Such are the conclusions of a broad prospective study, including almost 100,000 patients over a 30-year period and conducted under the auspices of WHO's prestigious International Agency for Research on Cancer of the World Health Organization, the no less renowned Karolinska Institute of Stockholm and the University of Uppsala.

The results are published in the January issue of the European Respiratory Journal (ERJ).

The idea of a link between asthma and future lung cancer had already been broached by previous epidemiological studies, some of which noted, interestingly, that only men were affected. (Other studies came to the conclusion that there was no such connection.)

Yet most of the studies were conducted retrospectively on subjects already suffering from bronchial cancer, who were asked to recall elements of their medical history that might provide evidence for a link between asthma and cancer.

This method proved doubly unsatisfactory, not only because the cancer was already diagnosed, but above all because patient ability to report previous diseases with complex symptoms such as asthma is too uncertain to represent a reliable scientific basis.

Contrary to this, the major study published in January's ERJ by Paolo Boffetta, Weimin Ye, Gunnar Boman and Olof Nyren has the double advantage of being prospective and covering a large group which was monitored for several decades. The authors used the renowned Swedish national health registers, which allowed them to monitor the medical history of over 90,000 subjects.

"Over a period of 30 years", explains Paolo Boffetta, of the Unit of Environmental Cancer Epidemiology of the International Agency for Research on Cancer in Lyon (France), "we sought to identify the subjects who had been hospitalized in Sweden and diagnosed with asthma. In order to increase the value of our study, we only included subjects who not only remained alive one year after their discharge from hospital, but, above all, presented no sign of cancer at that stage."

Of the 118,000 patients originally identified, only 92,986 were eventually included in the study. Their health was monitored from the second year after the asthma diagnosis until the last day of the period covered by the study.

Taking into account the steady influx of new patients and mortality, subjects were, on average, monitored for eight and a half years. This represents a total of almost 700,000 monitored person-years.

The researchers' first conclusion was that asthmatics are affected by lung cancer more frequently than the general population: the 713 cancers registered over the course of the study exceeded the anticipated level by 58%.

They also reached the conclusion that the situation is even worse for women, whose excess risk is 78%, against 51% for men.

It appears now to be established that asthmatics are at increased risk of lung cancer. However, the reason for the connection remains to be seen, and the authors are cautious.

"We do not really know if asthma as such causes the increased risk," notes Boffetta. "There could be one mechanism causing both asthma and cancer, for example chronic inflammation leading to an excess of free radicals."

It is known that bronchiolar inflammation, through the activation of neutrophils and phagocytes, generates free radicals, and there is evidence that the antioxidant levels in the respiratory tract lining of asthmatics are reduced.

Since free radicals have the potential to cause genetic damage, local abundance may contribute to malignant transformation.

"Yet there could quite possibly be a susceptibility factor common to asthma and cancer," adds Boffetta, "or that an external factor is involved and plays a role both in the activation or progression of asthma and the contracting of lung cancer. Such a role could be played, for example, by environmental factors, above all, tobacco smoking".

Support for this last hypothesis could be drawn from the fact that, on examining the various types of cancer for which excessive risk was found in asthmatics, the research team found increased levels of histological types commonly found in smokers (such as squamous-cell carcinomas), which were no less frequent in female asthmatics than in their male counterparts.

The article states in conclusion that this study confirms the link between asthma and subsequent bronchial cancer. Contrary to previous retrospective or small-scale studies, it clearly demonstrates that women do not enjoy any reduced risk; on the contrary, their risk might even be higher.

"The prospective monitoring of young patients with known smoking habits over a longer period could provide useful information on the timing of a possible carcinogenic effect of asthma," according to Boffetta.


[Contact: Paolo Boffetta]

03-Jan-2002