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形态学异常与儿童癌症高风险有关

来源:医源世界
摘要:根据一项发表于1月2日美国医学会期刊的研究数据显示,儿童癌症病患形态异常的盛行率显著高于控制组,罹患癌症儿童有单一与合并形态异常的高发生率,显示体质上的基因缺失,在儿童癌症发生上比目前所估计的扮演更重要的角色。主要作者荷兰阿姆斯特丹Emma儿童医院学术医学中心H。9%儿童癌症病患中,被确定诊断有临床基因症......

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  January 3, 2008 — 根据一项发表于1月2日美国医学会期刊的研究数据显示,儿童癌症病患形态异常的盛行率显著高于控制组,罹患癌症儿童有单一与合并形态异常的高发生率,显示体质上的基因缺失,在儿童癌症发生上比目前所估计的扮演更重要的角色。
  
  主要作者荷兰阿姆斯特丹Emma儿童医院学术医学中心H. M. Merks医师向Medscape肿瘤学表示,在3.9%儿童癌症病患中,被确定诊断有临床基因症候群的比例比一般大众高很多,尽管密集的一般儿童病患照护,仍然有一半的症候群是被遗漏的,表示所有的儿童癌症病患应该由临床基因学家或接受临床形态学评估训练的小儿科医师进行评估。
  
  作者表示,肿瘤形成的高风险过去已被发现与临床基因症候群有关,在这些症候群中,体质上的基因缺失会导致病患易发生特定癌症的临床基因型。
  
  儿童癌症与重大畸形,因为重大畸形的低盛行率而难以确认;体外基因型的分析将会需要对每位病患进行完整的检查,且尽管已有这样的临床研究,但它们的样本数目是很小的,且因不一致的定义与分类而受阻碍。
  
  在这项研究中,Merks医师与其同事进行一项研究,于2000年1月到2003年3月之间,评估1073位儿童癌症病患的形态异常,所有病患都接受针对683种形态异常的身体检查;1007位健康儿童作为控制组,以同样的方式进行检查。
  
  他们发现,罹患癌症儿童的重大畸形与轻微异常盛行率显著高于控制组;在每1000个个案中,癌症儿童病患有268位有重大畸形,而控制组仅有155位有重大畸形;儿童癌症患者有合并重大畸形或是轻微畸形的发生率显著较高,26.8%个体病患有一个以上的重大畸形,控制组则是15.5%;癌症病患中有5.1%有两个以上的重大畸形、控制组则是1.6%,而0.9%癌症病患有三个以上的重大畸形、至于控制组则没有任何人有此情形。
  
  当针对轻微畸型时,研究者表示,65.1%癌症病患有一个以上的轻微畸型、控制组则是56.2%;32.8%癌症病患有两个以上的轻微畸型、控制组则是22.1%;15.2%的癌症病患与8.3%的控制组个体有三个以上的轻微畸型;42位(3.9%)病患有已确立的临床基因症候群。当进行多变项分析时,结果显示病患组发生14种形态学异常的比例显著较高;以眼睑裂缝狭小与不对称下肢,这两个形态异常同时发生的情况更为常见,暗示这可能是倾向发生新肿瘤的症候群。
  
  虽然这两种异常形态并没有与特定癌症有相关性,但在发生不对称下肢症候群的性别上有显著差异,因为这大多发生在男性身上,这倾向肿瘤发生症候群可能是X染色体性联遗传
  
  Merk医师解释,他们现在必须在另一个独立群体中确认这两个新的倾向肿瘤发生症候群;Merk医师表示,尽快在另一个独立样本上确认,我们就可以估计该症候群在一般大众身上的发生率。
  
  他指出,他们也必须找出导致临床形态学表现型、以及共同使病患倾向发展出特定癌症的基因缺陷;一旦找到基因缺失,他们就可以用于早期诊断个体病患是否罹患这样的症候群;如果散发性肿瘤也有同样的基因缺失,这可以用于改善肿瘤诊断,且或许可以用于研发新的治疗药物。
  
  然而,他提醒这仍然在推测的阶段,因为目前为止尚未找到这基因缺失。
  
  这项研究部分由荷兰阿姆斯特丹儿童癌症研究基金会(Stichting Kindergeneeskundig Kankeronderzoek)赞助。

Morphologic Abnormalities Associated With Higher Risk of Childhood Cancer

 

By Roxanne Nelson
Medscape Medical News


January 3, 2008 — Pediatric cancer patients have a significantly higher prevalence of morphologic abnormalities than controls, researchers report. According to data that appear in the January 2 issue of the Journal of the American Medical Association, children with cancer were shown to have a high incidence of both of single and combined morphologic abnormalities, suggesting that constitutional genetic defects play a more important role in pediatric oncogenesis than is currently estimated.

"In 3.9% of pediatric cancer patients, an established clinical genetic syndrome is diagnosed, which is much higher than in the general population," lead author Johannes H. M. Merks, MD, PhD, from Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands, told Medscape Oncology. "Half of the syndromes were missed despite intensive general pediatric care, indicating that all childhood cancer patients deserve an evaluation by a clinical geneticist or pediatrician trained in clinical morphology."

A higher risk of tumor development was previously associated with clinical genetic syndromes and, within these syndromes, the constitutional molecular defects that lead to the clinical phenotype that predisposed the patient to develop specific cancers are the same, the authors note.

Associations between pediatric cancers and major malformations are difficult to identify because of the low prevalence of major malformations. An analysis of external phenotypes would require a thorough clinical examination of every patient, and although this type of clinical trial has been conducted, they have generally been small and hindered by highly variable terminology and classification.

In this study, Dr. Merks and colleagues conducted a study to assess the prevalence of morphologic abnormalities in 1073 pediatric cancer patients between January 2000 and March 2003. All patients underwent a physical examination that was directed at 683 morphologic abnormalities; the1007 healthy children who served as controls were examined in an identical manner.

They found that major abnormalities and minor anomalies were significantly more prevalent among patients with cancer than among controls. In every 1000 cases, there were 268 major abnormalities among pediatric cancer patients and 155 among the control group. The pediatric cancer patients also had a significantly higher occurrence of combinations of major abnormalities or minor anomalies. One or more major abnormalities were observed in 26.8% of individual patients, compared with 15.5% of controls. Two or more major abnormalities were present in 5.1% of cancer patients and 1.6% of controls, and 3 or more abnormalities were found in 0.9% of patients and none of the controls.

When looking at minor abnormalities, the researchers noted that 1 or more minor anomalies were found in 65.1% of individual patients and 56.2% of controls; 2 or more minor anomalies were found in 32.8% of patients and 22.1% of controls; and 3 or more minor anomalies were found in 15.2% of patients and 8.3% of controls. An established clinical genetic syndrome was identified in 42 patients (3.9%). When a multivariate analysis was performed, results showed that 14 morphologic abnormalities occurred at a significantly higher rate in the patient group. For blepharophimosis and asymmetric lower limbs, statistically significant patterns of co-occurring morphologic abnormalities were identified, suggestive of new tumor predisposition syndromes. Although neither of the 2 patterns was significantly associated with a particular type of cancer, there was a significant difference in gender for the asymmetric lower limbs syndrome. Because it was predominant in males, this tumor predisposition syndrome might be X-linked.

Dr. Merks explained that they now have to confirm the 2 new tumor predisposition syndromes in an independent cohort. "As soon as they have been confirmed in an independent sample, we can estimate the incidence of the syndromes in the general population," said Dr. Merks.

They also need to identify the underlying genetic defects that lead to the clinical morphologic phenotypes and concurrently predispose the patients to develop specific cancers. "Once the genetic defects have been identified, they could be used for early diagnosis of the syndrome in individual patients," he said. "If the same gene defects would occur in sporadic tumors, this could be used for improved tumor diagnosis and perhaps for targeting new therapeutic agents."

However, he cautioned that this is still quite speculative because the underlying defects have not yet been identified.

This research was partly funded by the Foundation of Pediatric Cancer Research (Stichting Kindergeneeskundig Kankeronderzoek), Amsterdam, the Netherlands.

JAMA. 2008;299:61-69. Abstract


 

作者: 佚名 2008-3-26
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