Investigation of the relationship between smoking and appendicitis in Australian twins CHRIS OLDMEADOW, IAN WOOD, KERRIE MENGERSEN, PETER M. VISSCHER, NICHOLAS G. MARTIN, AND DAVID L. DUFFY PURPOSE: Appendicitis is an inflammation of the appendix, the etiology of which is still poorly under- stood. Previous studies have shown an increased risk for cigarette smokers but no accounts for the timing of exposure to smoking relative to appendectomy were made. METHODS: Based on questionnaire data, both cohort and co-twin case-control analyses were conducted to assess the effect of active cigarette smoking on appendectomy in 3808 Australian twin pairs. Smoking status was defined as a time-dependent covariate to account for differences in timing of smoking initiation and onset of appendicitis. RESULTS: The questionnaire had a 65% pairwise response rate. After controlling for sex, age, and year of birth, appendectomy risk in current smokers was statistically significantly increased by 65% relative to never-smokers. This was largely unchanged by the duration or intensity of smoking and was not affected by socioeconomic status or father’s occupation. The effect was stronger in females. Among former smokers, increased time since quitting significantly reduced the odds ratio of appendectomy by 15% for every year since quitting. CONCLUSION: After adjustment for age and other confounders, there was an increase in risk of appen- dectomy among current smokers relative to never-smokers, particularly in females. This study adds to the body of knowledge on the effects of tobacco smoking on the gastrointestinal tract. Ann Epidemiol 2008;18:631–636. Ó 2008 Elsevier Inc. All rights reserved. INTRODUCTION Smoking has been variously associated with diseases of the gastrointestinal tract: increased risk of Crohn’s disease (1) and peptic ulcer disease (2), as well as a decreased risk of ul- cerative colitis (UC) (3). However, it has also been reported that appendectomy is protective against UC (4) and that this reduced risk is specific to appendectomies in persons younger than 20 years of age (5, 6), in particular when these are due to appendicitis (6). Since both smoking and appen- dectomy appear to be protective against UC, dependencies between the two factors might indicate that this protective effect is partly due to confounding. An increased risk of appendectomy among active smokers and children of parents who smoke was reported by Montgomery, Pounder, and Wakefield (7). Although no claims of causation were made, it was suggested that smoking might disable an immune response associated with UC and leave the appendix vulnerable to inflamma- tion. The study has been criticized for failing to account for the timing of exposure to smoking relative to appendec- tomy (8). Butland and Strachan (9) found further evidence for the association between passive smoking and appendec- tomy in children younger than 16 years of age. The aim of this paper is to investigate the association be- tween reported personal tobacco smoking and appendec- tomy in a large Australian twin cohort. Two statistical approaches were employed. The first was a cohort analysis using a time-dependent smoking status variable. The second was a co-twin case-control analysis in which the twin struc- ture of the data afforded an assessment of whether depen- dencies between smoking and appendectomy are due to unique environment or common genetic influences. METHODS Sample The Australian NHMRC Twin Registry (ATR) is a volun- teer twin registry established in 1979. The data used in the present study are derived from a questionnaire mailed to 5,967 ATR twin pairs on November 14, 1980 and returned over a period of 2 years to 1,982 (10). Both members of 3,808 pairs completed and returned the questionnaire. From the Department of Mathematical Sciences, Queensland University of Technology (C.O., I.W., K.M.) and the Genetic Epidemiology Unit, Queensland Institute of Medical Research (P.M.V., N.G.M., D.L.D.). Address correspondence to: Chris Oldmeadow, Queensland University of Technology, Mathematical Sciences, O Block, Gardens Point Campus, Brisbane, Australia. Tel.: 07 3138 1292. E-mail: c.oldmeadow@ student.qut.edu.au. Received January 9, 2008; accepted April 6, 2008. Ó 2008 Elsevier Inc. All rights reserved. 1047-2797/08/$–see front matter 360 Park Avenue South, New York, NY 10010 doi:10.1016/j.annepidem.2008.04.004