Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
J Cancer Res Clin Oncol. 2012 Nov;138(11):1919-30. doi: 10.1007/s00432-012-1265-4. Epub 2012 Jul 1.
Patients treated for childhood acute lymphoblastic leukemia (ALL) are considered to be at increased risk of developing second neoplasm. The aim of our study was to identify DNA repair polymorphisms contributing to the risk of second neoplasm in clinically well-characterized Slovenian patients treated for childhood ALL.
Pediatric patients diagnosed with ALL between 1971 and 2001 were included in the study. According to the identified clinical risk factors for second neoplasm, a matched set of cases with second neoplasm and controls was selected and genotyped for 11 DNA repair polymorphisms.
Among 359 pediatric patients with ALL, 20 second neoplasms were observed. The dose of radiotherapy (P = 0.011), administration of epipodophyllotoxins (P = 0.006), and the dose of anthracyclines (P < 0.001) showed a significant association with the risk of second neoplasm. Among genetic factors, we observed a significant association of NBN 1197G allele with increased risk of second neoplasms (RR = 4.36; 95 % CI: 1.19-15.98; P = 0.026), while the risk was decreased in carriers of XRCC3-316G allele compared with patients with wild-type genotype (RR = 0.20; 95 % CI: 0.04-0.99; P = 0.049).
Our results suggest an important role of NBN 1197A>G and XRCC3-316A>G polymorphisms in the development of second neoplasm in patients treated for childhood ALL.
接受儿童急性淋巴细胞白血病（ALL）治疗的患者被认为有较高的罹患第二肿瘤的风险。本研究的目的是鉴定与斯洛文尼亚儿童 ALL 治疗患者第二肿瘤风险相关的 DNA 修复多态性。
本研究纳入了 1971 年至 2001 年间被诊断为 ALL 的儿科患者。根据第二肿瘤的明确临床危险因素，选择具有第二肿瘤的匹配病例组和对照组，并对 11 种 DNA 修复多态性进行基因分型。
在 359 例 ALL 儿科患者中，观察到 20 例第二肿瘤。放疗剂量（P = 0.011）、表鬼臼毒素（VP16）的应用（P = 0.006）和蒽环类药物剂量（P < 0.001）与第二肿瘤的风险显著相关。在遗传因素中，我们观察到 NBN 1197G 等位基因与第二肿瘤风险增加显著相关（RR = 4.36；95 % CI：1.19-15.98；P = 0.026），而 XRCC3-316G 等位基因携带者的风险较野生型基因型患者降低（RR = 0.20；95 % CI：0.04-0.99；P = 0.049）。
我们的结果表明，NBN 1197A>G 和 XRCC3-316A>G 多态性在儿童 ALL 治疗患者第二肿瘤的发生中起重要作用。
