Koboldt et al. Page 1456

To identify common genetic variants linked to aggressive prostate cancer, Koboldt and colleagues used whole-exome sequencing followed by targeted sequencing in aggressive prostate cancer patients and disease-free controls in both African and European Americans. In each population, the authors tested rare variants for association using two gene-based aggregation tests. TET2 in African Americans was associated with aggressive disease, with 24.4% of cases harboring a rare deleterious variant, compared to 9.6% of controls. Eight additional genes were identified with suggestive evidence of association as well as rare truncation variants. These findings suggest that rare variants influence risk of clinically relevant prostate cancer and if validated could serve to identify men for screening, prophylaxis, and treatment.

Román et al. Page 1464

The effects of use of different types of hormone therapy (HT) on breast cancer risk according to prognostic factors are largely unknown. Román and colleagues linked data from the Norwegian Prescription Database and the Cancer Registry of Norway to estimate the rate ratios and 95% confidence intervals for breast cancer in relation to HT. Users of the most common estrogen and progestin combinations were at a 4- to 5-fold elevated risk of grade I tumors, and estradiol–NETA users were also at a 2- to 3-fold increased risk of medium differentiated (grade II) tumors. The HT preparations most commonly used in the Nordic countries are associated with both breast cancers with good and less favorable prognosis characteristics.

Durham et al. Page 1474

Health insurance may lengthen or inhibit time to follow-up after positive screening mammography. Durham and colleagues assessed the association between insurance status and time to initial diagnostic follow-up after a positive screening mammogram. Among 43,026 women included in the study, 73% were <65 years and 27% were 65+. Median time until initial diagnostic follow-up was similar by age group and insurance status. In the adjusted model for women <65, uninsured women experienced a longer time to initiation of diagnostic follow-up versus women with private insurance. There was also an increased odds of these uninsured women not meeting the CDC guideline for follow-up within 60 days. Among women ages 65+, women with private insurance experienced a faster time to follow-up compared to women with Medicare and private insurance.

Loftfield et al. Page 1483

The gut metabolome may be associated with incidence and progression of measuring metabolite levels in the feces. But questions remain with regards to the effects of fecal sample collection methods on metabolomic measures. Loftfield and colleagues collected fecal samples from 18 volunteers using four methods: no solution, 95% ethanol, fecal occult blood test (FOBT) cards, and fecal immunochemical test (FIT). One set of samples was frozen after collection and a second set was frozen after 96 hours at room temperature. Intraclass correlation coefficients (ICC) estimating technical reproducibility were high for replicate samples for each collection method, and ICCs estimating stability at room temperature were high for 95% ethanol and FOBT but not FIT. Future epidemiologic studies should collect feces using 95% ethanol or FOBT if interested in studying fecal metabolomics.