With regard to smoking adoption, two prospective studies have been conducted to date. However, the results of these studies are not consistent with respect to the risk of developing tobacco dependence in slower metabolizers. O’Loughlin and colleagues followed over 1,200 7th-grade students every 3–4 months for 4 years to study predictors of progression of smoking adoption (Karp et al., 2006; O’Loughlin et al., 2004). The incidence of conversion to tobacco dependence (had =3 of the criteria from the International Statistical Classification of Diseases [ICD] Version 10) was three times greater among the slower metabolizers (CYP2A6*2 or CYP2A6*4) (Karp et al., 2006), who also had a trend toward lower cigarette consumption, as compared to normal metabolizers (O’Loughlin et al., 2004). A recent study of smoking adoption among 222 adolescents followed from 9th to 12th grade reported that those with normal rates of metabolism (CYP2A6 *1/*1) progressed in degree of nicotine dependence (increase in Fagerstrom Test for Nicotine Dependence >1) more quickly than slow metabolizers (CYP2A6*9, CYP2A6*12, CYP2A6*2, or CYP2A6*4) (Audrain-McGovern et al., 2007). As seen in other adolescent and adult smokers,
