Twenty-Four Year Mortality in World War II US Male Veteran Twins Discordant for Cigarette Smoking

BACKGROUND: This study was undertaken to test the constitutional hypothesis which attributes the association of tobacco smoking with morbidity and mortality to genetic predispositions to smoking and/or disease. METHODS: Subjects were World War II veterans, born in the US between 1917 and 1927, and surveyed at mean age 47 for present and past smoking habits. Twenty-four year mortality follow-up data were available for 1515 male twin pairs discordant for lifelong cigarette smoking. Using the first or only death of a smoking-discordant pair, 24-year relative risks of mortality were calculated by zygosity, cause of death, amount smoked, and age at death. RESULTS: We found that active smokers at baseline, regardless of zygosity, had a higher risk of death than their co-twins who had never smoked or quit smoking (monozygotic pairs: relative risk [RR] = 2.5; 95% confidence interval [CI] : 1.3-6.1 and RR = 1.7; 95% CI : 1.2-2.5; dizygotic pairs: RR = 2.4; 95% CI : 1.4-3.8 and RR = 2.0; 95% CI : 1.7-3.3). The elevated risk of death among smokers was due to deaths from lung cancer (monozygotic pairs: RR = 5.0; 95% CI: 2. 6-15.0; dizygotic pairs: RR = 11.0; 95% CI : 4.3-45.0) or deaths from cardiovascular diseases (monozygotic pairs: RR = 3.9; 95% CI : 1.9-115; dizygotic pairs: RR = 2.8; 95% CI : 1.7-4.9). Apart from these findings the relationship of smoking with all-cause mortality was stronger for earlier/younger deaths and for heavy to moderate smoking. CONCLUSIONS: The present results, from the largest and longest-studied series of smoking-discordant twins negate the constitutional hypothesis that genetic or early shared familial influences underlie the significant association between tobacco smoking and premature mortality.