Association of BCG Vaccination in Childhood With Subsequent Cancer Diagnoses A 60-Year Follow-up of a Clinical Trial
Association of BCG Vaccination in Childhood With Subsequent Cancer Diagnoses A 60-Year Follow-up of a Clinical Trial
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DOI：
10.1001/jamanetworkopen.2019.12014
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发表时间：
2019-09-01
影响因子：
13.8
通讯作者：
Aronson, Naomi E.
中科院分区：
文献类型：
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作者：
Usher, Nicholas T.;Chang, Suyoung;Aronson, Naomi E.
重要性 BCG 疫苗是目前唯一获得批准的结核病疫苗，在世界范围内广泛接种，通常在婴儿期接种。先前的研究发现，接种 BCG 的人群中淋巴瘤和白血病的发病率有所增加。 目的 在 BCG 疫苗试验的二次分析中确定 BCG 疫苗接种是否与癌症发病率相关。 设计、设置和参与者 对一项临床试验进行回顾性审查（60 年随访），其中参与者按学区、年龄和性别进行系统分层，然后按轮流随机分配到疫苗组。最初的研究是在 1935 年 12 月至 1998 年 12 月期间在美国 5 个州的 9 个地点进行的。参与者是 2963 名 20 岁以下的美洲印第安人和阿拉斯加原住民学童，没有证据表明既往患有结核病。统计分析于 2018 年 8 月至 2019 年 7 月期间进行。 干预措施 单次皮内注射 BCG 疫苗或生理盐水安慰剂。 主要结果和措施 主要结果是 BCG 疫苗接种后癌症的诊断。还收集了参与者间隔健康和危险因素的数据，包括吸烟、结核感染、异烟肼使用和其他基本人口统计信息。 结果 排除后共有 2963 名参与者，其中卡介苗疫苗组 1540 名，安慰剂组 1423 名。接种疫苗的中位年龄（四分位距）为 8 (5-11) 岁； BCG 组中有 805 名参与者 (52%) 和安慰剂组有 710 名参与者 (50%) 为女性。截至随访时，安慰剂组有 97 名参与者（7%）和卡介苗疫苗组有 106 名参与者（7%）下落不明；安慰剂组的总死亡率为 633 名参与者 (44%)，卡介苗组的总死亡率为 632 名参与者 (41%)。卡介苗疫苗接种者与安慰剂接种者的癌症总体诊断率没有显着差异（风险比，0.82；95% CI，0.66-1.02），包括淋巴瘤和白血病。控制性别、地区、酗酒、吸烟和结核病后，卡介苗接种者的肺癌发病率显着低于安慰剂组（每 10 万人年分别有 18.2 例和 45.4 例；风险比，0.38；95% CI，0.20-0.74；P = 0.005）。 结论和相关性 儿童接种卡介苗与较低的肺癌风险相关美洲印第安人和阿拉斯加原住民的癌症发展。鉴于与肺癌相关的高死亡率和低成本卡介苗疫苗的可用性，这一发现具有潜在的重要健康影响。
IMPORTANCE The BCG vaccine is currently the only approved tuberculosis vaccine and is widely administered worldwide, usually during infancy. Previous studies found increased rates of lymphoma and leukemia in BCG-vaccinated populations.OBJECTIVE To determine whether BCG vaccination was associated with cancer rates in a secondary analysis of a BCG vaccine trial.DESIGN, SETTING, AND PARTICIPANTS Retrospective review (60-year follow-up) of a clinical trial in which participants were assigned to the vaccine group by systematic stratification by school district, age, and sex, then randomized by alternation. The original study was conducted at 9 sites in 5 US states between December 1935 and December 1998. Participantswere 2963 American Indian and Alaska Native schoolchildren younger than 20 years with no evidence of previous tuberculosis infection. Statistical analysis was conducted between August 2018 and July 2019.INTERVENTIONS Single intradermal injection of either BCG vaccine or saline placebo.MAIN OUTCOMES AND MEASURES The primary outcome was diagnosis of cancer after BCG vaccination. Data on participant interval health and risk factors, including smoking, tuberculosis infection, isoniazid use, and other basic demographic information, were also collected.RESULTS A total of 2963 participants, including 1540 in the BCG vaccine group and 1423 in the placebo group, remained after exclusions. Vaccination occurred at a median (interquartile range) age of 8 (5-11) years; 805 participants (52%) in the BCG group and 710 (50%) in the placebo group were female. At the time of follow-up, 97 participants (7%) in the placebo group and 106 participants (7%) in the BCG vaccine group could not be located; total mortality was 633 participants (44%) in the placebo group and 632 participants (41%) in the BCG group. The overall rate of cancer diagnosis was not significantly different in BCG vaccine vs placebo recipients (hazard ratio, 0.82; 95% CI, 0.66-1.02), including for lymphoma and leukemia. The rate of lung cancer was significantly lower in BCG vs placebo recipients (18.2 vs 45.4 cases per 100 000 person-years; hazard ratio, 0.38; 95% CI, 0.20-0.74; P =.005), controlling for sex, region, alcohol overuse, smoking, and tuberculosis.CONCLUSIONS AND RELEVANCE Childhood BCG vaccination was associated with a lower risk of lung cancer development in American Indian and Alaska Native populations. This finding has potentially important health implications given the high mortality rate associated with lung cancer and the availability of low-cost BCG vaccines.