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June 21, 2006 (亚特兰大) — 根据在第42届美国临床肿瘤学会年会所发表的初步研究发现，基因改变或许可以解释，当某些孩童接受anthracycline化疗后10到15年发生心脏问题的原因。
宾州大学的研究者从美国国家健康研究院进行的孩童癌症存活大型调查搜集而来的资料中，比较发生CHF者和未发生的相对对照组。
他们起先发现有47位CHF病患和195位控制组（书面摘要中所报告），但是在年会中口头发表时，则是报告有27位CHF病患和99位控制组；主要作者Richard Aplenc医师解释这是因为他的团队决定将数据限定在白种人，以排除任何可能因种族上的潜在基因不同之影响因素；Aplenc医师是宾州大学医学院儿科助理教授。
该团队完成7个基因的10种基因多形性基因定型，包括anthracyclines和氧自由基之代谢自导基因；Aplenc医师解释这是根据此一领域的最新思维，就是假设anthracyclines引起的心脏损伤发生于两个步骤：早期损伤是因为不活性的氧自由基所致，慢性毒性则是anthracycline酒精代谢物所引起。
该团队发现特定的多型性基因改变和发生CHF的风险大小有关，包括GSTP 和CBR3等基因的特定突变。
Aplenc医师在发布新闻时表示，我们无法因此一研究即说我们足以开始测试这些病患，重要的是我们要研究更多的病患以及探究其他基因多形性。
他进一步补充，我们的希望是有朝一日可以用此类资讯帮助决定治疗方式，以及决定哪些癌症存活者需要更加注意治疗后可能发生心脏问题。
同样来自宾州大学的Anna Meadows 医师在年会中的另一段讨论会时提出，在孩童的治愈率越获改善时，对孩童期化疗迟发性并发症建立生物标记更是一大挑战。
Meadows医师并未参与该研究。
Genetic Clues to Cardiac Damage From Anthracyclines
By Zosia Chustecka
Medscape Medical News
June 21, 2006 (Atlanta) — Genetic variations may explain while some children who receive anthracycline chemotherapy develop cardiac problems later in life, typically 10 to 15 years after treatment has finished, according to preliminary findings reported at the recent 42nd annual meeting of the American Society of Clinical Oncology .
Using data collected from the large Childhood Cancer Survivor Study, which is supported by the US National Institutes of Health, researchers from the University of Pennsylvania, in Philadelphia, compared a group of patients who went on to develop congestive heart failure (CHF) with a matched control group who did not.
Initially they found 47 patients with CHF and 195 controls (as reported in the abstract), but in the oral presentation at the meeting, the numbers were reported as 27 patients with CHF and 99 controls. Lead author Richard Aplenc, MD, explained that his team had decided to restrict the data to white subjects to eliminate any potential confounding influence of ethnic genetic variation. Dr. Aplenc is an assistant professor of pediatrics at the University of Pennsylvania School of Medicine.
The team carried out genotyping for 10 genetic polymorphisms in 7 genes, homing in on genes involved in the metabolism of anthracyclines and free oxygen radicals. Dr. Aplenc explained that this focus was guided by the latest thinking in this field, which hypothesizes that cardiac damage from anthracyclines occurs in a 2-step process, with early damage caused by reactive oxygen free radicals, while chronic toxicity is mediated by anthracycline alcohol metabolites.
The team found specific polymorphic genetic variants that appear to modify the risk of developing CHF, including specific mutations in the GSTP and CBR3 genes.
"We can't say based on this study that we're ready to start testing patients for these variations," Dr. Aplenc commented in a news release. "We need to look at more patients and look for additional polymorphisms that may be important."
"However, our hope is that one day we might use this type of information to guide treatment decisions and to determine which cancer survivors should be more closely monitored for cardiac problems in the years following treatment," he added.
"Identifying biomarkers for delayed complications of childhood chemotherapy is a major challenge as the cure rate continues to improve in children," commented Anna Meadows, MD, also from the University of Pennsylvania, speaking at another session during the meeting. Dr. Meadows was not involved in this study.
ASCO 42nd Annual Meeting: Abstract 9004. Presented June 3, 2006.