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儿童期和青年期被诊断患有癌症的男性的为人父母情况:丹麦全国队列研究中的随时间变化趋势。

Parenthood among men diagnosed with cancer in childhood and early adulthood: trends over time in a Danish national cohort.

机构信息

Department of Obstetrics and Gynaecology, Fertility Clinic Section 455, Hvidovre University Hospital, Hvidovre, Copenhagen, Denmark.

Department of Public Health, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Hum Reprod. 2021 Aug 18;36(9):2576-2586. doi: 10.1093/humrep/deab154.

Abstract

STUDY QUESTION

Is the rate of fatherhood among men diagnosed with cancer in childhood and early adulthood different from men without cancer, and, if so, have the differences changed over time?

SUMMARY ANSWER

Men diagnosed with cancer have had significantly reduced rates of fatherhood compared with undiagnosed men; however, the rates of fatherhood among the cancer survivors have increased markedly over time.

WHAT IS KNOWN ALREADY

The number of children and young adolescents who survive cancer has steadily increased over recent decades, with a current 5-year survival rate of approximately 80%. Consequently, life circumstances after cancer have gained increasing importance, including the desire among survivors to have children and a family. ARTs to aid reproduction among cancer survivors have been developed, and fertility preservation is increasingly a topic being discussed before undergoing cancer treatment. But the potential for fertility preservation differs dependent on age at diagnosis and type of cancer. Earlier studies have shown a decreased fertility rate among survivors of child and adolescent cancer compared to those diagnosed in early adulthood.

STUDY DESIGN, SIZE, DURATION: This study is a national, register-based cohort study. Men diagnosed with cancer in childhood and early adulthood (<30 years of age) were registered in the Danish Cancer Register in 1978-2016 (n = 9353). According to the time of diagnosis, each cancer-diagnosed man was randomly matched with 150 undiagnosed men from the background population within the same birth year. The men were followed until having their first child, death, migration or the end of the study (31 December 2017) in medical registers and socio-demographic population registers.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Fatherhood among the boys and young men diagnosed with cancer were compared with the age-matched comparison group in all statistical analyses. Cancer diagnoses were categorised as central nervous system (CNS) cancers, haematological cancers or solid cancers. Analyses were stratified by age at diagnosis (0-9, 10-19, 20-29 years) and time of diagnosis (1978-1989, 1990-1999, 2000-2009, 2010-2016). Death was incorporated as a competing risk in all analyses.

MAIN RESULTS AND THE ROLE OF CHANCE

The study population consisted of 9353 boys and young men diagnosed with cancer between 1978 and 2016 and 1 386 493 men in the age-matched comparison group. Those surviving CNS cancer as young men had the lowest hazard ratio (HR) of fatherhood compared with the age-matched comparison group (HR 0.67, 95% CI 0.57-0.79), followed by survivors of haematological cancers (HR 0.90, 95% CI 0.81-1.01), while the highest chance of fatherhood was among survivors of solid cancers (HR 1.16, 95% CI 1.12-1.20) with a slightly increased HR compared with undiagnosed males. The HR of becoming a father increased over time. From the first decade to the last decade 30 years later, the HR of becoming a father increased for solid tumours (HR 0.78, 95% CI 0.73-0.83 to HR 1.08, 95% CI 0.95-1.22), haematological cancers (HR 0.64, 95% CI 0.53-0.79 to HR 0.97, 95% CI 0.73-1.30) and CNS cancers (HR 0.44, 95% CI 0.34-0.57 to HR 0.98, 95% CI 0.49-1.95) compared to the age-matched comparison group. Also, when compared with the age-matched comparison group, men diagnosed with cancer when aged 20-29 years were more likely became fathers over the time of the study (HR 0.80, 95% CI 0.74-0.86 to HR 1.08, 95% CI 0.96-1.22).

LIMITATIONS, REASONS FOR CAUTION: The study was based on register data, and information was not available about the men's fertility potential, whether they had a desire to have children and whether it was possible for them to find a partner. Information about fertility preservation, e.g. sperm freezing, could also have provided additional insights. Furthermore, information about diagnosis and ART treatment would have been beneficial.

WIDER IMPLICATIONS OF THE FINDINGS

Information and education of male patients diagnosed with cancer about fertility preservation options and their chances to create their own family is crucial. Reassuringly, time trends showed more men with a previous cancer diagnosis becoming fathers in recent years than in earlier years, reflecting that survival and fertility preservation have improved over time.

STUDY FUNDING/COMPETING INTEREST(S): R.S. received a PhD grant from the Rosa Ebba Hansen Foundation and from the Health Foundation (J.nr. 15-B-0095). The funding for the establishment of the DANAC II Cohort was obtained from the Rosa Ebba Hansen Foundation. The authors have no conflicts of interest to declare.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

在儿童和成年早期被诊断患有癌症的男性与未患癌症的男性相比,其成为父亲的比例是否不同?如果不同,这种差异是否随时间而变化?

总结答案

与未被诊断的男性相比,被诊断患有癌症的男性成为父亲的比例明显降低;然而,癌症幸存者成为父亲的比例随着时间的推移显著增加。

已知情况

近几十年来,存活的儿童和青少年癌症患者数量稳步增加,目前 5 年生存率约为 80%。因此,癌症治疗后的生活环境变得越来越重要,包括幸存者想要孩子和家庭的愿望。已经开发出辅助癌症幸存者生育的辅助生殖技术,并且在接受癌症治疗之前,越来越多地讨论生育保护问题。但是,生育保护的潜力取决于诊断时的年龄和癌症类型。早期研究表明,与成年早期被诊断为癌症的幸存者相比,儿童和青少年癌症幸存者的生育能力下降。

研究设计、规模、持续时间:本研究是一项全国性的基于登记的队列研究。1978 年至 2016 年,在丹麦癌症登记处登记了儿童和成年早期(<30 岁)被诊断为癌症的男性(n=9353)。根据诊断时间,每个癌症诊断的男性被随机与同一年出生的背景人群中的 150 名未被诊断的男性匹配。这些男性在医疗记录和社会人口登记册中,直至首次生育、死亡、移民或研究结束(2017 年 12 月 31 日)。

参与者/材料、设置、方法:在所有统计分析中,将患有癌症的男孩和年轻男性与年龄匹配的对照组进行比较。癌症诊断分为中枢神经系统(CNS)癌症、血液癌症或实体癌症。分析按诊断年龄(0-9 岁、10-19 岁、20-29 岁)和诊断时间(1978-1989 年、1990-1999 年、2000-2009 年、2010-2016 年)进行分层。死亡被纳入所有分析作为竞争风险。

主要结果和机会的作用

该研究人群包括 1978 年至 2016 年间被诊断为癌症的 9353 名男孩和年轻男性,以及年龄匹配的对照组中的 1386493 名男性。与年龄匹配的对照组相比,患有中枢神经系统癌症的年轻男性成为父亲的风险比(HR)最低(HR 0.67,95%CI 0.57-0.79),其次是血液癌症幸存者(HR 0.90,95%CI 0.81-1.01),而实体癌症幸存者的生育能力最高(HR 1.16,95%CI 1.12-1.20),与未被诊断的男性相比,风险比略有增加。成为父亲的几率随着时间的推移而增加。从第一个十年到 30 年后的最后一个十年,实体肿瘤(HR 0.78,95%CI 0.73-0.83 至 HR 1.08,95%CI 0.95-1.22)、血液癌症(HR 0.64,95%CI 0.53-0.79 至 HR 0.97,95%CI 0.73-1.30)和中枢神经系统癌症(HR 0.44,95%CI 0.34-0.57 至 HR 0.98,95%CI 0.49-1.95)的成为父亲的几率相对于年龄匹配的对照组有所增加。此外,与年龄匹配的对照组相比,被诊断为 20-29 岁癌症的男性在研究期间更有可能成为父亲(HR 0.80,95%CI 0.74-0.86 至 HR 1.08,95%CI 0.96-1.22)。

局限性、谨慎的原因:该研究基于登记数据,并且没有关于男性生育能力的信息,也没有关于他们是否有生育孩子的愿望以及他们是否有可能找到伴侣的信息。关于生育保护的信息,例如精子冷冻,也可以提供更多的见解。此外,有关诊断和辅助生殖技术(ART)治疗的信息将是有益的。

研究结果的更广泛意义

向被诊断患有癌症的男性提供有关生育保护选择及其创造自己家庭的机会的信息和教育至关重要。令人欣慰的是,随着时间的推移,越来越多的患有先前癌症诊断的男性成为父亲,这反映出生存和生育保护随着时间的推移而得到改善。

研究资助/利益冲突:R.S. 从罗莎·埃芭·汉森基金会和健康基金会(J.nr. 15-B-0095)获得了博士奖学金。DANAC II 队列的建立资金来自罗莎·埃芭·汉森基金会。作者没有利益冲突需要申报。

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