RESUMO
The occurrence of a second primary esophageal carcinoma (EC) in long-term cancer survivors may represent a late effect of previous radio-chemotherapeutic treatment. To identify the genetic factors that could increase this risk, we analyzed nine variants within ERCC1, XPD, XRCC1 and XRCC3 DNA repair pathway genes, and GSTP1, TP53 and MDM2 genes in 61 patients who received radio-chemotherapy for a prior lymphoma or breast cancer; 29 of them had a second primary EC. This cohort consists of 22 esophageal squamous cell carcinoma (ESCC) and 7 esophageal adenocarcinoma (EADC) patients. A validation cohort of 154 patients with sporadic EC was also included. The XPD Asp312Asn (rs1799793) was found to be associated with the risk of developing second primary ESCC (P=0.015). The resultant variant was also involved in the onset of sporadic ESCC (P=0.0018). To know in advance who among long-term cancer survivors have an increased risk of EC could lead to a more appropriate follow-up strategy.
Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/terapia , Carcinoma de Células Escamosas/genética , Quimiorradioterapia , Neoplasias Esofágicas/genética , Variação Genética , Linfoma/terapia , Segunda Neoplasia Primária/genética , Sobreviventes , Proteína Grupo D do Xeroderma Pigmentoso/genética , Adenocarcinoma/diagnóstico , Neoplasias da Mama/patologia , Carcinoma de Células Escamosas/diagnóstico , Estudos de Casos e Controles , Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas do Esôfago , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Linfoma/diagnóstico , Masculino , Segunda Neoplasia Primária/diagnóstico , Fenótipo , Projetos Piloto , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
UNLABELLED: Bone loss was confirmed after 90 days in 50 6-month-old male Sprague Dawley rats that were sham-operated or orchidectomized (ORX). In this study, we have shown that dried plum (DP) has potent effects on bone in terms of bone mass, microarchitecture, and strength in osteopenic male rats. Although these changes may be mediated through the suppression of bone resorption, the fact that the restoration in some of the bone structural and biomechanical parameter shares some similarities with parathyroid hormone (PTH) should not be overlooked. Further investigation is needed on a mechanistic level to clarify the influence of DP on bone metabolism. INTRODUCTION: This study was designed to investigate the extent to which DP reverses bone loss in osteopenic ORX rats and to compare its effects to PTH. MATERIALS AND METHODS: Fifty, 6-month-old male Sprague Dawley rats were sham-operated or ORX, and bone loss was confirmed after 90 days. The ORX groups were assigned to control (AIN-93M) diet, 25% DP diet, or PTH (80 microg/kg) for 90 days. RESULTS: DP induced an 11% increase in vertebral and femoral BMD compared to ORX-controls. BMD in the PTH-treated group was increased by 20.7% (vertebra) and 17.9% (femur). Vertebral trabecular bone volume (BV/TV) and number were increased by DP and trabecular separation was decreased compared to controls, which were similar to PTH. Alterations in trabecular bone of the femur were similar to those in the vertebra, but DP did not restore BV/TV to the same extent. Cortical thickness was improved by DP and further enhanced by PTH. DP tended to decrease urinary deoxypyridinoline and calcium, but did not alter alkaline phosphatase or osteocalcin. CONCLUSION: We conclude that though the degree of improvement was not equivalent to PTH with regard to all parameters, DP reverses bone loss due to ORX and the mechanisms should be further investigated.
