Breast cancer and active and passive smoking: The role of the N-acetyltransferase 2 genotype

The association of breast cancer with passive and active smoking was invest igated in slow and fast acetylators of aromatic amines in a Geneva, Switzer land, study in 1996-1997. A slow acetylator was homozygous for one, or hete rozygous for two, of three N-acetyltransferase 2 (NAT2) polymorphisms deter mined on buccal cell DNA from 177 breast cancer cases and 170 age-matched, population controls. The reference group consisted of women never regularly exposed to active or passive smoke. Among premenopausal women, the odds ra tios were homogeneous in slow and fast acetylators: 3.2 (95% confidence int erval (Cl): 1.2, 8.7) for passive smoking and 2.9 (95% Cl: 1.1, 7.5) for ac tive smoking. Among postmenopausal women, the odds ratios for fast acetylat ors were 11.6 (95% Cl: 2.2, 62.2) for passive and 8.2 (95% Cl: 1.4, 46.0) f or active smoking; the corresponding effects were also apparent but less st rong in slow acetylators. After the nonexposed and the passive smokers were grouped in a single reference category, active smoking was associated with postmenopausal breast cancer in slow acetylators (odds ratio (OR) = 2.5, 9 5% Cl: 1.0, 6.2) but not in fast acetylators (OR = 1.3, 95% Cl: 0.5, 3.3). Thus, the associations of both passive and active smoking with breast cance r appear stronger in fast than in slow NAT2 genotypes. Separating passive s mokers from the nonexposed impacts on the inference about a possible NAT2-s moking interaction.