Can we now vaccinate against lung cancer?

Not so fast.  The report below suggests that we can but it is misleading.

The story starts with a remarkable product that originated in the early 20th century: BCG vaccine. Some patient French scientists produced a weakened bacillus from the form of tuberculosis that cattle get. They used their product as an effective vaccine against TB for humans. It is actually a live bacterium that they and their successors inject into you as a vaccination. But it is a real life-saver. Once injected with it, you mostly don't get TB at all and you mostly recover well in a worst case scenario. It is very widely used so it keeps a large lot of Third-worlders alive.

So is it itself dangerous to your health?  The studies of that differ in their conclusions but the general conclusion is that it is pretty safe.  The study below aimed to settle that for once and for all.  And it did.  With a follow-up of thousands of people across a remarkable 60 year period, people who had been given the vaccine were no more likely to die than anyone else.  You seldom get conclusions as solid as that.

While analysing their data however the authors noticed something interesting. There were a lot fewer lung cancer deaths among those who had received the BCG vaccine.  They cried Eureka and said we now know how to prevent lung cancer.  They were able to show statistical significance for their findings so that is that!

But it isn't. The effect they found is exceptionally small statistically (a hazard ratio of 0.38) and was shown as statistically significant only because of the large sample size.  It has no precedent so is clearly one of those adventitious findings that you often get when analysing a large and complex body of data:  Findings that will never emerge again.

Because you can do it so easily, it is actually regarded as bad science to report such adventitious findings. You are supposed to report the significance or not of only those correlations you have predicted from theory. A lot of last minute theory revisions happen of course.

So all the work behind that study was well-justified by the findings that BCG -- as predicted -- is very safe but the "findings" about lung cancer should be ignored.

Association of BCG Vaccination in Childhood With Subsequent Cancer Diagnoses: A 60-Year Follow-up of a Clinical Trial

Nicholas T. Usher et al.


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. 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.

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 = less than .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.

JAMA Netw Open. 2019;2(9):e1912014. doi:10.1001/jamanetworkopen.2019.12014

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