儿童癌症成年幸存者的累积烷化剂暴露与精液参数：来自圣裘德终身队列研究的报告。
Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study.
机构信息
Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA; Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN, USA.
出版信息
Lancet Oncol. 2014 Oct;15(11):1215-23. doi: 10.1016/S1470-2045(14)70408-5. Epub 2014 Sep 16.
BACKGROUND
Few data define the dose-specific relation between alkylating agent exposure and semen variables in adult survivors of childhood cancer. We undertook this study to test the hypothesis that increased exposure to alkylating agents would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer.
METHODS
We did semen analysis on 214 adult male survivors of childhood cancer (median age 7·7 years [range 0·01-20·3] at diagnosis, 29·0 years [18·4-56·1] at assessment, and a median of 21·0 years [10·5-41·6] since diagnosis) who had received alkylating agent chemotherapy but no radiation therapy. Alkylating agent exposure was estimated using the cyclophosphamide equivalent dose (CED). Odds ratios (ORs) and 95% CIs for oligospermia (sperm concentration >0 and <15 million per mL) and azoospermia were calculated with logistic regression modelling.
FINDINGS
Azoospermia was noted in 53 (25%) of 214 participants, oligospermia in 59 (28%), and normospermia (sperm concentration ≥15 million per mL) in 102 (48%) participants. 31 (89%) of 35 participants who received CED less than 4000 mg/m(2) were normospermic. CED was negatively correlated with sperm concentration (correlation coefficient=-0·37, p<0·0001). Mean CED was 10 830 mg/m(2) (SD 7274) in patients with azoospermia, 8480 mg/m(2) (4264) in patients with oligospermia, and 6626 mg/m(2) (3576) in patients with normospermia. In multivariable analysis, CED was significantly associated with an increased risk per 1000 mg/m(2) CED for azoospermia (OR 1·22, 95% CI 1·11-1·34), and for oligospermia (1·14, 1·04-1·25), but age at diagnosis and age at assessment were not.
INTERPRETATION
Impaired spermatogenesis was unlikely when the CED was less than 4000 mg/m(2). Although sperm concentration decreases with increasing CED, there was substantial overlap of CED associated with normospermia, oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services.
FUNDING
US National Cancer Institute, American Lebanese Syrian Associated Charities.
背景
关于儿童癌症幸存者的烷基化剂暴露与精液变量之间的剂量特异性关系，仅有少量数据能够定义。我们开展了此项研究，以验证下述假设，即未接受儿童癌症放射治疗的儿童癌症成年男性幸存者中，烷基化剂暴露增加与精子浓度降低有关。
方法
我们对 214 名曾接受烷基化剂化疗但未接受放射治疗的儿童癌症成年男性幸存者（诊断时的中位年龄为 7.7 岁[范围为 0.01-20.3]，评估时的中位年龄为 29.0 岁[18.4-56.1]，诊断后中位时间为 21.0 年[10.5-41.6]）进行了精液分析。使用环磷酰胺等效剂量（CED）估计烷基化剂暴露。使用逻辑回归模型计算少精子症（精子浓度＞0 且＜1500 万/ml）和无精子症的比值比（OR）及其 95%置信区间。
结果
214 名参与者中，53 名（25%）为无精子症，59 名（28%）为少精子症，102 名（48%）为正常精子症（精子浓度≥1500 万/ml）。CED＜4000mg/m2 的 35 名参与者中，有 31 名（89%）为正常精子症。CED 与精子浓度呈负相关（相关系数=-0.37，p＜0.0001）。无精子症患者的平均 CED 为 10830mg/m2（标准差 7274），少精子症患者为 8480mg/m2（4264），正常精子症患者为 6626mg/m2（3576）。多变量分析显示，CED 每增加 1000mg/m2，无精子症的风险比（OR）为 1.22（95%CI 1.11-1.34），少精子症的风险比为 1.14（1.04-1.25），而诊断时的年龄和评估时的年龄则不然。
结论
当 CED 小于 4000mg/m2 时，精子发生受损的可能性较小。虽然随着 CED 的增加精子浓度会降低，但 CED 与正常精子症、少精子症和无精子症之间存在显著重叠。这些数据可以为治疗前患者咨询和生育力保护服务的使用提供信息。
资助
美国国家癌症研究所、美国黎巴嫩叙利亚裔协会慈善基金会。
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