[54], [55]. Recently, Le Marchand et al. [56] used urinary biomarkers to test whether rs1051730 and rs16969968 are associated with a higher level of nicotine and exposure to tobacco-specific carcinogenic substances per cigarette dose in a Hawaii study of 583 men and women of European, Japanese, or Native Hawaiian ancestry who were long-term smokers of more than 10 cigarettes per day. Although the T of rs1051730 and A of rs16969968 alleles were less common in Japanese Americans (3%) and Native Hawaiians (∼19%) than in European Americans (34%), those investigators found that carriers of T of rs1051730 or A of rs16969968 extract a greater amount of nicotine (P = 0.004 and 0.003, respectively) and those A carriers of the rs16969968 had a higher internal dose of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (P = 0.03) per cigarette than non-carriers. In another study with a sample size of ∼17,300 subjects from five LC studies and four upper aerodigestive tract cancer studies, Lips et al. [57] revealed no association between rs16966968 and SI or SC, age at SI, or age at SC. However, when cancer cases and controls were combined (after adjustment for case/control status), the adjusted mean difference between the two homozygote genotypes was 1.2 CPD
