A case-control study of smoking and gallbladder disease: importance of examining time relations

We report a case-control study of gallbladder disease and cigarette smoking. Subjects were 252 incident cases and 233 age-sex-residence-matched community controls. Three quarters of the subjects were women. The age-matched risk of gallbladder disease was increased in current smokers vs never-smokers [odds ratio (OR) = 1.6 and 1.3 in women and men, respectively] and in past smokers (OR = 1.5 for each sex). In light of earlier research, showing that, in women, certain risk factors for gallbladder disease may act maximally soon after first exposure, we examined time relations. In women, multivariable analysis showed that the risk increase was especially high in current-smoking women less than 35 years of age [OR = 3.5, 95% confidence interval (CI) = 1.2-9.8] and in women who had been smoking for 1-8 years (OR = 2.8, 95% CI = 1.1-7.1). These results indicate that, in women, the smoking-related risk of gallbladder disease is greatest soon after first exposure--as has also been reported for oral contraceptive use. The findings highlight the potential for mis-estimating risk in case-control studies when late-occurring cases have a different relation to the exposure factor than do the early-occurring cases within the original, albeit undocumented, exposure cohort.