Cigarette smoking and risk of large cell carcinoma of the lung: a case-control study in Uruguay
Introduction
Undifferentiated large cell carcinoma is the fourth cell type in frequency among histologic varieties of lung cancer [1]. It is also the less studied of all types of lung cancer. Most previous studies [2], [3], [4], [5], [6], [7] show only the estimates of large cell cancer for ever or current smokers, with the intensity or duration of this tumor being mostly unknown. In particular, the study by Morabia and Wynder [7] suggested that large cell pulmonary cancer was not related with tobacco smoking. These results prompted this group of epidemiologists to conduct a larger study on large cell lung cancer and its relationships with tobacco smoking [8]. To our knowledge, this new study is the only one which deals exclusively with large cell lung cancer. In this retrospective study, detailed estimates for most smoking indices are shown [8]. Nevertheless, the study by Muscat et al. [8] presented some shortcomings. In the first place, approximately 50% of the control series comprised cancer controls. Among cancer controls the following sites were included: colon, rectum, prostate, skin, lymphoma, leukemia, breast and ovary. Some of these cancer sites have been suggested as related with tobacco smoking [9], [10], [11], [12]. This could have resulted in an underestimation of the relative risks. Secondly, the study by Muscat et al. [8] was conducted in the United States, a country in which smoking of air-cured (black) tobacco is most unusual. Therefore, we decided to examine in detail cigarette smoking variables in relation with large cell carcinoma of the lung, in the setting of a hospital-based case-control study conducted in Montevideo, Uruguay. This study excludes cancer controls and allows the estimation of OR’s associated with black tobacco and blond tobacco.
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Material and methods
In the time period 1988–2000, as part of an on-going study on lung cancer, we identified 154 newly-diagnosed cases of patients with large cell lung cancer. All these cases had been microscopically diagnosed by expert pathologists and subsequently validated by two of the authors (HDP, EDS). From this initial number, five men presented advanced disease with brain metastases, leading to a final total of 149 cases (139 men and 10 women) (response rate 96.7%).
In the same time period and in the same
Results
As a result of the matched design, age sex, residence, and urban/rural status were very similar among cases and controls (Table 1). Cases were significantly less educated than controls (P<0.001).
Odds ratios of large cell carcinoma for tobacco variables among men and both sexes combined are shown in Table 2. The results are presented only for men and both sexes combined, since the low number of women precluded the calculation of most of ORs. Also, the estimates for men are unstable since there
Discussion
According to the results of our study, undifferentiated large cell carcinoma of the lung is strongly associated with tobacco smoking. In fact only four cases (2.7%) of the case series were non smokers. This finding replicates the findings of the study by Travis [16], according to which almost 100% of large cell neuroendocrine carcinomas of the lung, like small cell pulmonary cancers, were smokers. Moreover, one in a total of 139 male cases was a never smoker (0.7%), whereas three women in 10
Acknowledgements
This study was supported by a grant from International Agency for Research on Cancer, Lyon, France (ECE/98/17).
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