Department of Pediatrics, Lund University and Skåne University Hospital, Malmö, Sweden.
Clin Cancer Res. 2010 Aug 1;16(15):3843-50. doi: 10.1158/1078-0432.CCR-10-0140. Epub 2010 Jun 2.
It is not known whether childhood cancer and its treatment are associated with sperm DNA damage, which subsequently affects fertility and might be transmitted to the offspring. The aim of this study is to assess DNA fragmentation index (DFI) as an indicator of sperm DNA integrity in childhood cancer survivors (CCS), with treatment regimen taken into account.
In 99 CCS and 193 age-matched healthy controls, DFI was assessed by using sperm chromatin structure assay.
In the whole group of CCS, DFI was increased compared with the controls, with borderline statistical significance [mean difference, 1.8%; 95% confidence interval (95% CI), -0.0088%-3.7%]. Those treated with radiotherapy only (mean difference, 6.0%; 95% CI, 1.6-10%) or surgery only (mean difference, 2.9%; 95% CI, 0.083-5.8%) had statistically significantly higher DFI than the controls. The odds ratio (OR) for having DFI >20%, which is associated with reduced fertility, was significantly increased in CCS compared with the control group (OR, 2.2; 95% CI, 1.1-4.4). For the radiotherapy-only group, the OR was even higher (OR, 4.9; 95% CI, 1.3-18). DFI was not associated with dose of scattered testicular irradiation or type of chemotherapy given.
DFI was increased in CCS, with those treated with chemotherapy being the only exception. This sperm DNA impairment may be associated with the disease per se rather than due to the treatment, and may have negative consequences in terms of fertility and risk of transmission to the offspring.
目前尚不清楚儿童癌症及其治疗是否会导致精子 DNA 损伤,进而影响生育能力,并可能遗传给后代。本研究旨在评估 DNA 碎片化指数(DFI)作为儿童癌症幸存者(CCS)精子 DNA 完整性的指标,并考虑治疗方案。
在 99 名 CCS 和 193 名年龄匹配的健康对照者中,使用精子染色质结构检测评估 DFI。
在整个 CCS 组中,DFI 与对照组相比有所增加,具有边界统计学意义[平均差异,1.8%;95%置信区间(95%CI),-0.0088%-3.7%]。仅接受放疗(平均差异,6.0%;95%CI,1.6-10%)或仅接受手术(平均差异,2.9%;95%CI,0.083-5.8%)的患者 DFI 明显高于对照组。与生育力降低相关的 DFI>20%的 CCS 患者的比值比(OR)明显高于对照组(OR,2.2;95%CI,1.1-4.4)。对于仅接受放疗的组,OR 甚至更高(OR,4.9;95%CI,1.3-18)。DFI 与散在睾丸照射剂量或给予的化疗类型无关。
CCS 的 DFI 增加,而接受化疗的患者是唯一的例外。这种精子 DNA 损伤可能与疾病本身有关,而不是由于治疗引起的,可能对生育能力和遗传给后代的风险产生负面影响。