No consensus exists about when researchers need additional participant consent (re-consent) to submit existing data to the federal database of Genotypes and Phenotypes (dbGaP). Reconsent for submission of their data to dbGaP was sought from 1,340 study participants, 1,159 (86%) of whom agreed. We invited the first 400 of those who agreed to complete a telephone survey about their reasoning for their consent decision and their satisfaction with the re-consent process; 365 participants completed the survey. Respondents reported that it was very (69%) or somewhat (21%) important that they were asked for their permission. Many respondents considered alternatives to consent, such as notification-only or opt-out, to be unacceptable (67% and 40%, respectively). These results suggest that re-consent for dbGaP deposition may be advisable in certain cases to anticipate and honor participant preferences.

Background Breast cancer tends to occur in an older age group of women also burdened with comorbidities such as cardiovascular disease (CVD). Numerous medications used to manage CVD (e.g., statins and antihypertensives) are hypothesized to alter breast cancer risk, but there are few studies on breast cancer outcomes. The COMBO (COmmonly used Medications and Breast Cancer Outcomes) cohort was developed to study how medications and co-morbidities influence breast cancer prognosis. Methods Cohort study among adult women, diagnosed with incident early stage breast cancer, and enrolled in an integrated health plan. Data sources included health plan administrative databases, Surveillance, Epidemiology, and End Results tumor registry, and medical records. Statins, angiotensin converting enzyme inhibitors (ACEI), beta blockers (BB), calcium blockers, and diuretics were the exposures of interest. The outcome was second breast cancer events (SBCE) defined as recurrence or second primary breast cancer. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for SBCE and components of SBCE. Results 4,216 women were followed for a median of 6.3 years, and 13.2% experienced a SBCE (first of: n=415 recurrences and n=143 second primary breast cancers). Compared to non-users, we observed an increased risk of second primary breast cancer with ACEI use (HR=1.66; 95% CI, 1.06–2.58) and an increased risk of recurrence with BB use (HR=1.29; 95% CI, 1.01–1.64). There was suggestion of a reduced risk of SBCE with statin use (HR=0.82; 95% CI, 0.62–1.08) and second primary breast cancer with BB use (HR=0.77; 95% CI, 0.50–1.19). No differences in outcomes were observed by duration of medication use. Conclusions The majority of CVD medications evaluated in this study appear safe with respect to SBCE, but ACEI and BB use warrant further evaluation. The study presented is one example of the questions that can be addressed using the COMBO cohort.

Targeted diversification of immunoglobulin variable regions is induced by activation-induced deaminase and may occur by either somatic hypermutation or gene conversion. MRE11-RAD50-NBS1 (MRN) is a ubiquitous and conserved nuclease complex critical for DNA break repair and is essential in class-switch recombination. Here we show that ectopic expression of NBS1, the regulatory subunit of MRN, accelerated hypermutation in the human B cell line Ramos and accelerated gene conversion in the chicken B cell line DT40. In both cases, accelerated diversification depended on MRN complex formation. These data suggest that MRN promotes DNA cleavage and/or mutagenic repair of lesions initiated by activation-induced deaminase, acting in the shared pathway of immunoglobulin gene diversification.