AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

Gas exchange kinetics in elite runners

[Extract] Oxygen uptake (VO₂) kinetics, measured in the frequency domain, have been shown to be faster in elite endurance runners compared to elite sprinters (Edwards et al., 1999). Since carbon dioxide output (VCO₂) kinetics have been shown to be delayed following 6 months sprint and strength training in footballers (Fukuoka et al 1997) it might be expected that VCO₂ kinetics would also differentiate sprinters from endurance runners

Time domain analysis of oxygen uptake kinetics in elite runners by pseudo random binary sequence (PRBS) exercise

Oxygen uptake kinetics assessed in the frequency domain are known to be differentially faster in elite endurance runners than in elite sprinters. Breath-by-breath data from PRBS testing have routinely been analysed by application of Fourier methods, however, it is possible to analyse the data in the time domain in the form of a Total Lag Time (TLT). In this study, correlational techniques were applied to yield an output response to a work rate input. An autocorrelation function was performed on the input work rate (WR) and a cross correlation function was performed on input (WR) and output (vO₂). The cross correlation function was analysed by fitting a linear summation of the ramp form of a two-component exponential function to a triangular pulse. Twelve elite male sprinters and 12 elite male endurance runners completed 3 identical PRBS cycles of 300 s with 20 s work rate changes between 25 and 85 W on an electrically braked cycle ergometer at a pedal cadence of 1 Hz. Oxygen uptake was measured on a breath-by-breath basis using a respiratory mass spectrometer. Statistical analysis using the analysis of variance revealed significantly faster oxygen uptake kinetics (TLT) in the elite endurance runners compared with the elite sprinters (33.3 s 3.39SD and 39.91 s 7.14SD respectively) (p < 0.01). The results of this study show that time domain analysis represents a possible alternative to frequency analysis in the study of oxygen uptake kinetics described by PRBS exercise

The test-retest reliability of gas exchange kinetics in humans using a pseudo random binary sequence exercise test

The purpose of this study was to compare the test-retest reliability of oxygen uptake (VO2) kinetics with carbon dioxide output (VCO2) kinetics using a pseudo random binary sequence (PRBS) exercise test. A reliable test of gas exchange kinetics would have the potential of being applied as a sports fitness test. Ten healthy male subjects agreed to participate in the study and all subjects completed two identical PRBS exercise tests (test 1 and test 2), separated by a 30 min period of inactivity. Three consecutive 300 s PRBS cycles were completed in each test with 20 s exercise intensity changes between 25 and 85 W using an electrically braked cycle ergometer. Fourier analysis was computed for frequencies 3.3, 6.7 and 10 mHz. Statistical analysis by two-way ANOVA with repeated measures did not reveal significant differences between test 1 and test 2 for either VO2 kinetics or VCO2 kinetics. Static gain of VO2 for test 1 [9.11 (SD 0.59) ml.min-1.W-1] and test 2 [9.23 (SD 0.64) ml.min-1.W-1] did not differ significantly between tests. The 95% limits of agreement for VCO2 kinetics displayed increased variability in comparison to VO2 kinetics at each frequency of amplitude ratio and phase shift. Systematic bias ranged between 0% and 4%, except at frequency 10 mHz of VCO2 kinetics phase shift which showed a 10% bias for slower VO2 kinetics in test 2. It is possible that the increased variability of VCO2 kinetics compared to VO2 kinetics might be attributable to a lower signal to noise ratio in VCO2 kinetics, variations in ventilation or the storage mechanisms of CO2. The lower variability of VO2 kinetics compared with VCO2 kinetics suggests that the PRBS test of VO2 kinetics has the greater potential for further development as an indicator of aerobic fitness