Smoking (active and passive), N-acetyltransferase 2, and risk of breast cancer.
BACKGROUND
The relationship between smoking and breast cancer remains controversial. The study aim was to assess the relationship of passive and active smoking to breast cancer risk by N-acetyltransferase 2 (NAT2) phenotype, using a comprehensive assessment of both passive and active smoking.


METHODS
We undertook a population-based case-control study in Northeastern Ontario, Canada of 347 women diagnosed (2002-2004) with breast cancer and 775 population-based controls. The mailed study package included a questionnaire requesting information about established breast cancer risk factors, passive and active smoking, and a buccal swab for genetic analyses.


RESULTS
Among never-active smokers, a long duration of passive smoking was associated with an increased risk of breast cancer (odds ratio (OR) 1.86 (95% confidence interval (95% CI) 1.01-3.44) (test for trend (p=0.07)); that risk was more elevated for NAT2 slow acetylators (OR 2.76, 95% CI 1.16-6.59) (and highest in extremely slow acetylators), but not elevated for NAT2 fast acetylators (OR 1.17, 95% CI 0.42-3.23). Among active smokers more than 20 pack-years of smoking was associated with an OR of 1.34 (95% CI 0.92-1.96); more elevated among NAT2 fast acetylators OR 1.93 (95% CI 1.01-3.69) but not elevated among NAT2 slow acetylators. Women who were NAT2 fast acetylators in the highest quartile for duration of active smoking had an OR of 2.74 (95% CI 1.42-5.27), with a significant test of trend (p=0.005).


CONCLUSIONS
These findings suggest that passive and active smoking may be related to breast cancer, and the effect may be differentially modified by NAT2 phenotype. Further research into the genetic modification of a breast cancer-smoking relationship may help to reconcile earlier discrepant findings.
Conlon
Michael S C
MS
Epidemiology, Outcomes & Evaluation Research, Regional Cancer Program of the Sudbury Regional Hospital, Sudbury, Ontario, Canada P3E 5J1. mconlon@hrsrh.on.ca <mconlon@hrsrh.on.ca>
Johnson
Kenneth C
KC
Bewick
Mary A
MA
Lafrenie
Robert M
RM
Donner
Allan
A
D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D014028:Tobacco Smoke Pollution
D014028:Tobacco Smoke Pollution; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human