In the United States, the incidence of bladder cancer has increased more than 50 percent during the past two decades, while the mortality rate has shown steady decline.46
In 2008, the United States reported an estimated 69,000 new cases with 14,000 deaths.46
Known risk factors for transitional bladder carcinoma include cigarette smoking, occupational exposure to aromatic amines, and urinary tract infection with Schistosoma haematobium
Structural similarities between the aromatic amines used in industrial dyes and the commercially available hair dyes, especially those sold before the 1980s, instigated numerous epidemiological studies into this subject.47
To date, three published meta-analyses have examined the epidemiological evidence relating personal hair dye use to the risk of bladder cancer. Of the three, one study found a significant relationship to hair-dye use and bladder cancer, whereas two did not.
Huncharek et al48
combined data from six case-controlled studies and one cohort between the years 1980 and 2001 and did not find an association between bladder cancer and hair dye.48
Initial pooling of the data from the seven studies yielded a nonsignificant relative risk (RR) of 1.01 (95% confidence interval [CI]: 0.92–1.11) for any type of hair dye use. However, the data were re-evaluated after excluding three studies. Studies by Altekruse et al,60
Stavraky et al,61
and Howe et al62
were eliminated for three reasons. First, the cohort by Altekruse et al was eliminated because cancer mortality rather than cancer incidence was used as the study endpoint. Superficial bladder cancer is often nonfatal and cancer mortality may not reflect the total number of cancers associated with hair-dye use. Second, the study by Stavraky et al was eliminated because urinary tract cancers were not stratified based on anatomic location. As a result, the data represented combined risk of bladder cancer and other neoplasms of the kidney. Finally, the study by Howe et al was eliminated due to small study population. Pooled analysis excluding these studies produced a statistically significant RR of 1.50 (95% CI: 1.30–1.98) for any type of hair-dye use. Based on these results, Huncharek et al concluded that a positive association existed between personal use of hair dye and bladder malignancy.
In direct contrast to the findings above, there have been two additional investigations that negate the association between hair-dye use and bladder malignancy. Takkouche et al49
combined the data from nine case-controlled studies and one cohort between the years 1977 and 2004. Ultimately, they included three case-controlled studies that were not incorporated into the meta-analysis by Huncharek et al. In addition, the cohort study was updated with a longer follow up. They did not observe an association between hair-dye use and risk of bladder cancer (RR 1.01, 95% CI: 0.89–1.14). Furthermore, RR remained nonsignificant despite stratification based on permanent hair-dye application and intense dye exposures, defined as greater than 200 lifetime exposures to hair dyes.
A more recent meta-analysis by Kelsh et al50
combined data from 11 case-controlled studies and one cohort study between the years 1977 and 2006. An association could not be substantiated based on the pooled data (RR 0.97, 95% CI: 0.87–1.08). RR remained nonsignificant despite stratification of the data based on permanent hair-dye use, dark-colored hair-dye use, duration of hair-dye use, and lifetime applications of hair dye.
Despite the positive correlation concluded by Huncharek et al, after selectively disregarding results from certain case-controlled studies, the bulk of the meta-analysis data does not support an association between personal hair-dye use and bladder malignancies.
In the United States, the incidence of leukemia, lymphoma, and multiple myeloma have been on the rise. The role of hair dye as an etiological agent has been explored in several epidemiological studies. One meta-analysis, combining data from 31 case-controlled studies and nine cohorts, has revealed a slight increase in risk of hematopoietic cancers for any user of hair dye (RR 1.15, 95% CI: 1.05–1.27).49
The increased risk was primarily attributed to the data in the 31 case-controlled studies (RR 1.23, 95% CI: 1.09–1.39), and the risk was more specific to men (RR 1.57, 95% CI: 1.33–1.84).
In the United States, the incidence of non-Hodgkin’s lymphoma (NHL) has risen by 80 percent from 1973 to 1997, with a three-percent increase annually. This large increase in incidence is undefined and cannot be attributed to improved diagnosis or known risk factors.51
Known risks include genetic susceptibility, primary or acquired immunosuppression, and infectious agents, such as the Epstein-Barr virus, human T-cell lymphotropic virus-I, human herpes virus 8, hepatitis C, and Helicobacter pylori.51
Lifestyle factors, such as cigarette smoking, hair-dye use, sunlight exposure, and dietary intake, have also been studied.51
Highlighting the epidemiological studies on hair dyes, two meta-analyses have demonstrated elevated risk of NHL in hair-dye users; however, this elevated risk was refuted by two recent case-controlled studies that show no such association.
Results of one meta-analysis indicate an increased risk of NHL in any hair-dye user (RR 1.23, 1.07–1.42, 95% CI).49
Correspondingly, Zhang et al53
demonstrated that any hair-dye use before 1980 had a positive association to NHL (OR 1.2, 95% CI: 1.0–1.3), primarily in women. Furthermore, the results revealed increased risk of a NHL subtype, follicular lymphoma, regardless of the year of application (OR 1.3, 95% CI: 1.0–1.6). This risk was further increased in individuals who dyed hair before 1980 and with the use of permanent or dark-colored dyes. Future research may seek to further explore these variables, namely, the use of dark and permanent hair-coloring products and the use of hair-coloring products prior to 1980, all of which have been hypothesized to be potently carcinogenic.
A case-controlled study examining the association between NHL and genetic variations in the enzyme utilized to metabolize aromatic amines, N-acetyltransferase (NAT), yielded positive results.54
Risk of NHL was not increased in users of hair dye after 1980, but prior to 1980 risk of NHL was increased four-fold in women who used permanent, dark-colored dyes for greater than 15 years (OR 3.9, 95% CI: 1.2–12.5). However, stratification based on NAT subtype revealed an increased risk in women who were NAT2 rapid or intermediate acetylators. Among the NAT2 rapid/intermediate acetylators, the highest risk was observed in subjects exposed to dark-colored, permanent dye with greater than five applications per year, in subjects with greater than five years of hair-dye application, and in those with more than 25 cumulative hair-dye applications. In addition, permanent hair dye used before 1980 in women who are homozygous or heterozygous for the NAT1*10 allele revealed an increased risk of NHL compared to women without the NAT1*10 allele. This risk was more pronounced with dark-colored permanent dyes. These results suggest that there may be a genetic predisposition toward development of NHL in certain subsets of hair-dye users.
In the United States, the incidence of Hodgkin’s lymphoma (HL) is on the decline and has decreased more than 16 percent from 1973 to 1996.55
The mortality rate has plummeted even more with a 65-percent decline over the same period, and an annual decrease of four percent, secondary to the advent of effective therapeutic regimens.55
Known risk factors for HL are genetic susceptibility, Epstein Barr virus, and acquired immunodeficiency syndrome.55
Postulated associations with occupational exposures have not been verified. On personal hair-dye use, the meta-analysis by Takkouche et al49
did not reveal a significant increased risk when stratifying for HL (RR 0.88, 95% CI: 0.54–1.42).
In the United States, the incidence of leukemia has been stable.52
Known risk factors include exposure to ionizing radiation, electromagnetic fields, chemotherapeutic agents, and viral agents. Occupational exposures to formaldehyde, benzene, and dioxins as well as agricultural pesticides and herbicides have also been associated with increased risk.52
The risk of personal exposure to hair dye was assessed by a meta-analysis by Takkouche et al.49
Stratification of data on leukemia did not reveal a significant increased risk (RR 1.12, 95% CI: 0.94–1.34).
Multiple myeloma is observed most often in the elderly. In the United States, the incidence of multiple myeloma is on the rise due to an increasing elderly population.52
Occupational exposure to chemicals, such as pesticides, fertilizers, petrochemicals, and wood dust, have been associated with increased risk.52
On personal hair-dye use, the meta-analysis by Takkouche et al demonstrated no increased risk of multiple myeloma in ever users of hair dye (RR 1.11, 95% CI: 0.95–1.31).49
In summary, the authors can extrapolate that there is likely an increased risk of developing NHL in hair-dye users. Also, the data show that the number of hair-dye applications and the darker colored dyes increase risk of malignancy.
Breast cancer is the most common noncutaneous female malignancy in the United States with 182,460 new cases diagnosed each year. The rising incidence of breast cancer is thought to be due to increased detection with screening mammography, and the incidence of mortality has drastically declined over the past three decades. Risk factors for breast cancer are multifactorial and include age, gender, ethnicity, history of benign breast disease, previous history of breast cancer, family history, genetic influences, reproductive and hormonal factors, exposure to ionizing radiation, lifestyle and dietary habits, and environmental exposures. The association between hair dye and breast cancer was explored in the meta-analysis by Takkouche et al.49
Data pooled from 12 case-controlled studies and two cohort studies did not reveal a significant association between female breast cancer and any hair-dye users (RR 1.06, 95% CI: 0.95–1.18), permanent dye users (RR 1.00, 95% CI: 0.94–1.05), or users with more than 200 lifetime exposures to hair dye (RR 0.99, 95% CI: 0.89–1.11).
Interestingly, a population-based, case-controlled study by Ambrosome et al,56
which sought to detect the presence of carcinogenic-DNA adducts in exfoliated breast ductal epithelial cells, showed a positive association between the presence of carcinogenic adducts and the use of light-colored hair dye (OR 18.12, 95% CI: 1.45–226.83). This is a surprising finding because light-colored hair dye is theoretically less carcinogenic because it causes less destruction to the hair shaft than darker shades. The use of hair dye at least once in the last six months was also an independent risk factor.
A meta-analysis by Takkouche et al49
pooled data on brain tumors, skin cancer, ovarian cancer, and cervical cancer. Two studies per site were analyzed.49
The risk was nonsignificant for skin cancer (0.89, 95% CI: 0.53–1.9), ovarian cancer (RR 0.74, 95% CI: 0.51–1.07), and cervical cancer (RR 0.89, 95% CI: 0.53–1.9), but significance was observed for brain tumors (RR 1.83, 95% CI: 1.16–2.89) and ovarian cancer (RR 1.71, 95% CI: 1.15-2.53). These significant findings are questionable because they are based on small case-controlled studies.
Parental exposure and risk of malignancy in the unborn child.
Understanding the malignant potential of hair-dye products when used during pregnancy is of great importance due to the possible risk of exposure to the unborn child. Of the four case-controlled studies examined, three demonstrate a positive relationship between cancer development and hair-dye exposure. McCall et al57
explored the association between maternal hair-dye use and the risk of neuroblastoma in the offspring. They concluded that maternal hair-dye use a month before conception and throughout pregnancy increased risk of neuroblastoma in the offspring (OR 1.6, 95% CI: 1.2–2.22). Risk stratification based on hair-dye type revealed a greater risk for maternal use of temporary hair dyes, rather than use of permanent hair dyes. This is a surprising finding, as the use of permanent hair dye has been more consistently associated with carcinogenesis, and temporary hair dye does not penetrate the hair shaft.
Another study showed significant risk of childhood brain tumors in offspring of mothers using hair dye within five years of childbearing after 1980.63
Once again, this finding contradicts previous data, which has shown increased risk with dye exposure prior to 1980. These studies suggest there may be harm to the baby in utero
and therefore pregnant patients should be warned about possible carcinogenesis. Thus, it is the authors’ current recommendation that pregnant patients avoid all hair coloring products.
Finally, Chen et al58
conducted a case-controlled study examining the relationship between exposure to pesticides, chemicals, dusts, fumes, metals, hair dye, and the development of childhood germ-cell tumors.58
Maternal use of hair dye during breastfeeding increased risk of childhood germ-cell tumors (OR 1.5, 95% CI: 1.0–2.2), primarily in girls. Maternal use of hair dye one month prior to pregnancy was associated with an increased risk of tumors in boys.
In 1994, Bunin et al59
published a population-based case-control study of 321 cases of childhood astrocytic glioma or primitive neuroectodermal tumors of the brain with 321 age-matched controls. Maternal use of hair-coloring products during pregnancy was not associated with childhood development of astrocytoma (OR 0.7, 95% CI: 0.3–1.6) or primitive neuroectodermal tumors of the brain (1.1, 95% CI: 0.4–2.6).