Differential effect of NAT2 on the association between active and passive smoke exposure and breast cancer risk.
BACKGROUND
Polymorphisms in the N-acetyltransferase 2 (NAT2) gene influence the rate of metabolism of aromatic and heterocyclic amines present in tobacco smoke. Because the physicochemical composition of mainstream and sidestream smoke differ, we conducted a case-control study to assess a possible differential effect of NAT2 genotype on the relationship between active/passive smoke exposure and breast cancer risk.


METHODS
Breast cancer patients diagnosed by 50 years of age and population-sampled controls were interviewed to obtain detailed lifetime active and passive smoking history. NAT2 genotype was determined in 422 breast cancer patients and 887 controls. Multivariate logistic regression analysis was performed to estimate breast cancer risk in relation to smoking history by acetylator status and interaction effects.


RESULTS
Compared with women never regularly exposed to tobacco smoke, odds ratios (ORs) for current smoking and ex-smoking were 1.7 [95% confidence interval (CI): 1.0-2.9] and 1.2 (95% CI, 0.7-2.0) in slow acetylators, and not increased in rapid acetylators. Active smoking variables, such as pack-years, duration of smoking, and time since cessation, showed significant dose-response relationships with breast cancer risk among slow acetylators but not rapid acetylators. In contrast, passive smoking was associated with higher risk in rapid than in slow acetylators, with ORs of 2.0 (95% CI, 1.0-4.1) and 1.2 (95% CI, 0.7-2.0), respectively.


CONCLUSIONS
Our results suggest that the NAT2 status has a differential effect on the association of active and passive smoking with breast cancer and demonstrate the need to consider possible different mechanisms associated with exposure to main- and sidestream tobacco smoke.
Chang-Claude
Jenny
J
Division of Clinical Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany. j.chang-claude@dkfz.de
Kropp
Silke
S
Jäger
Birgit
B
Bartsch
Helmut
H
Risch
Angela
A
D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D016540:Smoking Cessation; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D014028:Tobacco Smoke Pollution; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human