Publications

INTRODUCTION

Percent mammographic density (PMD) adjusted for age and body mass index is one of the strongest risk factors for breast cancer and is known to be approximately 60% heritable. Here we report a finding of an association between genetic ancestry and adjusted PMD.

METHODS

We selected self-identified Caucasian women in the California Pacific Medical Center Research Institute Cohort whose screening mammograms placed them in the top or bottom quintiles of age-adjusted and body mass index-adjusted PMD. Our final dataset included 474 women with the highest adjusted PMD and 469 with the lowest genotyped on the Illumina 1 M platform. Principal component analysis (PCA) and identity-by-descent analyses allowed us to infer the women's genetic ancestry and correlate it with adjusted PMD.

RESULTS

Women of Ashkenazi Jewish ancestry, as defined by the first principal component of PCA and identity-by-descent analyses, represented approximately 15% of the sample. Ashkenazi Jewish ancestry, defined by the first principal component of PCA, was associated with higher adjusted PMD (P = 0.004). Using multivariate regression to adjust for epidemiologic factors associated with PMD, including age at parity and use of postmenopausal hormone therapy, did not attenuate the association.

CONCLUSIONS

Women of Ashkenazi Jewish ancestry, based on genetic analysis, are more likely to have high age-adjusted and body mass index-adjusted PMD. Ashkenazi Jews may have a unique set of genetic variants or environmental risk factors that increase mammographic density.

Previous studies examining communication of BRCA1/2 results with relatives and family uptake of BRCA1/2 testing have sampled from predominantly white, high SES cohorts ascertained solely from tertiary care centers. No studies have focused on family communication and testing among relatives of diverse BRCA1/2 carriers. We conducted structured interviews with 73 BRCA1/2 carriers identified at a public hospital and a tertiary cancer center. We asked participants if each first- and second-degree relative was aware of their BRCA1/2 results and whether or not each relative had tested. Generalized estimating equations identified rates and predictors of family communication and testing. Participants disclosed their test results to 73 % of 606 eligible relatives and 31 % of 514 eligible relatives tested. Communication and testing rates were similar for relatives of participants from the public hospital and the tertiary cancer center. Hospital site was not a significant predictor of either result disclosure or relative uptake of testing. African American and Asian/Pacific Islander participants were significantly less likely to disclose their results to their relatives; relatives of African American participants were significantly less likely to test. Addressing these disparities will require further research into the best ways to facilitate family communication and counsel at-risk relatives of racially and socioeconomically diverse BRCA1/2 mutation carriers.

AIMS

Galectin-3 is a prognostic heart failure (HF) biomarker that may mediate cardiac fibrosis. We examined the value of serial galectin-3 measurement for prognosis and response to therapy in chronic HF.

METHODS AND RESULTS

A total of 151 subjects with LV systolic dysfunction (LVSD) were followed through 908 visits over 10 ± 3 months. The amount of time spent with a galectin-3 level ≤ 20.0 ng/mL and changes between baseline and subsequent values were considered across visits, and used to assess risk for adverse cardiovascular (CV) events and associations with LV remodelling. Medication effects on galectin-3 were examined. Median galectin-3 values at baseline, 3 months, and 6 months were higher in patients with CV events (21.7 vs. 18.4 ng/mL, P = 0.03; 21.7 vs. 16.5 ng/mL, P = 0.03; 23.2 vs. 16.0 ng/mL, P = 0.007). Galectin-3 concentration changed in 35.2% of subjects during study procedures; time spent at ≤ 20.0 ng/mL was significantly associated with a lower rate of CV events, independently predicted fewer CV events even adjusted for relevant variables including study allocation, NT-proBNP, and renal function [odds ratio (OR) = 0.90; P = 0.05], and predicted increase in LV ejection fraction (OR = 1.20; P = 0.04). Serial galectin-3 measurement at 6 months added prognostic value beyond the baseline level (P = 0.02). There were no significant effects of medications on galectin-3 levels.

CONCLUSION

In chronic HF due to LVSD, serial galectin-3 measurement adds incremental prognostic information and predicts LV remodelling. In this study, HF therapies had no clear effects on galectin-3 levels.