Breast cancer, passive and active cigarette smoking and N-acetyltransferase 2 genotype

Abstract

The relationship of breast cancer to cigarette smoking is inconsistent in the literature, possibly due in part to heterogeneity in carcinogen metabolism. 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 collected prior to biopsy diagnosis to blind subjects and interviewers. Histopathology showed 113 cases with mammary carcinoma (30 carcinoma in situ) and 278 controls with benign breast disease. NAT2 genotype was determined using allele-specific polymerase chain reaction amplification to detect slow acetylator mutations. Effects of passive and active tobacco smoke and of NAT2 genotype on breast cancer risk were examined with logistic regression controlling for known risk factors. Models first included all controls, and subsequently 107 with no or low risk (normal breast or no hyperplasia), and finally 148 with high risk (hyperplasia, atypical hyperplasia, complex fibroadenomas). Referents had no active or passive smoke exposure. We found no association between breast cancer risk and NAT2, smoking status (never, former, current), smoking duration, or cigarettes per day. There were no effects of passive exposure among never-smokers. Models were unchanged across control groups. There were no statistical interactions between tobacco smoke exposure and NAT2. The results were similar when restricting the analysis to invasive 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.

Cigarette smoking and breast cancer risk: A long latency period?

“…Population‐based studies avoid some of these limitations, but the potential for recall and selection bias must still be considered. Although the results of 7 hospital‐based26, 27, 28, 29, 30, 31, 32 and 4 screening‐based31, 33, 34, 35 studies are mixed, they generally are not inconsistent with our own findings. Only one of these studies examined smoking of 40 cigarettes/day or more28 and found a 30% increased risk among high‐intensity smokers compared to never‐smokers.…”

Passive Smoking and Risk of Breast Cancer in the California Teachers Study

“…Few studies have evaluated the effect of NAT2 variants in studies of passive smoking and breast cancer. Two case control studies have suggested no modification of observed main effects for rapid vs. slow acetylators (29, 45), but a German case-control study suggested that, contrary to the observed relationship with active smoking in which slow acetylation is associated with greater risk, passive smoking was associated with higher risk in rapid acetylators (46). Although there have been some interesting, if null, studies of passive smoking and other polymorphisms (35, 47, 48) this remains a relatively uncharted area of inquiry.…”

Genetic variation in N-acetyltransferases 1 and 2, cigarette smoking, and risk of non-Hodgkin lymphoma

“…Previous studies have suggested that women with the slow acetylation phenotypes for NAT2 may be more adversely affected by tobacco smoking (39–41) but the data have been inconsistent (42–43). Our results indicate that the NAT1 rapid genotype (without NAT*10 alleles) increases the risk of NHL in smokers relative to the risk observed in non-smokers, indicating that NAT2 activation (via O-acetylation) is more important than deactivation.…”