We analysed seven genetic polymorphisms that are candidates to explain individual variations in human endurance phenotypic traits, at least in Caucasian people (ACE Ins/Del, ACTN3 Arg577Ter, AMPD1 Gln12Ter, CKMM 1170 bp/985 + 185 bp, HFE His63Asp, GDF‐8 Lys153Arg and PPARGC1A Gly482Ser) in 46 world‐class endurance athletes and 123 controls (all Spanish Caucasians). Using the model developed by Williams & Folland we determined (1) the ‘total genotype score’ (TGS, from the accumulated combination of the seven polymorphisms, with a maximum value of ‘100’ for the theoretically optimal polygenic score) in the non‐athlete (control) group, in the athlete group and in the total Spanish population, and (2) the probability for the occurrence of Spanish individuals with the ‘perfect’ polygenic endurance profile (i.e. TGS = 100). The probability of a Spanish individual possessing a theoretically optimal polygenic profile for up to the seven candidate genetic polymorphisms we studied was very small, i.e. ∼0.07% (or 1 in 1351 Spanish individuals). The mean TGS was higher in athletes (70.22 ± 15.58) than in controls (62.43 ± 11.45) and also higher than predicted for the total Spanish population (60.80 ± 12.1), suggesting an overall more ‘favourable’ polygenic profile in the athlete group. However, only three of the best Spanish endurance athletes (who are also amongst the best in the world) had the best possible score for up to six genes and none of them had the optimal profile. Other polymorphisms yet undiscovered as well as several factors independent of genetic endowment may explain why some individuals reach the upper end of the endurance performance continuum.

The randomized controlled trial “Physical Activity in Pediatric Cancer” determined the effects of an inhospital exercise intervention combining aerobic and muscle strength training on pediatric cancer patients with solid tumors undergoing neoadjuvant chemotherapy. Participants were allocated to an exercise (n = 24, 17 boys; mean ± SEM age, 10 ± 1 yr) or control group (n = 25, 18 boys; 11 ± 1 yr). Training included three sessions per week for 19 ± 2 wk. Participants were assessed at treatment initiation, termination, and 2 months after end treatment. The primary endpoint was muscle strength (as assessed by upper and lower-body five-repetition-maximum tests). Secondary endpoints included cardiorespiratory fitness, functional capacity during daily life activities, physical activity, body mass and body mass index, and quality of life. Most sessions were performed in the hospital’s gymnasium. Adherence to the program averaged 68% ± 4% and no major adverse events or health issues were noted. A significant interaction (group–time) effect was found for all five-repetition maximum tests (leg/bench press and lateral row; all P < 0.001). Performance significantly increased after training (leg press: 40% [95% confidence interval [CI], 15–41 kg); bench press: 24% [95% CI, 6–14 kg]; lateral row 25% [95% CI, 6–15 kg]), whereas an opposite trend was found in controls. Two-month post values tended to be higher than baseline for leg (P = 0.017) and bench press (P = 0.014). In contrast, no significant interaction effect was found for any of the secondary endpoints. An inhospital exercise program for pediatric cancer patients with solid tumors undergoing neoadjuvant treatment increases muscle strength despite the aggressiveness of such therapy.

Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence) with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A) [rs1801272], CYP2A6*9 (−48T>G) [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T) [rs8192789], CYP2A13*3 (7520C>G), CYP2A13*4 (579G>A), CYP2A13*7 (578C>T) [rs72552266], CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A) [rs1800497], 5HTT LPR, HTR2A −1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126) and ethnically matched never smokers (controls, N = 80). The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A) polymorphisms was 3.60 (95%CI: 1.75, 7.44) and 2.63 (95%CI: 1.41, 4.89) respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65). We found a significant genotype effect (all P≤0.017) for the following smoking-related phenotypes: (i) cigarettes smoked per day and CYP2A13*3; (ii) pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A); (iii) nicotine dependence (assessed with the Fagestrom test) and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms) are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5), serotoninergic (HTR2A), opioid (OPRM1) or cannabinoid receptors (CNR1).