A genome-wide association scan on estrogen receptor-negative breast cancer

Introduction

Breast cancer is a heterogeneous disease and may be characterized on the basis of whether estrogen receptors (ER) are expressed in the tumour cells. ER status of breast cancer is important clinically, and is used both as a prognostic indicator and treatment predictor. In this study, we focused on identifying genetic markers associated with ER-negative breast cancer risk.

Methods

We conducted a genome-wide association analysis of 285,984 single nucleotide polymorphisms (SNPs) genotyped in 617 ER-negative breast cancer cases and 4,583 controls. We also conducted a genome-wide pathway analysis on the discovery dataset using permutation-based tests on pre-defined pathways. The extent of shared polygenic variation between ER-negative and ER-positive breast cancers was assessed by relating risk scores, derived using ER-positive breast cancer samples, to disease state in independent, ER-negative breast cancer cases.

Results

Association with ER-negative breast cancer was not validated for any of the five most strongly associated SNPs followed up in independent studies (1,011 ER-negative breast cancer cases, 7,604 controls). However, an excess of small P-values for SNPs with known regulatory functions in cancer-related pathways was found (global P = 0.052). We found no evidence to suggest that ER-negative breast cancer shares a polygenic basis to disease with ER-positive breast cancer.

Conclusions

ER-negative breast cancer is a distinct breast cancer subtype that merits independent analyses. Given the clinical importance of this phenotype and the likelihood that genetic effect sizes are small, greater sample sizes and further studies are required to understand the etiology of ER-negative breast cancers.     

Physical activity,heart rate variability–based stress and recovery,and subjective stress during a 9‐month study period

The aim of this study was to investigate the association between physical activity (PA) and objective heart rate variability (HRV)‐based stress and recovery with subjective stress in a longitudinal setting. Working‐age participants (n = 221; 185 women, 36 men) were overweight (body mass index, 25.3–40.1 kg/m²) and psychologically distressed (≥3/12 points on the General Health Questionnaire). Objective stress and recovery were based on HRV recordings over 1–3 work days. Subjective stress was assessed with the Perceived Stress Scale and PA level with a questionnaire. Data were collected at three time points: baseline, 10 weeks post intervention, and at the 36‐week follow‐up. We adopted a latent growth model to investigate the initial level and change in PA, objective stress and recovery, and subjective stress at the three measurement time points. The results showed that initial levels of PA (P < 0.001) and objective stress (P = 0.001) and recovery (P < 0.01) were associated with the change in subjective stress. The results persisted after adjustment for intervention group. The present results suggest that high PA and objectively assessed low stress and good recovery have positive effects on changes in subjective stress in the long‐term.     

Effect of low-dose endurance training on heart rate variability at rest and during an incremental maximal exercise test

We evaluated the effects of low-dose endurance training on autonomic HR control. We assessed the heart rate variability (HRV) of 11 untrained male subjects (36.8 +/- 7.2 years) at rest and during an incremental maximal aerobic exercise test prior to a 7-week preparatory period and prior to and following a 14-week endurance training period, including a low to high intensity exercise session twice a week. Total (0.04-1.2 Hz), low (0.04-0.15 Hz) and high (0.15-1.2 Hz) frequency power of HRV were computed by short-time Fourier transform. The preparatory period induced no change in aerobic power or HRV. The endurance training period increased peak aerobic power by 12% (P < 0.001), decreased the HR (P < 0.01) and increased all HRV indices (P < 0.05-0.01) at absolute submaximal exercise intensities, but not at rest. In conclusion, low-dose endurance training enhanced vagal control during exercise, but did not alter resting vagal HR control.     

Cardiac autonomic responses to standing up and cognitive task in overtrained athletes

This study compared the autonomic responses to an active orthostatic test and Stroop Color Word Test (Stroop) as well as cognitive performance in Stroop in twelve severely overtrained (OA, 6 men and 6 women) and twelve control athletes (CA, 6 men and 6 women). RR-intervals were recorded during the orthostatic test, the Stroop, and a relaxation period succeeding the Stroop. Low frequency power during standing in the orthostatic test was lower in OA than in CA (1322 +/- 955 ms2 vs. 2262 +/- 1029 ms2, p = 0.030, respectively). During Stroop, OA had higher relative total power (50 +/- 47 % vs. 19 +/- 14 % of the individual total power during supine rest after awakening, p = 0.028, respectively) and high frequency power (38.5 +/- 9.4 % vs. 13.5 +/- 2.3 % of the individual high frequency power during supine rest after awakening, p = 0.035, respectively) than CA. In the Stroop, OA made more mistakes than CA (9.7 +/- 6.5 % vs. 5.4 +/- 3.0 %, p = 0.045). The increase in absolute total power from the Stroop to relaxation correlated negatively with the amount of mistakes in the Stroop (r = - 0.588, p = 0.003). Thus, cardiac autonomic modulation during orthostatic task and responses to cognitive task and to relaxation, as well as the cognitive performance were attenuated in severe overtraining.     

The influence of flexed-knee gait on the energy cost of walking in children

There is ah understanding that walking with flexed knees contributes to the increased energy cost of walking found in children with neurological conditions. To determine the influence of flexed-knee gait on energy cost of walking in a group of children without neurological abnormality, the gait patterns of 10 normal children were studied using a Vicon system and standard marker set. A telemetric system (Cosmed K2) was then used to measure the oxygen cost of walking of the same children. The tests were repeated restricting the subjects' knee extension bilaterally, using hinged braces, set to 0, 15, 30, and 45° of flexion. Although the braces themselves caused a significant increase in O₂ cost (mL/kg/m) (P<0.05), due to a decrease in walking speed, no further significant increase in oxygen cost was demonstrated regardless of the degree of knee flexion imposed, despite a significant increase in measured hip flexion and ankle dorsiflexion at the 45° of knee flexion setting (P<0.05). We propose that moderate flexed-knee gait does not of itself cause an increase in the energy cost of walking and that other factors present in the physically disabled child are likely to be implicated.     

CO2 measurements during transcranial Doppler examinations in headache patients: methodological considerations

Transcranial Doppler (TCD) examinations are increasingly being used in studies of headache pathophysiology. Because blood velocity is highly dependent on pCO₂, these parameters should be measured simultaneously. The most common way of performing measurements during TCD examinations is as end-tidal pCO₂ witch a capnograph. When patients are nauseated and vomit, as in migraine, the mask or mouthpiece connected to the capnograph represents a problem. We therefore evaluated whether a transcutaneous pCO₂ electrode was as useful as the capnograph for pCO₂ measurements in TCD examinations. We conclude that this is not the case, and recommend capnographic end-tidal pCO₂ measurements during TCD examinations. However, transcutaneous pCO₂ measurements may represent a supplement to spot measurements of end-tidal pCO₂ in stable conditions when long-term monitoring is needed, and the mask or mouthpiece of the capnograph has to be taken on and off between recordings.