GENETIC PREDISPOSITION TO SECOND MALIGNANT NEOPLASMS FOLLOWING CHILDHOOD

迄今为止的进展：这项研究现已从费城儿童医院（CHOP）招募了124名受试者，其中54名接受了样本。目前正在努力为每例病例找到3个对照，并找到失访病例。 同意书已经签署。 从这些患者中获得了完整的家族史。 目前正在收集血液和肿瘤样本进行基因型检测。 此外，对于GST分析，可以从口腔涂片中获得DNA，目前除血液标本外，还正在收集这些DNA。 我们将继续从肿瘤登记处收到关于符合资格要求的新病例的更新信息。初步结果：1970年至1996年，4796名儿童接受治疗的原发性恶性肿瘤在CHOP。 其中，104人发展为第二恶性肿瘤（SMN），发病密度为每10万人年380例。估计累积发生率为2.3%。 正在进行进一步的数据分析，以计算最常见的第二种恶性肿瘤的SIR。在某些特定的原发性和继发性恶性肿瘤之间发现了关联。 原发性白血病与甲状腺癌（OR=4.9）或CNS肿瘤（OR=1.8）相关。 视网膜母细胞瘤和尤文氏肉瘤患者更容易发展成骨肉瘤（OR分别为10.3和5.1）。表鬼臼毒素暴露与白血病相关（OR=3.2）。放疗与继发性肉瘤的风险轻微相关（OR=1.3），与化疗有协同作用（OR=2.1）。 CNS、甲状腺和乳腺癌（n=21）仅见于接受放射治疗的患者。采用病例对照方法，迄今为止，已对35例病例和1-3例对照进行了家族史的作用评价。 在有和没有SMN的受试者之间，未观察到性别或种族方面的显著差异。 先天性异常或遗传性综合征家族史与SMN风险增加无统计学意义（OR分别为2.5和4.0），一级或二级亲属的癌症家族史也是如此（OR分别为1.5和5.0）。 在这些病例中出现了几个有趣的家族谱系。 将进一步探讨这些问题。

Progress to date: This study has now enrolled 124 subjects from the Children's Hospital of Philadelphia (CHOP), with samples recieved on 54. Ongoing attempts are underway to locate 3 controls for each case, and to locate cases lost to follow-up. Consent forms have been signed. Complete family histories have been obtained from these patients. Collection of blood and tumor samples for genotype testing is currently underway. In addition, for the GST analyses, DNA can be obtained from buccal smears and these are currently being collected in addition to blood specimens. We are continuing to receive updated information from the tumor registry regarding new cases that meet eligibility requirements. Preliminary Results: Between 1970 and 1996, 4796 children were treated for a primary malignancy at CHOP. Of these, 104 developed second malignant neoplasm (SMN), with an incidence density of 380 per 100,000 person-years. The estimated cumulative incidence is 2.3%. Further data analysis is underway to calculate SIR's for the most common second malignancies. Associations were found between certain specific primary and secondary malignancies. Primary Leukemia was associated with thyroid cancer (OR=4.9) or CNS tumor (OR=1.8). Patients with retinoblastoma or Ewing's sarcoma were more likely to develop osteosarcoma (OR=10.3 and 5.1 respectively). Epipodophyllotoxin exposure was associated with leukemia (OR=3.2). Radiation was associated marginally with a risk of secondary sarcoma (OR=1.3), and was synergistic with chemotherapy ((OR=2.1). CNS, thyroid and breast cancer (n=21) were seen only in patients who received radiation. Using case-control methodology, the role of family histories has been evaluted to date on 35 cases and 1-3 controls per case. There were no significant differences noted in gender or race between those with and without an SMN. Family history of congenital anomalies or hereditary syndromes was associated with a statistically non-significant increased risk of SMN (OR=2.5 and 4.0 respectively), as was family history of cancer in either first degree or second degree relatives (OR's 1.5 and 5.0 respectively). Several interesting family pedigrees have emerged among the cases. These will be explored further.