title: Permanent hair dyes and bladder cancer: risk modification by cytochrome P4501A2 and N-acetyltransferases 1 and 2.
abstract: We have previously reported permanent hair dye use to be a significant risk factor for bladder cancer in US women. We also have examined N-acetyltransferase-2 (NAT2) phenotype in relation to the hair dye-bladder cancer relationship, and found that the association is principally confined to NAT2 slow acetylators. In the present study, we assessed the possible modifying effects of a series of potential arylamine-metabolizing genotypes/phenotypes (GSTM1, GSTT1, GSTP1, NAT1, NAT2, CYP1A2) on the permanent hair dye-bladder cancer association, among female participants (159 cases, 164 controls) of the Los Angeles Bladder Cancer Study. Among NAT2 slow acetylators, exclusive permanent hair dye use was associated with a 2.9-fold increased risk of bladder cancer (95% CI = 1.2-7.5). The corresponding relative risk in NAT2 rapid acetylators was 1.3 (95% CI = 0.6-2.8). Frequency- and duration-related dose-response relationships confined to NAT2 slow acetylators were all positive and statistically significant. No such associations were noted among NAT2 rapid acetylators. Among CYP1A2 'slow' individuals, exclusive permanent hair dye use was associated with a 2.5-fold increased risk of bladder cancer (95% CI = 1.04-6.1). The corresponding risk in CYP1A2 'rapid' individuals was 1.3 (95% CI = 0.6-2.7). Frequency- and duration-related dose-response relationships confined to CYP1A2 'slow' individuals were all positive and statistically significant. No such associations were noted among CYP1A2 'rapid' individuals. Among lifelong non-smoking women, individuals exhibiting the non-NAT1*10 genotype showed a statistically significant increase in bladder cancer risk associated with exclusive permanent hair dye use (OR = 6.8, 95% CI = 1.7-27.4). The comparable OR in individuals with the NAT1*10 genotype was 1.0 (95%CI = 0.2-4.3). Similarly, all frequency- and duration-related dose-response relationships confined to individuals possessing the non-NAT1*10 genotype were positive and statistically significant. On the other hand, individuals of NAT1*10 genotype exhibited no such associations.
authors.affiliation: USC/Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033-0800, USA. mgago@hsc.usc.edu
authors.forename: Manuela
authors.initials: M
authors.lastname: Gago-Dominguez
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bell
authors.forename: Mary A
authors.initials: MA
authors.lastname: Watson
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yuan
authors.forename: J Esteban
authors.initials: JE
authors.lastname: Castelao
authors.forename: David W
authors.initials: DW
authors.lastname: Hein
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Chan
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Coetzee
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Ross
authors.forename: Mimi C
authors.initials: MC
authors.lastname: Yu
mesh_terms: D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006202:Hair Dyes / Q000009:adverse effects*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000209:etiology*
chemical_list: D006202:Hair Dyes; D007527:Isoenzymes; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human