A large study of androgen receptor germline variants and their relation to sex hormone levels and prostate cancer risk. Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Background: Androgens are key regulators of prostate gland maintenance and prostate cancer growth, and androgen deprivation therapy has been the mainstay of treatment for advanced prostate cancer for many years. A long-standing hypothesis has been that inherited variation in the androgen receptor (AR) gene plays a role in prostate cancer initiation. However, studies to date have been inconclusive and often suffered from small sample sizes. Objective and Methods: We investigated the association of AR sequence variants with circulating sex hormone levels and prostate cancer risk in 6058 prostate cancer cases and 6725 controls of Caucasian origin within the Breast and Prostate Cancer Cohort Consortium. We genotyped a highly polymorphic CAG microsatellite in exon 1 and six haplotype tagging single nucleotide polymorphisms and tested each genetic variant for association with prostate cancer risk and with sex steroid levels. Results: We observed no association between AR genetic variants and prostate cancer risk. However, there was a strong association between longer CAG repeats and higher levels of testosterone (P = 4.73 × 10−5) and estradiol (P = 0.0002), although the amount of variance explained was small (0.4 and 0.7%, respectively). Conclusions: This study is the largest to date investigating AR sequence variants, sex steroid levels, and prostate cancer risk. Although we observed no association between AR sequence variants and prostate cancer risk, our results support earlier findings of a relation between the number of CAG repeats and circulating levels of testosterone and estradiol.

Towards the integration of Metalib, SFX and PAPI: How to change your metasearcher transparently to the user

To guarantee the success of a virtual library is essential that all users can access all the library resources independently of the user's location.

Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis.

INTRODUCTION Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification. METHODS We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003-02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype. RESULTS Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype. CONCLUSIONS Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes.

Initial complications and factors related to prehospital mortality in acute myocardial infarction with ST segment elevation.

OBJECTIVE Hospital mortality in myocardial infarction ST-elevation myocardial infarction has decreased in recent years, in contrast to prehospital mortality. Our objective was to determine initial complications and factors related to prehospital mortality in patients with acute myocardial infarction with ST segment elevation (STEMI). METHODS Observational study based on a prospective continuous register of patients of any age attended by out-of-hospital emergency teams in Andalusia between January 2006 and June 2009. This includes patients with acute coronary syndrome-like symptoms whose initial ECG showed ST elevation or presumably new left bundle branch block (LBBB). Epidemiological, prehospital data and final diagnostic were recorded. The study included all patients with STEMI on the register, without age restrictions. Forward stepwise logistic regression analysis was performed to control for confounders. RESULTS A total of 2528 patients were included, 24% were women. Mean age 63.4±13.4 years; 16.7% presented atypical clinical symptoms. Initial complications: ventricular fibrillation (VF) 8.4%, severe bradycardia 5.8%, third-degree atrial-ventricular (AV) block 2.4% and hypotension 13.5%. Fifty-two (2.1%) patients died before reaching hospital. Factors associated with prehospital mortality were female sex (OR 2.36, CI 1.28 to 4.33), atypical clinical picture (OR 2.31, CI 1.21 to 4.41), hypotension (OR 4.95, CI 2.60 to 9.20), LBBB (OR 4.29, CI 1.71 to 10.74), extensive infarction (ST elevation in ≥5 leads) (OR 2.53, CI 1.28 to 5.01) and VF (OR 2.82, CI 1.38 to 5.78). CONCLUSIONS A significant proportion of patients with STEMI present early complications in the prehospital setting, and some die before reaching hospital. Prehospital mortality was associated with female sex and atypical presentation, as pre-existing conditions, and hypotension, extensive infarction, LBBB and VF on emergency team attendance.