Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study.

Clonal hematopoiesis of indeterminate potential (CHIP) is suspected of being a risk factor for patients with cancer. This study aimed to assess the clinical consequences of CHIP in patients with lymphoma intended for high-dose chemotherapy and autologous stem-cell transplantation (ASCT) in a population-based setting. We identified 892 lymphoma patients who had undergone stem cell harvest at all transplant centers in Denmark. A total of 565 patients had an available harvest sample, which was analysed for CHIP by next-generation sequencing, and the median follow-up was 9.1 years. Of the patients who were intended for immediate ASCT, 25.5% (112/440) carried at least one CHIP mutation. In contrast to previous single-center studies CHIP was not associated with inferior overall survival (OS) in multivariate analyses. However, patients with mutations in genes of the DNA repair pathway (PPM1D, TP53, RAD21, BRCC3) had a significant inferior OS (HR after 1 year of follow-up 2.79, 95% confidence interval 1.71-4.56; p < 0.0001), which also was evident in multivariate analysis (p = 0.00067). These patients had also increased rates of therapy-related leukemia and admission to intensive care. Furthermore, in patients who did not undergo immediate ASCT, a significant inferior OS of individuals with DNA repair mutations was also identified (p = 0.003).

Androgen receptor CAG and GGN repeat polymorphisms influence performance in boys and girls.

BACKGROUND: Shorter CAG and GGN androgen receptor (AR) repeat polymorphisms are associated with stronger androgen signaling, and therefore, could influence lean mass and exercise performance during growth. METHODS: Physical fitness and body composition were measured by standardized procedures and the length of CAG and GGN repeats was determined by PCR and fragment analysis in 152 boys (11.5±2.6 years; Tanner ≤5) and 116 girls (10.1±3.2 years; Tanner ≤5). Individuals were grouped as CAG short (CAGS) if harboring repeat lengths of ≤21 and CAG long (CAGL) if CAG >21. Moreover, subjects were grouped as GGN short (GGNS) if harboring repeat lengths of ≤23 and GGN long (GGNL) if GGN>23. RESULTS: No significant differences in anthropometrics and body composition were observed between either CAGS and CAGL groups and GGNS and GGNL groups. Boys harboring CAGS completed the 300-meter test faster than their CAGL counterparts. Moreover, girls from the GGNL group showed a significant higher VO2max than those in the GGNS group. CONCLUSIONS: In summary, carrying a short allele of the androgen receptor CAG repeat polymorphism is associated to higher anaerobic performance in boys, whereas long alleles of androgen receptor GGN polymorphisms are associated to higher aerobic capacity in girls.

ANDROGEN RECEPTOR CAG AND GGN REPEAT POLYMORPHISMS AND BONE MASS IN BOYS AND GIRLS.

INTRODUCTION: the human androgen receptor (AR) gene possesses two trinucleotide polymorphic repeats, (CAG and GGN) that affect the amount of AR protein translated. In this study, we genotyped these polymorphic tracts in a representative sample of Caucasian children (Tanner ≤ 5), 152 boys (11.5 } 2.6 yrs) and 116 girls (10.1 } 3.2 yrs) from Spain and investigated their association with bone mass. METHODS: the length of CAG and GGN repeats was determined by PCR and fragment analysis. Body composition was assessed by dual energy x-ray absorptiometry (DXA). Individuals were grouped as CAG short (CAGS) if harboring repeat lengths of ≤ 21 and CAG long (CAGL) if CAG > 21. Moreover, subjects were grouped as GGN short (GGNS) if harboring repeat lengths of ≤ 23 and GGN long (GGNL) if GGN > 23. RESULTS: in boys, significant differences in height, body mass, whole body bone mineral density (BMD) and content (BMC), upper extremities BMC, lower extremities BMC, femoral neck BMD, Ward's triangle BMC and BMD and lumbar spine BMD were observed between CAGS and CAGL groups (P < 0.05). Thus, upper extremities BMD differed between GGNS and GGNL groups. After adjusting for confounding variables, only upper extremities BMD between GGNS and GGNL groups remained significant (P < 0.05). No differences were observed in girls in any measured site in relation to either CAG or GGN polymorphisms length. CONCLUSIONS: our results support the hypothesis that longer alleles of the AR CAG and GGN polymorphisms are associated with increased bone mass in prepubertal boys.

Introducción: el gen humano del receptor de androgenos (AR) posee dos repeticiones polimorficas de trinucleotidos (CAG y GGN) que afectan a la cantidad de proteina AR traducida. En este estudio, genotipamos esos tractos polimorficos en una muestra representativa de ninos caucasicos espanoles (Tanner ≤ 5), compuesta por 152 ninos (11.5 } 2.6 anos) y 116 ninas (10.1 } 3.2 anos) e investigamos su asociacion con la masa osea. Métodos: la longitud de las repeticiones CAG y GGN se determino mediante PCR y analisis de fragmentos. La composicion corporal se midio mediante absorciometria dual de rayos X (DXA). Los participantes fueron agrupados como CAG cortos (CAGS) si poseian una longitud de repeticiones ≤ 21 y CAG largos si esta era > 21. Ademas, los participantes se agruparon como GGN cortos (GGNS) si poseian una longitud de repeticiones ≤ 23 y GGN largos (GGNL) si esta era > 23. Resultados: en los ninos se encontraron diferencias en talla, peso corporal, densidad mineral osea (BMD) y contenido mineral oseo (BMC) del cuerpo entero, BMC de las extremidades superiores e inferiores, BMD del cuello del femur, BMC y BMD del triangulo de Ward's y BMD de la espina lumbar entre los grupos CAGS y CAGL (P < 0,05). Ademas, el BMD de las extremidades superiores fue significativamente diferente entre los grupos GGNS y GGNL. Tras ajustar por variables confusoras, la unica diferencia que se mantuvo significativa fue la del BMD en las extremidades superiores entre los grupos GGNS y GGNL (P < 0,05). No se observaron diferencias entre los grupos CAG y GGN y la masa osea en las ninas. Conclusiones: nuestros resultados apoyan la hipotesis de que los alelos largos de los polimorfismos CAG y GGN del AR estan asociados con una mayor masa osea en ninos prepuberes.

Androgen receptor CAG and GGN repeat polymorphisms and bone mass in boys and girls / Polimorfismos CAG y GGN del gen del receptor de andrógenos y masa ósea en niños y niñas

Introduction: the human androgen receptor (AR) gene possesses two trinucleotide polymorphic repeats, (CAG and GGN) that affect the amount of AR protein translated. In this study, we genotyped these polymorphic tracts in a representative sample of Caucasian children (Tanner ≤5), 152 boys (11.5±2.6 yrs) and 116 girls (10.1±3.2 yrs) from Spain and investigated their association with bone mass. Methods: the length of CAG and GGN repeats was determined by PCR and fragment analysis. Body composition was assessed by dual energy x-ray absorptiometry (DXA). Individuals were grouped as CAG short (CAGS) if harboring repeat lengths of ≤21 and CAG long (CAGL) if CAG >21. Moreover, subjects were grouped as GGN short (GGNS) if harboring repeat lengths of ≤23 and GGN long (GGNL) if GGN >23. Results: in boys, significant differences in height, body mass, whole body bone mineral density (BMD) and content (BMC), upper extremities BMC, lower extremities BMC, femoral neck BMD, Ward’s triangle BMC and BMD and lumbar spine BMD were observed between CAGS and CAGL groups (P<0.05). Thus, upper extremities BMD differed between GGNS and GGNL groups. After adjusting for confounding variables, only upper extremities BMD between GGNS and GGNL groups remained significant (P<0.05). No differences were observed in girls in any measured site in relation to either CAG or GGN polymorphisms length. Conclusions: our results support the hypothesis that longer alleles of the AR CAG and GGN polymorphisms are associated with increased bone mass in prepubertal boys (AU)

Introducción: el gen humano del receptor de andrógenos (AR) posee dos repeticiones polimórficas de trinucleótidos (CAG y GGN) que afectan a la cantidad de proteína AR traducida. En este estudio, genotipamos esos tractos polimórficos en una muestra representativa de niños caucásicos españoles (Tanner ≤5), compuesta por 152 niños (11.5±2.6 años) y 116 niñas (10.1±3.2 años) e investigamos su asociación con la masa ósea. Métodos: la longitud de las repeticiones CAG y GGN se determinó mediante PCR y análisis de fragmentos. La composición corporal se midió mediante absorciometría dual de rayos X (DXA). Los participantes fueron agrupados como CAG cortos (CAGS) si poseían una longitud de repeticiones ≤21 y CAG largos si esta era >21. Además, los participantes se agruparon como GGN cortos (GGNS) si poseían una longitud de repeticiones ≤23 y GGN largos (GGNL) si esta era >23. Resultados: en los niños se encontraron diferencias en talla, peso corporal, densidad mineral ósea (BMD) y contenido mineral óseo (BMC) del cuerpo entero, BMC de las extremidades superiores e inferiores, BMD del cuello del fémur, BMC y BMD del triángulo de Ward’s y BMD de la espina lumbar entre los grupos CAGS y CAGL (P<0,05). Además, el BMD de las extremidades superiores fue significativamente diferente entre los grupos GGNS y GGNL. Tras ajustar por variables confusoras, la única diferencia que se mantuvo significativa fue la del BMD en las extremidades superiores entre los grupos GGNS y GGNL (P<0,05). No se observaron diferencias entre los grupos CAG y GGN y la masa ósea en las niñas. Conclusiones: nuestros resultados apoyan la hipótesis de que los alelos largos de los polimorfismos CAG y GGN del AR están asociados con una mayor masa ósea en niños prepúberes (AU)