The limitations of using hospital controls in cancer etiology--one more example for Berkson's bias

The aim of this report was to present an example in which Berkson's bias, most probably, affected the results of a study by overriding the influence of a well-established risk factor (smoking) in the etiology of bladder cancer. The results of a study of 140 male patients with bladder cancer and 280 matched hospital controls confirmed the etiological role of industrial occupation in bladder cancer but failed to confirm the role of smoking. We reanalyzed the proportion of chronic related morbidity as well as the rate of smoking in patients with lung disease in cases and controls. A similar distribution of some chronic diseases known to be highly associated with smoking was found among cases and controls. Highest smoking rates (91%) were found among patients with bladder cancer who also reported a concomitant lung disease, and the lowest rate (67%) was noted among controls without lung disease (p = 0.009). Using the prevalence of smoking in the general Israeli male population (50%), significant odds ratio for bladder cancer among ever smokers compared to never smokers was observed. Our conclusion is that a possibility of Berkson's bias should be considered whenever hospital controls are used. Information on diseases related to the risk factor under consideration and on the prevalence of the risk factor in the general population, may demonstrate the existence of such a bias.