RESUMO
Uveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. A genome-wide association study of 259 uveal melanoma patients compared to 401 controls all of European ancestry revealed a candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43-2.05). This locus was replicated in an independent set of 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression of CLPTM1L. In conclusion, the CLPTM1L region contains risk alleles for uveal melanoma susceptibility, suggesting that CLPTM1L could play a role in uveal melanoma oncogenesis.
RESUMO
BACKGROUND: Aging-related muscle loss is a public health problem. We investigated the association of lifestyle and hormonal factors with a prospectively assessed muscle loss in older men. METHODS: Among 608 home-dwelling men, aged 60-85 (mean 68) years, lifestyle and health status were evaluated through a questionnaire. Appendicular skeletal muscle mass was estimated using dual-energy x-ray absorptiometry and calculated as the sum of lean mass of the 4 limbs. Free testosterone concentration was calculated using concentrations of total testosterone and sex hormone-binding globulin. Longitudinal data were analyzed by hierarchical models. RESULTS: Average muscle loss was 0.63 ± 0.05%/year. The results of our multivariable adjusted analyses showed that muscle loss was higher in men whose leisure physical activity was <15 hours/week versus ≥15 hours/week (-0.76 vs -0.57%/year). Age-related acceleration of muscle loss was greater in men with lower total testosterone levels (<10 vs ≥10 nmol/L: -0.10 vs -0.07%/year/year of age at baseline [age]). Men with lower free testosterone (<75 vs ≥75 pmol/L) had greater age-related acceleration of muscle loss (-0.12 vs -0.08%/year/age). Higher parathyroid hormone concentrations were associated with greater age-related acceleration of muscle loss (≥45 vs <45 pg/mL -0.14 vs -0.12%/year/age). Men with type 2 diabetes had higher age-related acceleration of muscle loss versus men without diabetes (-0.08 vs -0.03%/year/age) (All P values are <.05). CONCLUSION: In elderly men, low leisure physical activity, type 2 diabetes, low total and free testosterone, and elevated parathyroid hormone concentrations are associated with greater age-related acceleration of muscle loss. These factors are likely to represent real determinants of aging-related muscle loss in men.