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Cancer Epidemiology Biomarkers & Prevention Vol. 15, 1746-1749, September 2006
© 2006 American Association for Cancer Research

Short Communication

Personal Permanent Hair Dye Use Is Not Associated with Bladder Cancer Risk: Evidence from a Case-Control Study

Jie Lin1, Colin P. Dinney2, H. Barton Grossman2 and Xifeng Wu1

Departments of 1 Epidemiology and 2 Urology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Xifeng Wu, Department of Epidemiology, Unit 1340, The University of Texas M.D. Anderson Cancer Center, 1155 Hermann Pressler Boulevard, Houston, TX 77030. Phone: 713-745-2485; Fax: 713-792-4657. E-mail: xwu{at}mdanderson.org


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Whether personal hair dye use is associated with an increased bladder cancer risk has been controversial and there are limited available data addressing this issue. We used a large case-control study of 712 incident bladder cancer cases and 712 age-, gender-, and ethnicity-matched controls to evaluate this association. After adjusting for confounding variables, the use of permanent hair dye was not associated with bladder cancer risk in all subjects [odds ratio (OR), 0.81; 95% confidence interval (95% CI), 0.50-1.30], in women (OR, 0.90; 95% CI, 0.41-1.96), or in men (OR, 0.68; 95% CI, 0.36-1.29). The lack of association was not modified by duration of use, frequency of use, lifetime use, age at first use, or color of use in subsequent stratified analyses. Our data do not support personal hair dye use as an important risk factor for bladder cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1746–9)


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Hair dyes are widely used in the United States, Europe, and East Asia. It is estimated that more than one third of women ages >18 years and >10% of men ages >40 years in the United States use some type of hair dye products, among which permanent hair dyes are the most widely used category and contribute to >80% market share in United States (1). The fact that almost any hair dye on the market contains small amounts of aromatic amines and that aromatic amines are carcinogenic in animals (2, 3) has generated great interest in studying the association between hair dye use and cancer risk, especially bladder cancer risk. Although occupational exposure to hair dyes by hairdressers and barbers has been shown to increase bladder cancer risk in a number of epidemiologic studies (4), whether or not personal hair dye use may increase bladder cancer risk remains controversial with fewer studies published and fewer cases and exposed individuals (4-6). In this study, we used one of the largest bladder cancer case-control studies to evaluate the association between personal hair dye use and bladder cancer risk.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Bladder cancer patients were recruited from The University of Texas M.D. Anderson Cancer Center and Baylor College of Medicine. Cases are enrolled from two ongoing studies: a bladder cancer case-control study and a case cohort study with the common goal of identifying genetic susceptibility to bladder carcinogenesis and clinical outcome. The case-control study started patient recruitment in 1999 and the case cohort study began in 2001. The procedures for subject recruitment and eligibility criteria were previously described (7). Briefly, cases are newly diagnosed and histologically confirmed urinary bladder cancer patients who had not received any previous chemotherapy or radiotherapy before enrollment. There were no recruitment restrictions on age, gender, ethnicity, or cancer stage. Cases enrolled in the case-control study are all Texas residents. Case recruitment is expanded to include all U.S. residents in the case cohort study. Among all cases recruited, the majority (~70%) is from Texas. We compared education level and total household income between residents of Texas and those from other states and found no significant differences. The controls are recruited in collaboration with the Kelsey-Seybold clinics, the largest private multispecialty physician group consisted of >23 clinics and >300 physicians in the Houston metropolitan area. The majority of controls visit the clinics for annual health check-ups. Controls are frequency matched to cases by age (±5 years), gender, and ethnicity. Controls have no prior history of cancer (except nonmelanoma skin cancer). For both cases and controls, after obtaining written informed consent, trained M.D. Anderson staff interviewers gave risk factor questionnaires to study participants. Data were collected on demographic characteristics (age, gender, ethnicity, etc.), work history, tobacco use history, and personal hair dye use. For personal hair dye use data, each participant answered questions about ever use of hair dye products, age when first started using hair dyes, frequency of use, type of hair dye used (permanent or semipermanent), and color of the most frequently used hair dye. Regular use of hair dye is defined as using hair dye products for 1 year or more.

Differences between cases and controls in the distributions of age, gender, ethnicity, smoking, and hair dye use were tested using the {chi}2 test, Student's t test, or Wilcoxon rank sum test when appropriate. Multivariate conditional logistic regression was done to calculate odds ratios (OR) while adjusting residual confounding effects of age and smoking status. All statistical tests were two sided with a type I error rate of 5%. Statistical analyses were done with the Stata software (version 8, College Station, TX).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The study included 712 bladder cancer cases and 712 healthy controls matched to cases by age, gender, and ethnicity. Gender and ethnicity were perfectly matched and there was no significant age difference between the cases (63.4 ± 11.2) and the controls (62.5 ± 10.9; P = 0.14). The cases had a significantly higher percentage of current (26.5%) and ever smokers (73.4%) than the controls (8.6% and 54.2%, respectively; P < 0.001). Among ever smokers, cases reported significantly higher levels of cigarettes consumption than controls (median pack-years, 37.5 versus 21.0; P < 0.001). The percentage of cases reporting ever use of hair dye was similar to that of the controls (26.5% versus 26.8%; P = 0.91). The use of different colors of hair dyes and the starting age of use were also similar in cases and controls (P = 0.75 and 0.12, respectively; data not shown).

Using subjects who had never used any hair dye products as the reference group, the ORs for regular use of permanent hair dyes and semipermanent hair dyes were 0.81 [95% confidence interval (95% CI), 0.50-1.30] and 0.82 (0.52-1.31), respectively (Table 1 ). The lack of association was seen in both women and men (Table 1). We then assessed the association between duration of use, frequency of use, lifetime use, age at first use, and bladder cancer risk (Table 2 ). The results were consistent in overall analysis and in either sex alone. However, due to the small sample size of male users, we only reported results for all subjects and for women only. In all variables, we chose cutoff points using quartiles and tertiles in controls, as well as cutoff points reported in the literature. As results were consistent regardless of the type of cutoff points chosen, we only reported tertile analysis and results based on literature cut off points. There were no significant associations overall and in women between bladder cancer risk and duration of use, frequency of use, lifetime use, and age at first use (Table 2). In addition, we also stratified the analysis by hair dye color because dark-colored dye contains higher concentration of dye loads than light-colored dyes (8). Again, no significant associations were found in any strata although the ORs tended to increase in users of black dyes (Table 2). Further, major formulation changes in hair dyes occurred around 1980, when many manufacturers replaced carcinogenic compounds in hair dye products (9); therefore, we did stratified analyses according to whether the subject started using hair dye products before or at 1980 or after 1980. No association was found in either stratum. The above analyses were also stratified by smoking status and there was no evidence of joint effects between hair dye use and smoking in bladder cancer risk (data not shown).


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  		Table 1. Regular hair dye use and bladder cancer risk

 

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  		Table 2. Personal hair dye use and bladder cancer risk in the study population and in women

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
There are a limited number of studies evaluating the association between personal hair use and bladder cancer risk and the results have been inconsistent. Two recent meta-analyses yielded contradictory conclusions, one found a pooled relative risk of 1.01 (95% CI, 0.89-1.14; ref. 5) and the other concluded that there was a 22% to 50% increased bladder cancer risk for permanent hair dye users (6). However, the latter report did not include the most recent negative case-control study (10) and the pooled significant ORs were obtained by excluding selected studies that the authors deemed questionable in study design. The largest cohort study with ~600,000 women (including 336 bladder cancer deaths) produced a RR of 1.08 (95% CI, 0.84-1.38) between permanent hair dye use and bladder cancer mortality after 16 years of follow-up (11). The caveat is that this report used cancer mortality as the end point, which would leave out the predominant bladder cancer subtype—superficial bladder cancer. It is known that superficial and invasive bladder cancer have different etiology (12). The largest multicenter case-control study (2,249 male cases, 733 female cases, and 5,792 controls) reported no significant association between hair dye use and bladder cancer risk (OR, 0.9; 95% CI, 0.8-1.1 for women; OR, 1.1; 95% CI, 0.8-1.4 for men; ref. 8). The lone positive study with 897 cases and matched controls found women who used permanent hair dyes at least once a month exhibited a 2.1-fold increased risk of bladder cancer (Ptrend = 0.04). The risk increased to 3.3 (95% CI, 1.3-8.4) among regular monthly users of ≥15 years (13). This current study is the third largest case-control study and we did not find any significant associations. Neither did all the other earlier smaller studies find overall associations (14-18). Given the proportion of exposed subjects in controls, total number of cases, and the case/control ratio, our study has 90% power to detect an increased OR of 1.46 and 80% power to detect an increased OR of 1.39.

Based on these results and the very modest increase of bladder cancer risk—slightly above unity—in hair care professionals, it seems that personal hair dye use does not cause an appreciable increase in bladder cancer risk. However, a possibility of increased risk in certain subgroups cannot be rued out given the nonsignificant increased risk in users of dark-colored dyes. Further, the overall lack of association does not exclude possible increased risk in certain genetic susceptible subpopulations (19).

As this is a hospital-based case-control study, selection bias is a potential limitation. To control for confounding from variables that could possibly correlate with hair dye use habits, we further adjusted education level and total household income in the multivariate model. The similar nonsignificant results were obtained. As bladder cancer cases were recruited from a large referral center, invasive bladder cancer subtype is overrepresented in the study population (~45.0% of cases have invasive disease). It should also be noted that the small sample size in stratified analyses results in unstable risk estimates with rather wide confidence intervals. Further, although this is a large study, only a small percentage of subjects are regular hair dye users. For example, the percentages of regular users are 26.1% in cases and 26.5% in controls.

Our study has the strength of collecting data on hair dye type, duration of use, frequency of use, and color of use. Very few previous studies collected similarly detailed information (13). As one of the largest studies examining personal hair dye use and bladder cancer risk, our study provides valuable data for future meta-analyses to further address the putative associations.


   Footnotes
 
Grant support: National Cancer Institute grants CA 74880 and CA 91846.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 2/27/06; revised 6/ 2/06; accepted 7/12/06.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. La Vecchia C, Tavani A. Epidemiological evidence on hair dyes and risk of cancer in humans. Eur J Cancer Prev 1995;4:31–43.[Medline]
  2. Ames BN, Kammen HO, Yamasaki E. Hair dyes are mutagenic: identification of a variety of mutagenic ingredients. Proc Natl Acad Sci U S A 1975;72:2423–7.[Abstract/Free Full Text]
  3. Sontag JM. Carcinogenicity of substituted-benzenediamines (phenylenediamines) in rats and mice. J Natl Cancer Inst 1981;66:591–602.[Medline]
  4. La Vecchia C, Tavani A. Hair dyes and bladder cancer: an update. Eur J Cancer Prev 2001;10:205–8.[Medline]
  5. Takouche B, Etminan M, Montes-Martinez A. personal use of hair dyes and risk of cancer: a meta-analysis. JAMA 2005;293:2516–25.[Abstract/Free Full Text]
  6. Huncharek M, Kupelnick B. Personal use of hair dyes and risk of bladder cancer: results of a meta-analysis. Public Health Rep 2005;120:31–8.[Medline]
  7. Wu X, Gu J, Grossman HB, et al. Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle-control genes. Am J Hum Genet 2006;78:464–79.[CrossRef][Medline]
  8. Hartge P, Hoover R, Altman R, et al. Use of hair dyes and risk of bladder cancer. Cancer Res 1982;42:4784–7.[Abstract/Free Full Text]
  9. Zhang Y, Holford TR, Leaderer B, et al. Hair-coloring products and risk of Non-Hodgkin's lymphoma: a population-based case-control study in Connecticut. Am J Epidemiol 2004;159:148–54.[Abstract/Free Full Text]
  10. Andrew A, Schned AR, Heaney JA, Karagas MR. Bladder cancer risk and personal hair dye use. Int J Cancer 2004;109:581–6.[CrossRef][Medline]
  11. Henley SJ, Thun MJ. Use of permanent hair dyes and bladder-cancer risk. Int J Cancer 2001;94:903–4.[CrossRef][Medline]
  12. Dinney CP, McConkey DJ, Millikan RE, et al. Focus on bladder cancer. Cancer Cell 2004;6:111–6.[CrossRef][Medline]
  13. Gago-Dominguez M, Castelao E, Yuan JM, Yu MC, Ross RK. Use of permanent hair dyes and bladder cancer risk. Int J Cancer 2001;91:575–9.[CrossRef][Medline]
  14. Hennekens CH, Speizer FE, Rosner B, Bain CJ, Belanger C, Peto R. Use of permanent hair dyes and cancer among registered nurses. Lancet 1979;1:1390–3.[CrossRef][Medline]
  15. Howe GR, Burch JD, Miller AB, et al. Tobacco use, occupation, coffee, various nutrients, and bladder cancer. J Natl Cancer Inst 1980;64:701–13.[Medline]
  16. Stavraky KM, Clarke EA, Donner A. A case-control study of hair-dye use and cancers of various sites. Br J Cancer 1981;43:236–9.[Medline]
  17. Ohno Y, Aoki K, Morrison AS. Case-control study of urinary bladder cancer in metropolitan Nagoya. J Natl Cancer Inst Monogr 1985;69:229–34.[Medline]
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  19. Gago-Dominguez M, Bell DA, Watson MA, et al. Permanent hair dyes and bladder cancer: risk modification by cytochrome P4501 A2 and N-acetyltransferases 1 and 2. Carcinogenesis 2003;24:483–9.[Abstract/Free Full Text]



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Cancer Research Clinical Cancer Research
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Molecular Cancer Research Cancer Prevention Research
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