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JAMA 子刊｜母乳喂养时间与儿童癌症风险降低有关

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撰文｜陈灵珺      责编｜周叶斌
在欧洲，15岁以下儿童中每350人就有1人患癌，癌症是仅次于婴儿期死亡的主要疾病相关死亡原因。尽管至少10%的儿童癌症与罕见的种系突变有关，大多数儿童癌症的病因仍不明确，目前也没有确立的预防措施。
新兴研究表明，母乳喂养可能与儿童癌症风险降低有关，尤其是急性淋巴细胞白血病（ALL）。一些荟萃分析和汇总研究显示，母乳喂养至少6个月的儿童患ALL或白血病的风险比喂养时间较短或未喂养的儿童低约20%。此外，一些研究还发现母乳喂养与急性髓性白血病（AML）、霍奇金淋巴瘤和神经母细胞瘤风险降低有关。母乳喂养对儿童ALL的保护作用有一定的生物学依据，因为母乳喂养在婴儿肠道微生物群和免疫系统的形成中起关键作用。免疫反应异常被认为在儿童B细胞前体（BCP）ALL的发展中起重要作用。一些动物模型研究也表明，复杂且丰富的微生物群能够保护对抗BCP-ALL的发生。
近日，丹麦联合研究团队在 JAMA Network Open 发表了题为 Exclusive Breastfeeding Duration and Risk of Childhood Cancers 的文章，揭示了较长的纯母乳喂养持续时间（即至少3个月）与儿童B细胞前体急性淋巴细胞白血病（BCP- ALL）风险降低有关。这些发现提示母乳喂养不仅可能通过生物途径调节儿童癌症风险，还可能作为一种简单的预防措施。

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该研究获取了超过30万名儿童纯母乳喂养持续时间的信息。Signe Holst Søegaard博士团队基于丹麦国家儿童健康登记处（DNCHR）的行政记录开展了一项基于登记的队列研究，调查了2005年至2018年期间丹麦出生儿童的纯母乳喂养持续时间与儿童风险直接的关系。

最新研究发现，较长的纯母乳喂养持续时间与儿童白血病的风险降低相关。这项基于丹麦人群的研究纳入了309,473名儿童，结果显示，纯母乳喂养至少3个月与血液系统肿瘤的风险显著降低，特别是B细胞前体型白血病（BCP-ALL）的风险降低。然而，纯母乳喂养持续时间与中枢神经系统肿瘤和实体肿瘤的风险无关。

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表1.整个队列相比，确诊为癌症的儿童不太可能是家中的第一个孩子，出生时体重也较高。此外，与整个队列中的儿童相比，患有ALL的儿童分娩时母亲年龄在35岁或以上的可能性更大。
在研究期间，共有309,473名儿童被纳入分析，其中0.1%（332名）儿童在1至14岁时被诊断为癌症。与纯母乳喂养不足3个月相比，纯母乳喂养持续3个月或更长时间与血液系统肿瘤的风险显著降低（调整风险比为0.66，95%置信区间为0.46-0.95），这主要归因于对B细胞前体型白血病的风险降低（调整风险比为0.62，95%置信区间为0.39-0.99）。然而，纯母乳喂养持续时间与中枢神经系统肿瘤（调整风险比为0.96，95%置信区间为0.51-1.88）和实体肿瘤（调整风险比为0.87，95%置信区间为0.55-1.41）的风险无关。

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表2. 列出了额外 1 个月纯母乳喂养与癌症风险关联的对数线性趋势 HRs。虽然大多数受 调查癌症的 HR 值接近 1，但血液系统癌症的对数线性趋势调整 HR 值(AHR)总体为 0.91( 95% CI，0.83-0.99)，BCP-ALL 为 0.90(95% CI，0.80-1.01)。
这项研究表明较长的纯母乳喂养持续时间可能是预防儿童B细胞前体型急性淋巴细胞白血病的潜在因素。研究建议继续深入研究观察到的关联背后的生物学机制，以为未来的干预措施提供信息。
母乳喂养对婴儿肠道微生物群和免疫系统的塑造具有重要作用，因此母乳喂养可能通过这些生物学机制对B细胞前体型白血病的发生起到保护作用。这项研究的结果有助于指导未来的干预措施，继续研究在这一关联中的潜在生物学机制。母乳喂养持续时间的延长可能成为预防儿童B细胞前体型白血病的重要因素。

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排版 | Sheila   校对 | uu

*本文由深圳市拾玉儿童公益基金会“儿童肿瘤前沿”团队编译或约稿，文中图表均源引自文献原文。本文著作权归文章作者所有，欢迎个人转发分享，未经允许禁止转载，作者拥有所有法定权利，违者必究。如需转载，请留言或联系[email protected]。本文旨在分享儿童肿瘤科研前沿成果，不是治疗方案推荐。如需获得疾病治疗方案指导，请前往正规医院就诊。

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原文摘要（Abstract）

Importance: Breastfeeding has been suggested to protect against childhood cancers, particularly acute lymphoblastic leukemia (ALL). However, the evidence stems from case-control studies alone.

Objective: To investigate whether longer duration of exclusive breastfeeding is associated with decreased risk of childhood ALL and other childhood cancers.

Design, setting, and participants: This population-based cohort study used administrative data on exclusive breastfeeding duration from the Danish National Child Health Register. All children born in Denmark between January 2005 and December 2018 with available information on duration of exclusive breastfeeding were included. Children were followed up from age 1 year until childhood cancer diagnosis, loss to follow-up or emigration, death, age 15 years, or December 31, 2020. Data were analyzed from March to October 2023.

Exposure: Duration of exclusive breastfeeding in infancy.

Main outcomes and measures: Associations between duration of exclusive breastfeeding and risk of childhood cancer overall and by subtypes were estimated as adjusted hazard ratios (AHRs) with 95% CIs using stratified Cox proportional hazards regression models.

Results: A total of 309 473 children were included (51.3% boys). During 1 679 635 person-years of follow-up, 332 children (0.1%) were diagnosed with cancer at ages 1 to 14 years (mean [SD] age at diagnosis, 4.24 [2.67] years; 194 boys [58.4%]). Of these, 124 (37.3%) were diagnosed with hematologic cancers (81 [65.3%] were ALL, 74 [91.4%] of which were B-cell precursor [BCP] ALL), 44 (13.3%) with central nervous system tumors, 80 (24.1%) with solid tumors, and 84 (25.3%) with other and unspecified malignant neoplasms. Compared with exclusive breastfeeding duration of less than 3 months, exclusive breastfeeding for 3 months or longer was associated with a decreased risk of hematologic cancers (AHR, 0.66; 95% CI, 0.46-0.95), which was largely attributable to decreased risk of BCP-ALL (AHR, 0.62; 95% CI, 0.39-0.99), but not with risk of central nervous system tumors (AHR, 0.96; 95% CI, 0.51-1.88) or solid tumors (AHR, 0.87; 95% CI, 0.55-1.41).

Conclusions and relevance: In this cohort study, longer duration of exclusive breastfeeding was associated with reduced risk of childhood BCP-ALL, corroborating results of previous case-control investigations in this field. To inform future preemptive interventions, continued research should focus on the potential biologic mechanisms underlying the observed association.

DOI: 10.1001/jamanetworkopen.2024.3115

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