Infectious Diseases Division, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
College of Agriculture and Life Sciences, Cornell University, Ithaca, New York.
JAMA Netw Open. 2019 Sep 4;2(9):e1912014. doi: 10.1001/jamanetworkopen.2019.12014.
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.
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. Participants were 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.
Single intradermal injection of either BCG vaccine or saline placebo.
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.
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.
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.
卡介苗是目前唯一获得批准的结核病疫苗，在全球范围内广泛使用，通常在婴儿期接种。先前的研究发现，卡介苗接种人群中淋巴瘤和白血病的发病率增加。
在卡介苗疫苗试验的二次分析中，确定卡介苗接种是否与癌症发病率有关。
设计、地点和参与者：对一项临床试验进行回顾性分析（60 年随访），参与者按学区、年龄和性别进行系统分层分配到疫苗组，然后通过交替进行随机分组。最初的研究于 1935 年 12 月至 1998 年 12 月在美国 5 个州的 9 个地点进行。参与者为 2963 名年龄在 20 岁以下的美国印第安人和阿拉斯加原住民学龄儿童，无既往结核病感染证据。统计分析于 2018 年 8 月至 2019 年 7 月进行。
皮内单次注射卡介苗或生理盐水安慰剂。
主要结局是卡介苗接种后的癌症诊断。还收集了参与者间隔期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学信息。
排除后，共有 2963 名参与者，包括卡介苗组 1540 名和安慰剂组 1423 名。接种疫苗的中位（四分位间距）年龄为 8 岁（5-11 岁）；卡介苗组 805 名（52%）和安慰剂组 710 名（50%）为女性。随访时，安慰剂组有 97 名（7%）参与者和卡介苗组有 106 名（7%）参与者无法找到；安慰剂组总死亡率为 633 名（44%），卡介苗组为 632 名（41%）。卡介苗组和安慰剂组癌症诊断的总体发生率无显著差异（风险比，0.82；95%CI，0.66-1.02），包括淋巴瘤和白血病。与安慰剂组相比，卡介苗组肺癌发生率显著降低（每 100000 人年 18.2 例与 45.4 例；风险比，0.38；95%CI，0.20-0.74；P = 0.005），控制了性别、地区、酒精滥用、吸烟和结核。
儿童期卡介苗接种与美国印第安人和阿拉斯加原住民人群肺癌发病风险降低相关。鉴于肺癌死亡率高且卡介苗疫苗价格低廉，这一发现具有潜在的重要健康意义。
