Epidemiological and molecular biological study of familial factors in occurrence of children's leukemia

儿童白血病发生家族因素的流行病学及分子生物学研究

• 批准号: 09670380
• 负责人: BESSHO Fumio
• 金额: $ 1.92万
• 依托单位: Kyorin University (2000)The University of Tokyo (1997-1999)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670380/
• 关键词: Pediatric cancer; Familial occurrence; Tumor suppressor genes; Etiological factors; Familial leukemia; Familial cancer; 癌抑制遺伝子; 小児白血病; 家族要因; 疫学; 分子生物学; 腫瘍抑制遺子; MLL遺伝子; p16遺伝子; RAS遺伝子

Objectives : Several evidences showed that some of children's leukemia have their origin in utero and they develop into overt leukemia after one or more additional genetic events. If frequency of mutation is proportional to frequency of DNA replication, active cell division of spermatogonia to produce sperm can accumulate such mutation much more in older male than young male and as the result father of children with leukemia might be older than father of children without cancers. Methods : Data of ages of parents at the time of birth of children with acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), neuroblastoma or hepatoblastoma were provided by the Children's Cancer Registry of Japan. Data of parents of children who visited 5 hospitals for acute illness were served as control. Results : Distribution curves of ages of parents of children with ALL diagnosed at the ages between 2 to 6 years were completely overlapped. Mean ages with SD of father and mother of children with ALL were 383.5 +/- 67.1 months and 348.9 +/- 53.3, respectively. Those of controls were 382.6 +/- 65.3 and 349.4 +/- 54.6, respectively. The results for the children with ALL of other age ranges, AML and embryonal tumors (neuroblastoma, Wilms tumor, hepatoblastoma) were similar. Conclusion : There were no significant differences between ages of either fathers or mothers of children with cancers examined. Hypothesis that older parents might have accumulated carcinogenic mutations in their sperm or ovum was not substantiated.

目的：许多证据表明，一些儿童白血病起源于子宫内，经过一次或多次额外的遗传事件后发展为显性白血病。如果突变的频率与DNA复制的频率成正比，那么精原细胞产生精子的活跃细胞分裂可以在老年男性中比年轻男性积累更多的突变，因此患有白血病的孩子的父亲可能比没有癌症的孩子的父亲年龄更大。研究方法：急性淋巴细胞白血病（ALL）、急性髓细胞白血病（AML）、神经母细胞瘤或肝母细胞瘤患儿出生时父母的年龄数据由日本儿童癌症登记处提供。以5家医院就诊的患儿家长资料为对照。结果：2 ~ 6岁ALL患儿父母年龄分布曲线完全重叠。ALL患儿父亲和母亲的平均年龄（SD）分别为383.5 ± 67.1个月和348.9 ± 53.3个月。对照组分别为382.6 +/- 65.3和349.4 +/- 54.6。其他年龄段ALL、AML和胚胎性肿瘤（神经母细胞瘤、肾母细胞瘤、肝母细胞瘤）儿童的结果相似。结论：接受检查的癌症儿童的父亲或母亲的年龄之间没有显着差异。老年父母可能在精子或卵子中积累了致癌突变的假设没有得到证实。

项目成果

Kong X-T: "Expression and mutational analysis of the DCC, DPC4 and MADR2 genes in neuroblastoma."Cancer Research. 57. 3772-3778 (1997)

孔X-T：“神经母细胞瘤中DCC、DPC4和MADR2基因的表达和突变分析。”癌症研究。

Guo S-X: "Hypermethylation of p16 and p15 and RB proteint expression in acute leukemia. "Leukemia Research. 24. 39-46 (2000)

郭树新：“急性白血病中p16和p15的高甲基化以及RB蛋白表达。”白血病研究。

X-M.Sheng: "Mutation of the RAS genes in childhood acute myeloid leukemia,myelodysplastic syndvane and juvenile chronic myelocrtic leukemia" Leukemia Research. 21. 697-701 (1997)

盛晓明：“儿童急性髓系白血病、骨髓增生异常综合症和青少年慢性粒细胞白血病中RAS基因的突变”白血病研究。

Yang H-W: "Pattern of FHIT gene expression itc normal and leukemic cells"Int J Cancer. 81. 897-901 (1999)

Yang H-W：“正常细胞和白血病细胞中 FHIT 基因表达的模式”Int J Cancer。

Yang HW: "The p73 gene is less involved in the development but involved in the progression of neuroblastoma."International Journal of Molecular Medicine. 5. 379-384 (2000)

杨红伟：“p73基因较少参与神经母细胞瘤的发生，但参与神经母细胞瘤的进展。”国际分子医学杂志。