRCA1 mutations will be negative and therefore uninformative.

Central core disease (CCD) of muscle is an inherited myopathy which is closely associated with malignant hyperthermia (MH) in humans. CCD has recently been shown to be tightly linked to the ryanodine receptor gene (RYR1) and mutations in this gene are known to be present in MH. Mutation screening of RYR1 has led to the identification of two previously undescribed mutations in different CCD pedigrees. One of these mutations was also detected in an unrelated MH pedigree whose members are asymptomatic of CCD. The data suggest a model to explain how a single mutation may result in two apparently distinct clinical phenotypes.

Early-life exposures may influence the development of breast cancer. The authors examined the association of childhood and adolescent anthropometric factors, physical activity levels, and diet with adult mammographic breast density, a strong risk factor for breast cancer. Women in the Minnesota Breast Cancer Family Study cohort who had undergone mammograms but had not had breast cancer (n=1,893) formed the sample. Information on adolescent exposures, including relative height, weight, and physical activity at ages 7, 12, and 18 years and diet at age 12-13 years, was self-reported during two follow-up studies (1990-2003). Mammographic percent density was estimated using a computer-assisted thresholding program. Statistical analyses were performed using linear mixed-effects models with two-sided tests. Positive associations with height at ages 7 (p<0.001), 12 (p<0.001), and 18 (p<0.001) years and percent density were evident overall and within menopausal status categories. The minimum difference in percent density between the tallest and shortest girls was 3 percent, with a maximum of 7 percent. Weight at age 12 years (p=0.005) and adiposity at age 12 years (p=0.005) were both inversely associated with adult percent density. Adolescent physical activity and diet were unrelated to percent density. These results suggest that adolescent height, a known risk factor for breast cancer, is also associated with mammographic percent density.