The relationship of breast cancer to cigarette smoking is inconsistent in t
he literature, possibly due in part to heterogeneity in carcinogen metaboli
sm. N-acetyltransferase 2 (NAT2) enzyme activity is believed to play a role
in the activation of tobacco smoke carcinogens. We examined the effect of
NAT2 genetic polymorphisms on risk of breast cancer from active and passive
smoking, Women were recruited from those who had suspicious breast masses
detected clinically and/or mammographically. Questionnaire data were collec
ted prior to biopsy diagnosis to blind subjects and interviewers. Histopath
ology showed 113 cases with mammary carcinoma (30 carcinoma in situ) and 27
8 controls with benign breast disease. NAT2 genotype was determined using a
llele-specific polymerase chain reaction amplification to detect slow acety
lator mutations. Effects of passive and active tobacco smoke and of NAT2: g
enotype on breast cancer risk were examined with logistic regression contro
lling for known risk factors. Models first included all controls, and subse
quently 107 with no or low risk (normal breast or no hyperplasia), and fina
lly 148 with high risk (hyperplasia, atypical hyperplasia, complex fibroade
nomas). Referents had no active or passive smoke exposure. We found no asso
ciation between breast cancer risk and NAT2, smoking status (never, former,
current), smoking duration, or cigarettes per day. There were no effects o
f passive exposure among never-smokers, Models were unchanged across contro
l groups. There were no statistical interactions between tobacco smoke expo
sure and NAT2. The results were similar when restricting the analysis to in
vasive cancers. These findings do not support the hypothesis that NAT2: is
a risk factor for breast cancer or that it alters susceptibility to tobacco
smoke, Pharmacogenetics 10:461-469 (C) 2000 Lippincott Williams & Wilkins.