Our data suggest that women with long-term tobacco smoke exposure and with the COMT-HH or COMT-HL genotype have a higher risk of breast cancer than women with (a) long-term tobacco smoke exposure and the COMT-LL genotype – perhaps because these women have higher circulating concentrations of 2-hydroxylated estradiol due to their low COMT activity, or (b) no tobacco smoke exposure and the COMT-HH or COMT-HL genotypes – perhaps because these women have lower circulating concentrations of 2-hydroxylated estradiol due to the absence of tobacco smoke exposure. This evidence concerns the gene COMT and breast carcinoma.