Cardiorespiratory fitness (CRF) is considered an important indicator of health in children and adults. The main contribution of this paper is an analysis of cardiorespiratory fitness predictive ...models among a population of healthy and young women, using the non-exercise variables. The study was conducted on a group of 154 healthy women (aged 20.3 ± 1.2) from selected academic centers in Poland. The VO2max was measured using a Cosmed K4b2 portable analyzer during a 20 m shuttle test. In addition, selected anthropomotor parameters including body composition components were measured for each subject. The participants’ leisure-time physical activity was assessed using the Minnesota Leisure-Time Physical Activity Questionnaire. The Ridge regression was the most accurate model for estimating VO2max from anthropometric parameters. The most accurate model based on the level of leisure-time physical activity was calculated using stepwise regression for which the prediction error was at the level of 6.68 (mL·kg−1·min−1). The best model calculated from all non-exercise variables (age, anthropometric parameters, and leisure-time physical activity) had only two predictors: waist circumference and total physical activity, and had a prediction error equal to 6.20 (mL·kg−1·min−1).
RAD51 is an important component of double-stranded DNA–repair mechanisms that interacts with both BRCA1 and BRCA2. A single-nucleotide polymorphism (SNP) in the 5′ untranslated region (UTR) of
RAD51, ...135G→C, has been suggested as a possible modifier of breast cancer risk in
BRCA1 and
BRCA2 mutation carriers. We pooled genotype data for 8,512 female mutation carriers from 19 studies for the
RAD51 135G→C SNP. We found evidence of an increased breast cancer risk in CC homozygotes (hazard ratio HR 1.92 95% confidence interval {CI} 1.25–2.94) but not in heterozygotes (HR 0.95 95% CI 0.83–1.07;
P=.002, by heterogeneity test with 2 degrees of freedom df). When
BRCA1 and
BRCA2 mutation carriers were analyzed separately, the increased risk was statistically significant only among
BRCA2 mutation carriers, in whom we observed HRs of 1.17 (95% CI 0.91–1.51) among heterozygotes and 3.18 (95% CI 1.39–7.27) among rare homozygotes (
P=.0007, by heterogeneity test with 2 df). In addition, we determined that the 135G→C variant affects
RAD51 splicing within the 5′ UTR. Thus, 135G→C may modify the risk of breast cancer in
BRCA2 mutation carriers by altering the expression of
RAD51. RAD51 is the first gene to be reliably identified as a modifier of risk among
BRCA1/2 mutation carriers.
Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve ...personalized cancer prevention strategies.
A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated.
The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk.
Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers.
Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk.
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