In this case–control study, personal hair dye use was not associated with bladder cancer risk. This finding did not clearly differ by type of hair dye, duration, or frequency of use, dye color, or extent of use.
Our findings are consistent with most previous epidemiological studies [14
] that have generally reported no association between hair dye use and bladder cancer risk. Similarly, a few meta-analyses have been conducted [28
]. The interpretation of findings from the meta-analysis by Hunchareck and Kupelnick [30
] differs from that of Takkouche et al. [29
]. Although both papers evaluated nearly the same set of studies, Hunchareck and Kupelnick [30
] suggest an increased bladder cancer risk exists, while Takkouche et al. [29
] concludes that there is no association. In the meta-analysis by Hunchareck and Kupelnick sensitivity analyses to examine the influence of hair dye types, color, and study design found the risk of developing bladder cancer increased by 22–50 % among those using permanent hair dye products versus those who do not. The most recent meta-analysis by Kelsh et al. [28
] reported associations in individual studies ranging from 0.8 to 1.5, with a meta-relative risk of 1.01 (95 % CI, 0.89–1.14). Thus, the overall results are not yet converging.
In contrast with nearly all other studies, the study of Gago-Dominguez et al. [22
] suggested an increased bladder cancer risk of permanent hair dye use (OR, 1.5; 95 % CI, 0.97–2.3), which was more pronounced among females having used hair dyes more than 12 times per year for more than 15 years (OR, 3.3; 95 % CI, 1.3–8.4). Although no overall association between hair dyes and bladder cancer was found in a recently published study from New England, increased risks were observed in certain subgroups [24
]. The New England study found that women who used permanent dyes and had at least a college degree had an increased risk of bladder cancer (OR, 3.3; 95 % CI, 1.2–8.9). Our study, however, showed no evidence that the lack of association between hair dyes and bladder cancer risk was modified by educational level. On the other hand, our risk estimates are not robust because of the small number of female cases exposed to hair dyes in some subgroups, resulting in limited statistical power. Also, the New England study found, similar to the California study [31
], that the risk was more pronounced among exclusive users of permanent hair dyes who had the NAT2 slow acetylation phenotype (OR, 7.3; 95 % CI, 1.6–32.6). By contrast, a previous study from Spain, the Spanish Bladder Cancer Study, failed to confirm an increased risk of bladder cancer in a population of personal hair dye users and found no increased risk in NAT2 slow acetylators [16
]. As data on specific genetic polymorphisms involved in the metabolism of aromatic amines was not available in the current study, we were not able to examine the influence of genetic susceptibility on the risk of bladder cancer associated with hair dye use.
In the present study, we found no gradient in risk with longer duration of hair dye use (i.e., more than 10 years). A consideration with respect to the interpretation of the previous studies is that the numerous chemicals used in hair dyes have varied over time. After the 1980s, several aromatic amines (e.g., 2,4-diaminotoluene, 2,4-diaminoanisole and 4-ABP) were banned as hair dye ingredients after they were found to be carcinogenic in rodents [32
]. It is therefore important to examine the time period of dye use because hair dye formulations that occurred around 1980s may be more carcinogenic than newer dyes formulated in response to concern about potential cancer risk. Although we collected detailed information on duration of hair dye use, we have no information about year at first dye use. On the other hand, the presence of the most common permanent hair dye ingredient, p
-phenylenediamine has remained unchanged for the last 50 years even though animal data support its carcinogenicity [33
]. Also, a few new ingredients were introduced during the last 20 years [3
]. Bladder cancer has very long latency times, so that effects of historical exposure to aromatic amines in hair dyes may still be observed decades later.
This study may suffer from several limitations inherent to case–control study designs. Information on hair dye use was assessed after the diagnosis of bladder cancer and is therefore sensitive to recall bias. Due to the media attention for this topic, it is possible that cases reported personal hair dye use differently from controls, although it is more likely that this would have resulted in inflated odds ratios. Another limitation of the study is the relatively low response rate among controls, possibly leading to selection bias. A short telephone questionnaire was completed by 100 non-respondent controls to evaluate whether they differed from the participating controls. Compared to non-respondents, respondents were somewhat more highly educated and were more likely to have a paid job (data not shown). Because users of hair dyes among the controls are somewhat higher educated (Table ), it is possible that we overestimated hair dye use in the general female population that may explain part or all of the observed odds ratios. On the other hand, additional adjustment for educational level did not change the results.
One of the strengths of this study is the information collected about various types of hair dyes (i.e., permanent and temporary dyes). Hair dyes differ in level of suspected carcinogenic chemicals, that is, permanent hair dyes have a higher content of aromatic amines [32
]. Nevertheless, we found no substantial difference in risks between types of hair dye. Although we evaluated different types of hair dyes separately, the category of temporary dyes could also be further separated into water-soluble dyes that withstand only one shampooing (temporary dyes) and semi-permanent dyes that are usually synthetic and persist longer than temporary dyes (4–5 shampooings), because these types of products vary slightly in composition. Combining the temporary and semi-permanent dyes may have lead to inability to detect an increased risk for one or the other type. In addition, we stratified the analyses by hair dye color, because dye colors differ in chemical properties, that is, in general dark dyes contain higher concentrations of aromatic amines than lighter shades [32
]. A few studies [17
] did suggest an increased bladder cancer risk among long-term users of dark dyes. The low prevalence of exposure to dark hair dyes in most populations may explain the discrepancies in these results. We collected information on hair dye color, but were unable to present associations between black dye use and bladder cancer risk because none of the cases reported black hair dye use. We did not find any association for blond, brown, and red hair dye use. It is important to note, however, that these findings were also based on small numbers of cases.