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 : 1.73.3). 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% Cl : 4.3-45.0) or deaths from cardiovascular diseases (monozygotic pairs: RR = 3.9; 95% CI : 1.9-11.5; 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.