Efficacy of BCG vaccination in prevention of cancer: an update. Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: a Danish case-cohort study. BCG vaccination and the subsequent development of cancer in humans. Newborns develop a Th1-type immune response to Mycobacterium bovis bacillus Calmette-Guérin vaccination.
From 1949 to 1951 , a controlled trial of BCG vaccinations was conducted in Puerto Rico . The 191,827 children , 1 - 18 years of age , initially enrolled in the study were skin-tested with tuberculin to determine their eligibility for vaccination . A total of 82,269 children were classified as reactors and not vaccinated . Of the 109 , 558 nonreactors , 31,586 refused vaccination  , 50,634 were vaccinated with BCG  , and 27,338 were left unvaccinated as controls . We ascertained the incidence of cancer over an average follow-up period of 23.3 years in the latter two groups using the Puerto Rico Central Cancer Registry . By the end of December 1973 , a total of 77 cancers had been diagnosed among the controls and 150 among the vaccinees . The overall incidence of cancer among the two groups was similar . Although a number of differences existed between the vaccinee group and the controls in regard to the incidence of cancer at various " sites " , none of these differences was statistically significant . However , when cases of lymphosarcoma and Hodgkin 's disease were combined for analysis , a statistically significant excess of cases occurred among the vaccinees . We concluded that BCG vaccination had no protective effect on the subsequent development of cancer in this population . The slight excess of cases of lymphosarcoma and Hodgkin 's disease among the vaccinees raised the possibility that BCG may have had an adverse effect Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries . The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines . In a background cohort ( N=47,622 ) from the Copenhagen School Health Records Register , cases of leukaemia ( N=20 ) and lymphoma ( N=51 ) were identified through the Danish Cancer Registry . The vaccination status of the cases was compared with the vaccination status of a 5 % r and om sample ( N=2073 ) of the background cohort and analysed in a case-cohort design . BCG vaccination reduced the risk of lymphomas ( HR=0.49 ( 95 % CI : 0.26 - 0.93 ) ) , whereas smallpox vaccination did not ( HR=1.32 ( 0.56 - 3.08 ) ) . With the small number of leukaemia cases , the analysis of leukaemia had limited power ( BCG vaccination HR=0.81 ( 0.31 - 2.16 ) ; smallpox vaccination HR=1.32 ( 0.49 - 3.53 ) ) . The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas In 1950 approximately one-half of the population of Muscogee County , Georgia , and Russell County , Alabama , who were over the age of 5 years took part in a tuberculosis survey that included a controlled trial of BCG vaccination .  A total of 16,913 persons were classed as vaccinees and 17,854 as controls .  By the end of 1977 , nearly 28 years later , 423 controls and 429 vaccinees were known to have developed cancer . Inasmuch as only 379 cancer cases were expected among vaccinees , there was no indication of any general protective effect of BCG vaccination against cancer . There were 18 sites with 5 or more cancers among controls and vaccinees and with observed/expected ratios greater than 1.49 or less than 0.68 . Fewer cancers among vaccinees than expected were found for only 6 of these 18 sites . Among the sites with excessive cases among vaccinees was the lymphoma-Hodgkin 's disease-leukemia group [ International Classification of Diseases ( Eighth Revision ) codes 200 - 202 , 204 - 207 ] , a group suspected from previous studies of occurring more frequently after BCG vaccination Data obtained in animals indicate that neonatal immune responses are biased toward Th2 . This could reduce the efficacy of vaccines against viral and mycobacterial diseases . The ability of human newborns to develop a Th1 immune response upon immunization has not been studied . Since the vaccine Mycobacterium bovis bacillus Calmette-Guérin ( BCG ) triggers a Th1-type response in adults , we investigated whether it induces a similar response in newborns and whether age at vaccination influences immunogenicity . We found that BCG vaccination at birth induces a memory Th1-type response of similar magnitude to that when given later in life . This study demonstrates that human newborns can be immunized against pathogens controlled by a Th1 immune response
Lymphoma etiology remains ill-defined , but immune factors seem to play a major role .
The Bacillus Calmette-Guérin ( BCG ) vaccine , a non-specific stimulator of the cellular immune response , could influence lymphoma risk .
Previous studies addressing this issue showed conflicting results .
In this study , we performed a systematic review and meta- analysis to synthesize the epidemiological evidence .