Infection, inflammation and cancerписьмо
Аннотация: In their recent excellent paper on the unifying roles for regulatory T-cells and inflammation in cancer,1 Erdmann et al. remark that, in contrast to autoimmune diseases, there have been few studies on the hygiene hypothesis in relation to cancer. This is undoubtedly true, but there are some important and illustrative examples that point to possible preventive strategies based on currently available vaccines. These examples relate principally to leukaemia and melanoma, and there is evidence that the risk of both diseases is reduced by vaccination early in life with bacille Calmette–Guérin (BCG). In the case of leukaemia it has been shown in several studies, recently summarised in a meta-analysis,2 that the same hygiene-related factors that, by reducing or delaying exposure to infectious agents, reduce protection of children against allergic disorders also reduce protection against acute leukaemia. Several studies before 1990 showed that neonatal BCG vaccination significantly reduces the risk of leukaemia and other cancers in childhood and early adult life, up to 74% risk reduction, although other studies showed only a small level of protection.3 The protective effect of BCG against tuberculosis varies greatly, depending on where and at what age it is given. Therefore, when various studies on leukaemia were compared, it was evident that high levels of protection were restricted to regions where the vaccine was administered early in life and where it afforded high levels of protection against tuberculosis.3 The risk of melanoma is rising in many industrialised countries at a higher rate than for any other cancer except lung cancer in women, suggesting that hygiene-related factors might likewise be involved. Accordingly, a multicentre study was conducted in several European countries and Israel to determine the impact on the history of infectious diseases on the risk of melanoma, and revealed that a history of certain infections with fever >38.5°C, including pneumonia, sepsis, pulmonary tuberculosis and Staphylococcus aureus infection, were associated with trend towards protection against this disease; although because of low numbers, this was not statistically significant (odds ratio of risk 0.37, 95% confidence interval 0.10–1.42).4 However, when the impact of vaccination strategies on the risk of melanoma was investigated in the same study, a much clearer picture emerged. Thus, vaccination with either BCG or vaccinia, or both, early in life conferred protection, with overall adjusted odds ratios of risk (95% confidence intervals in parentheses) being 0.40 (0.18–0.85) for BCG alone, 0.60 (0.36–0.99) for vaccinia alone and 0.41 (0.25–0.67) for both vaccines. It was also, somewhat surprisingly, found that the prognosis of patients with inoperable melanoma was significantly better in those who had received one or both vaccinations in early childhood.5 There was also a trend to protection in those who had a history of the serious infections mentioned above but the numbers were too low to permit a meaningful statistical analysis. A hypothesis to explain the association of the natural infections and the vaccinations with protection against melanoma was based on the expression on the cell membrane of most melanomas of an epitope (HERV-K-MEL) coded by an endogenous retrovirus in the HERV-K family, which served as a potential target for cytolytic T-cells.6 Homologous amino acid sequences were found in the protective infectious agents and vaccines but not in those what did not afford protection. It was postulated that these agents afforded protection by generating cross-reacting cytolytic immune responses. This hypothesis predicted that other vaccines expressing homologous epitopes would likewise confer protection. Such an epitope is expressed by the 17D yellow fever vaccine and, despite methodological problems, the prediction of a protective effect was confirmed.7 It was also found that there was a delay in expression of protection of around 10 years, suggesting that the protective effect was maximal at a very early stage of the development of the melanoma. It is not clear whether a similar immune mechanism protects against leukaemia. Although there is evidence that HERV-K is expressed in leukaemia cells,8 the occurrence of the HERV-derived epitope expressed in many melanomas has not been reported in this condition. However, it is possible that other HERV-derived epitopes also cross-react with one or more of the numerous epitopes of BCG. Whatever is the mechanism, the evidence presented suggests that currently available vaccines could give useful levels of protection against two increasingly common cancers of young people. An additional hygiene-related factor relevant to cancer risk is occupational exposure to animals. Thus, in Italy, farmers working with cattle were significantly less likely to develop certain cancers than were crop or fruit farmers.9 The level of protection was directly proportional to the number of cattle that farmers was exposed to and waned if they left cattle farming for another profession. Protection was most evident in the case of lung cancer as this was the most prevalent cancer, but significant protection was seen with bladder, pancreas and oesophagus, with a trend to protection with several others. Although the exact microbiological factors involved in protection were not determined, inhalation of endotoxins or other bacterial components is a distinct possibility. These observations were confirmed in a very similar study in Finland,10 and a recent meta-analysis,10 where the summary risk of lung cancer was 0.62 (0.52–0.75) for agricultural workers. The relative risk of lung cancer was below 1.0 for most subgroups defined according to sex, study design, outcome, smoking adjustment and geographic area. These high-quality studies add weight to the hypothesis that occupational exposure to endotoxin in agriculture is protective against lung cancer and could thus pave the way to further preventive strategies. John M. Grange*, Bernd Krone , Giuseppe Mastrangelo , * Centre for Infectious Diseases and International Health, University College London, London, United Kingdom, Centre for Hygiene and Human Genetics, University of Göttingen, Göttingen, Germany, Department of Environmental Medicine and Public Health, University of Padua, Padua, Italy.
Год издания: 2010
Авторы: John M. Grange, Bernd Krone, Giuseppe Mastrangelo
Издательство: Wiley
Источник: International Journal of Cancer
Ключевые слова: Immune responses and vaccinations, Epigenetics and DNA Methylation, Immune cells in cancer
Другие ссылки: International Journal of Cancer (HTML)
PubMed (HTML)
PubMed (HTML)
Открытый доступ: closed
Том: 128
Выпуск: 9
Страницы: 2240–2241