Evidence for an intensity-dependent interaction of NAT2 acetylation genotype and cigarette smoking in the Spanish Bladder Cancer Study.
BACKGROUND
The N-acetyltransferase 2 (NAT2) enzyme detoxifies aromatic amines, an important class of carcinogens in tobacco smoke. Slow acetylation phenotype individuals have reduced detoxification capacity compared with those with a rapid/intermediate phenotype. Analysis of the Spanish Bladder Cancer Study found an odds ratio (OR) for slow acetylators relative to rapid/intermediate acetylators of 0.9 in never-smokers and 1.6 in ever-smokers, a 1.8-fold enhancement in smokers. Evidence indicates that acetylation is an exposure-dependent process, and thus the magnitude of the interaction may also depend on exposure level.


METHODS
We extend a comprehensive three-parameter linear-exponential model for the excess odds ratio (EOR) for smoking to include effects of NAT2 status, and reanalyse smoking and NAT2 status for the bladder cancer data.


RESULTS
We show that variations in smoking risk with NAT2 status result from interactions with smoking intensity (cigarettes per day) and not total pack-years of exposure. In addition, the relative increase in smoking risk in NAT2 slo acetylators increases with smoking intensity.


CONCLUSIONS
Analyses reveal an enhanced effect for smoking intensity and bladder cancer in NAT2 slow acetylators which increases with intensity.
Lubin
Jay H
JH
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Rockville, MD 20852, USA. lubinj@mail.nih.gov
Kogevinas
Manolis
M
Silverman
Debra
D
Malats
Núria
N
Garcia-Closas
Montserrat
M
Tardón
Adonina
A
Hein
David W
DW
Garcia-Closas
Reina
R
Serra
Consol
C
Dosemeci
Mustafa
M
Carrato
Alfredo
A
Rothman
Nathaniel
N
D000107:Acetylation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D010641:Phenotype; D018570:Risk Assessment / Q000379:methods; D012907:Smoking / Q000453:epidemiology* / Q000378:metabolism; D013030:Spain / Q000453:epidemiology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics; D014026:Nicotiana
D014028:Tobacco Smoke Pollution; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human