Hair Dye Use and Risk of Adult Acute Leukemia

Transcription

1 American Journal of Epidemiology Copyright 2004 by the Johns Hopkins Bloomberg School of Public Health All rights reserved Vol. 160, No. 1 Printed in U.S.A. DOI: /aje/kwh166 Hair Dye Use and Risk of Adult Acute Leukemia Garth H. Rauscher 1, David Shore 2, and Dale P. Sandler 2 1 Division of Epidemiology and Biostatistics, University of Illinois, Chicago, IL. 2 National Institute of Environmental Health Sciences, Research Triangle Park, NC. Received for publication September 5, 2003; accepted for publication January 16, Certain chemicals in hair dyes are known animal carcinogens. Darker, more permanent, and earlier dye formulations may be more carcinogenic than other dye types. For 769 adult acute leukemia cases and 623 population-based controls in a US and Canadian case-control study in , the authors asked separately about use of permanent and nonpermanent (semipermanent and temporary) hair dye use. Use was reported by 45% of women and 6% of men. There was a modest positive association for ever use of permanent dyes (odds ratio = 1.5, 95% confidence interval: 1.0, 2.1), which was stronger for long duration (15 or more years) of use (odds ratio = 1.8, 95% confidence interval: 1.0, 3.1). The greatest odds ratio was for 15 or more years of using hair dyes up to six times per year (odds ratio = 2.4, 95% confidence interval: 1.0, 5.8); the corresponding odds ratio for use six or more times a year was lower, suggesting the possibility of misclassification of dye type among frequent users, since nonpermanent dyes tend to be used more frequently than permanent dyes. Nonpermanent dyes were not associated with risk. Long duration of permanent dye use may have a larger impact on the risk of adult acute leukemia and other hematopoietic cancers than prior epidemiologic data suggest. case-control studies; hair dyes; leukemia; measurement Abbreviations: CALGB, Cancer and Leukemia Group B; CI, confidence interval. Through the years, hair dyes have contained mutagenic and carcinogenic chemicals, and concern has been raised about the potential cancer risks associated with hair dye use (1, 2). Hair dye use has been examined as a risk factor for breast cancer (3 5), endometrial cancer (5), and urinary tract cancer (6, 7), and associations have been either lacking or marginal and based on sparse data. Epidemiologic studies have suggested the existence of positive associations with myelodysplasia (8), multiple myeloma (9 11), leukemia and preleukemia (12, 13), non-hodgkin s lymphoma (11, 13), and Hodgkin s disease (11), while other studies have failed to find associations (14, 15). Various factors might affect cancer risk related to hair dye use. Permanent dyes contain greater amounts of carcinogenic and mutagenic chemicals than semipermanent or temporary dyes, and darker dyes contain greater amounts of carcinogenic and mutagenic chemicals than lighter dyes (11). Older dyes may also be more carcinogenic than newer dyes formulated in response to concern about potential cancer risk. Frequency and duration of use are also likely to affect risk, as are the chemical processes involved (e.g., use of peroxide to lift color in dying from dark colors to light) and the percentage of hair that is gray and in need of color (for those using dyes to cover gray). In a large case-control study of adult leukemia patients and population-based, random digit dialed controls, we examined the role of hair dyes in the risk of adult acute leukemia. MATERIALS AND METHODS Patient and control recruitment Patient and control recruitment and data collection procedures have been described in detail elsewhere (16, 17). Briefly, at the time of diagnosis, incident cases of adult acute leukemia were recruited through Cancer and Leukemia Group B (CALGB), a multiinstitutional cooperative cancer treatment group located throughout the United States and Canada. Approval for the study was obtained from the National Institute of Environmental Health Sciences institutional review board (National Institutes of Health) and the Correspondence to Dr. Garth Rauscher, Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois, 816 SPHPI (M/C 923), 1603 W. Taylor Street, 8th Floor, Chicago, IL ( garthr@uic.edu). 19

2 20 Rauscher et al. institutional review boards at participating CALGB institutions. Patients were in effect excluded from the case-control study if their disease was known to be secondary to chemotherapy or radiotherapy or the result of a preleukemic condition, such as myelodysplasia, because of requirements for ongoing CALGB clinical trials. Between January 1986 and June 1989, 811 adult acute leukemia patients were enrolled (84 percent total response). Hospitalized patients were contacted by telephone within a few days of diagnosis, at which time the telephone interview was completed or a later time was arranged. Next of kin participated in 34 percent of case interviews; 21 percent were without patient involvement, and the remaining 13 percent included the patient. Control subjects were selected using a two-stage random digit dialing procedure with the sampling frame restricted to the area code and first three digits of the patients telephone numbers. were identified within 6 months of case accrual and were frequency matched to cases by age in 10- year intervals (reference date was age at diagnosis for cases and age at interview for controls), sex, race (White vs. other), and region of residence within the United States and Canada (six regions were defined). Screening was completed for 792 potential controls (83 percent). Of those screened and eligible, 637 (80 percent) completed telephone interviews for an overall response rate of 66 percent. Proxy interviews were conducted for 83 (13 percent) of the controls. Interviews were completed within 6 months of matching to cases, resulting in a reference date for controls that was 6 12 months after the reference date for cases. We assumed that the resulting difference in age and exposure periods between cases and controls would have a negligible effect on odds ratio estimates. Patients and controls were interviewed by telephone using a structured questionnaire to obtain information on their medical history, family medical history, smoking, and occupational and environmental exposures. The interview took about 45 minutes to complete. Construction of hair dye exposure variables Patients and controls were asked if they had ever used hair dyes, their age at first use, and the total number of years of use. They were then asked specifically about use of permanent hair color products, products that contain peroxide so that the color does not wash out but leaves a line as hair grows out. and controls were asked if they had ever used permanent dyes, how many times per year they generally used permanent dyes, how many years altogether they used permanent dyes, and the usual brand used. Patients and controls were then asked about use of temporary hair color products, which were defined as semipermanent rinses, rinses that wash out after several shampooings, dyes that wash out after one shampooing, and hair darkeners such as Grecian formula. Questions regarding semipermanent/ temporary dyes were similar in structure and design, making it possible to identify specific types of products that were used. Permanent dye users were defined as individuals reporting permanent dye use either without reporting a brand name or reporting a brand name that was consistent with permanent dyes. Because we asked about nonpermanent (semipermanent and temporary) dyes as a group, semipermanent dye use was defined as reporting nonpermanent dye use and required that the individual also report a brand name consistent with semipermanent dyes. Likewise, temporary dye use was defined with the requirement that the individual also report a brand name consistent with temporary dyes. As a result, we excluded from analyses of specific dye types 22 cases and 10 controls for whom we could not determine hair dye type. We created a variable for discrete categories of hair dye use based on preexisting knowledge about the relative carcinogenicity of different dye types (0 = never used, 1 = temporary dye use but no semipermanent or permanent dye use, 2 = semipermanent dye use but no permanent dye use, and 3 = permanent dye use). This variable was modeled as three indicator variables with nonusers of any dye type as the referent. Separately for semipermanent and permanent dyes, frequency of use was categorized as none, 1 2, 3 5, and six or more applications per year, and duration of use was categorized as none, less than 5, 5 14, and 15 or more years. Categorizations were chosen to yield roughly equivalent sample sizes. We also created a four-category variable for decade of first use (never use, earliest use before 1970, from 1970 to 1979, and 1980 or later). Separate variables were created for semipermanent and permanent dye use. Individuals who reported using hair dyes were asked about their natural hair color (blonde, red, brown, black, or gray) and then asked to provide all dye colors that were used. We defined hair color as either light (blonde or red) or dark (brown or black), and we defined the darkness of darkest dye used as light (auburn, blond, white, frosting, and gray) or dark (brown or black). Red dyes that were considered to be more brown than red were classified as dark dyes, while the remaining red dyes were classified as light dyes. Separate variables for dye darkness were created for semipermanent and permanent dyes. Analyses Odds ratios from logistic regression models were used to estimate the relative risk of adult acute leukemia, with 95 percent confidence intervals. Models were adjusted for the study matching factors (age as six categories, race, sex, region) and education as a three-category variable (less than high school degree, high school degree, and beyond a high school degree). When modeling semipermanent and permanent dye variables separately, we excluded users of semipermanent, temporary, and unknown dye types from the analyses of permanent dyes, and we excluded users of permanent, temporary, and unknown dye types from the analyses of semipermanent dyes. We ran separate models for the variables: 1) ever use, 2) number of uses per year, 3) duration of use, and 4) earliest decade of use. Then, we estimated odds ratios for the darkest dye used both overall and stratified by natural hair color. Women reporting their hair color as gray (n = 10) were excluded from analyses stratified by natural hair color. In general, permanent dyes tend to be used less frequently than nonpermanent dyes. We hypothesized that the duration effect for permanent dyes might be stronger among those reporting less (rather than more) frequent permanent dye

3 Hair Dye Use and Risk of Adult Acute Leukemia 21 use, since those reporting greater frequency might be reporting about nonpermanent dye use, especially the use of temporary dyes and rinses. Therefore, we repeated the analyses of duration of dye use after excluding those reporting high frequency of use (six or more times per year) and then again after excluding those reporting low frequency of use (1 5 times per year). Analyses were performed separately for permanent and semipermanent dyes. In secondary analyses, rather than excluding multiple dye users, we included all users and mutually adjusted for each dye type in the same models. The results from these models were similar to the results from the main analyses and are not presented. Finally, we stratified the odds ratio estimates for ever use of permanent dyes by demographic characteristics to examine the potential impact of selection bias on odds ratio estimates resulting from differential selection of cases and controls by demographic factors. There were 1,392 individuals (769 cases and 623 controls) with complete data on the study matching factors, education, and ever-never history of hair dye use that are included in analyses of ever versus never use of any type of hair dye. All logistic regression models were performed in SAS version 8 software, using the LOGISTIC procedure (SAS Institute, Inc., Cary, North Carolina). RESULTS Patient and control demographics and controls were very similar in terms of the matching variables age, race, gender, and geographic region: 37 percent were less than 40 years, 32 percent were years, and 31 percent were 60 or more years of age at diagnosis (cases) or interview (controls); 88 percent were Caucasian and 59 percent were male. Finally, 58 percent were recruited from the Northeast region of the United States and Canada. Of cases, 77 percent were myelocytic, 16 percent were lymphocytic, and 7 percent were mixed or other types of acute leukemia. Distribution of hair dye use Forty-five percent of women and 6 percent of men reported hair dye use. The largest combination of hair dye types used was permanent dye only (10 percent), followed by semipermanent only (6 percent) (table 1). Approximately 2 percent reported use of both permanent and semipermanent dyes. Among those defined as permanent dye users, 68 percent reported a brand name consistent with permanent dyes. The percentage that reported a brand name did not vary appreciably by case-control status. Ever use, frequency, and duration For ever use of any hair dye, the odds ratio was 1.3 (95 percent confidence interval (CI): 0.99, 1.8). Using the variable for discrete categories of use, ever use of permanent dyes was associated with a 50 percent increased risk, while neither semipermanent nor temporary dyes were associated with risk (table 2). In analyses excluding users of multiple TABLE 1. Distribution of hair dye use among cases and controls in a case-control study of adult acute leukemia risk, United States and Canada, dye types, ever use of permanent dye was associated with a 60 percent increased risk, while ever use of semipermanent dyes was not associated with risk (table 3). For permanent dyes, the odds ratio differed little by frequency and increased with duration of use in years. Decade of first use Dye type No. % None 1, Any hair dye use Permanent alone Permanent + semipermanent Permanent + temporary Semipermanent alone Semipermanent + temporary Temporary alone Unknown dye type Total 1, First use of permanent dyes before 1970 was associated with a 70 percent increased risk, and the odds ratio remained marginally elevated for dye use beginning in the 1970s. Permanent dye use beginning in 1980 or beyond was not associated with risk (table 3). First use of semipermanent dyes before 1970 was marginally associated with a 60 percent increased risk but was not associated with risk after 1970 (table 3). TABLE 2. Risk of adult acute leukemia by most permanent dye type ever used in a case-control study of adult acute leukemia risk, United States and Canada, Categories Ever use (n = 1,392) No hair dye use Permanent OR* 95% CI* Any hair dye use , 1.8 Discrete categories of use (n = 1,360) No hair dye use Temporary dyes only , 2.1 Semipermanent but no permanent dyes , 1.7 Permanent dyes regardless of other use , 2.2 * OR, odds ratio (adjusted for matching factors, i.e., age, race, sex, and geographic region, as well as for education in logistic regression); CI, confidence interval. A total of 22 cases and 10 controls with unknown dye types were excluded from analyses of the hierarchical variable.

4 22 Rauscher et al. TABLE 3. Risk for permanent-only and semipermanent-only dye use compared with never use of any dye type in a case-control study of adult acute leukemia risk, United States and Canada, Ever use Risk by dye color and hair color Permanent dye use only OR* Semipermanent dye use only * OR, odds ratio (adjusted for matching factors, i.e., age, race, sex, and geographic region, as well as for education in logistic regression); CI, confidence interval. Number of cases and controls either missing data on specific hair dye use variable or excluded from analyses because they reported using more than one dye type. Light = blonde or red, and dark = brown or black. 95% CI* Never Risk for duration of use stratified by frequency of use OR 95% CI Ever , , 1.7 Excluded Frequency (times/year) < , , , , , , 1.7 Excluded Duration (years) < , , , , , , 2.0 Excluded Decade of first use Never Before , , , , 1.9 After , , 1.2 Excluded Dye color Never used Light , , 1.5 Dark , , 2.1 Both , , 4.9 Excluded Compared with the risk for never users of hair dye, the odds ratio associated with permanent dye use was greatest for use of light permanent dyes only, followed by dark dyes only, and the lowest for use of both light and dark permanent dyes (table 3). No large differences in effect were observed when separating the effects of darkness of permanent dyes for subjects with light versus dark hair (results not shown). Semipermanent dyes were not associated with risk regardless of dye color or hair color. For individuals reporting permanent dye use 1 5 times per year, the effect of duration of permanent dye use was stronger than it was for all permanent dye users as a group, reaching an odds ratio of 2.4 for 15 or more years of use (table 4). Among those who reported permanent dye use more than six times per year, there was no association with increasing duration of use (results not shown). Regardless of frequency of use, increasing duration of semipermanent dye use was not associated with risk.

5 Hair Dye Use and Risk of Adult Acute Leukemia 23 TABLE 4. Risk for duration of hair dye use after excluding high annual frequencies of use (six or more times per year), separately for permanent and semipermanent dyes, in a case-control study of adult acute leukemia risk, United States and Canada, Duration (years of use) Permanent dye use only OR* 95% CI* Semipermanent dye use only Never OR 95% CI , , , , , , 3.4 Risk by leukemia subtype When stratified by leukemia subtype, ever use of permanent hair dyes was associated with an odds ratio of 1.6 (95 percent CI: 1.1, 2.5) for myelocytic leukemia (515 cases), and the trends in risk with duration and frequency were similar to the trends observed for all leukemia subtypes combined. For lymphoblastic leukemia (109 cases), the odds ratio for ever use of permanent dyes was 2.0 (95 percent CI: 0.87, 4.6). There was a suggestion of a dose response for both duration and frequency, with the odds ratio reaching 4.6 (95 percent CI: 1.5, 14) for 15 or more years of use and the odds ratio reaching 3.8 (95 percent CI: 1.2, 12) for six or more applications per year. Ever use of permanent dyes was not associated with mixed lineage and other leukemia subtypes combined (n = 49). Stratification of risk by demographic factors The odds ratio associated with ever use of permanent dyes was greater for individuals with less income and less education (table 5). The odds ratio was also greater for older individuals as well as for men compared with women, although the estimate for men was unstable. Additional analyses Additional adjustment for cumulative smoking exposure, residential and occupational solvent exposures, aromatic hydrocarbon exposure specifically, and history of diagnostic ionizing radiation did not materially change the hair dye use odds ratio estimates (results not shown). Exclusion of proxy interviews (34 percent for cases and 13 percent for controls) did not appreciably alter any of the results presented (results not shown). DISCUSSION * OR, odds ratio (adjusted for matching factors, i.e., age, race, sex, and geographic region, as well as for education and dye type in logistic regression; users of all other dye types were excluded from separate analyses of permanent and semipermanent dyes); CI, confidence interval. This is the largest case-control study to date of the association between permanent and semipermanent hair dyes and the risk of adult acute leukemia, and these analyses provide some evidence in support of hair dye exposure as a potential risk factor for this cancer. Previous case-control studies have suggested the existence of an increased risk for a variety of hematopoietic cancers, including leukemia and preleukemia (1, 2), multiple myeloma (3, 4), myelodysplasia (5), non- Hodgkin s lymphoma (6, 7), and Hodgkin s disease (8). Results have often been based on sparse data, and odds ratios have ranged roughly from 1.5 to about 4. In contrast, two large cohort studies The Nurses Health Study and American Cancer Society cohorts failed to find consistent associations between hair dye use and hematopoietic cancer risk and mortality (14, 15). The American Cancer Society cohort study did report marginally increased relative mortality for non-hodgkin s lymphoma and multiple myeloma related to longer duration of dark permanent dye use (15). Although case-control studies are potentially limited by recall biases that could produce a spurious positive association, cohort studies measure hair dye use at the beginning of follow-up, when individuals are younger and less likely to be dying their hair. The American Cancer Society cohort study included exposure assessment at baseline only and at an average age of 56 years, before many individuals begin to dye their hair (15). In the Nurses Health Study (14), hair dye use was established at baseline in 1976 and biannually for the first 6 study years, while person-time for the remaining 8 years was assigned to the exposure category in Individuals who began using dyes after 1982 would have been misclassified as nonusers. In both studies, misclassification of subsequent hair dye use would have attenuated associations with hair dye use. Our results are consistent with a greater carcinogenicity for earlier dye formulations. However, the absence of an observed increase in risk among those whose first use was more recent may simply be a reflection of lower cumulative exposure or insufficient time since first exposure for risk to become apparent. Furthermore, the effect of total years of use could be driving the apparent effect of earlier decade of first use; the two effects could not be separated because of the sparseness of data upon cross-classification. In contrast to expectation, differences by color were not observed, although the odds ratio was greatest for light dyes. High-peroxide permanent products used to strip dark hair to color it blonde may have equal or greater carcinogenic potential than light dyes used to color light hair. Inconsistent with this notion, however, we found a stronger association for use of light permanent dyes among light-haired individuals than among dark-haired individuals. A limitation of our analyses of dye darkness was that we did not collect informa-

6 24 Rauscher et al. TABLE 5. Distribution of ever use of permanent hair dyes by demographic characteristics, to gauge the potential impact of selection factors on risk for permanent dye use, in a case-control study of adult acute leukemia risk, United States and Canada, Permanent dye use Demographic characteristics (%) (%) Crude OR 95% CI Education < High-school degree , 6.6 High-school degree , 3.0 > High-school degree , 2.5 Annual income ($) <10, , ,000 29, , ,000 49, , , , 3.7 Smoking status Never smoker , 2.4 Ever smoker , 2.9 Age (years) < , , ** 6* , 5.7 Gender Female , 2.2 Male *** 0.3*** , 71 * p < 0.1; ** p < 0.01; *** p < A total of 78 cases and 48 controls were missing data on income, and one case was missing information on smoking status. OR, odds ratio; CI, confidence interval (both from logistic regression). tion on duration and frequency of use for separate dye colors; therefore, among individuals reporting more than one dye color, we could not determine whether the darkest dye used was used the majority of the time or not. Furthermore, although we defined brown dyes as dark dyes, they in fact cover a wide range of shades, with different chemicals and chemical concentrations, some of which include what could be considered light dyes. We also attempted to distinguish between light (more blonde) and dark (more brown) shades of red dye, but considerable misclassification is likely. In the present study, permanent dye use was modestly associated with increased risk, and longer duration of use was associated with increased risk. In contrast, it appeared that lower frequency of use was more strongly associated with increased risk, for permanent and (marginally) for semipermanent dyes. Because permanent dye users may be unlikely to dye their hair more than about once every 6 8 weeks, individuals who report a high frequency of permanent dye use may in truth be reporting about nonpermanent dyes, especially temporary rinses. When we restricted permanent dye use to frequencies that were most consistent with actual permanent dye use (less than six applications per year), we observed an apparent dose-response effect for increasing duration of permanent dye use. These results suggest that an effect of permanent dye use on risk may be attenuated by misclassification of nonpermanent dye users as permanent dye users. Selection and recall bias Although a handful of patients agreed to participate in our study after declining to participate in a clinical trial, most of the patients included in our study were clinical trial participants. Older individuals are underrepresented in treatment trials either by design or because of more subtle influences, and we previously reported what appeared to be a preferential selection of younger patients into the present study (16). Because the odds ratio for permanent dye use was greatest in older individuals (table 5), preferential selection of younger patients into the study could have attenuated the overall odds ratio for permanent dye use, even though controls were selected to resemble the age distribution of the cases and age was taken into account in our analyses. The odds ratio (although unstable) was also greater among men than among women. Because of the small proportion of male hair dye users, however, the impact of any bias related to uneven representation by men and women would likely be small.

7 Hair Dye Use and Risk of Adult Acute Leukemia 25 Individuals with less education and income tend to be underrepresented in both treatment trials (cases) and random digit dialed telephone interviews (controls). In the present study, the odds ratio for permanent hair dye use was greatest for individuals with less education and income, but these individuals were probably underrepresented among both cases and controls. The result may have been an attenuation of the odds ratio from an elevated distribution of socioeconomic status in cases and controls, despite adjusting for education in our analyses. Because hair dye use is not a well-known cause of leukemia and was one of many exposures we asked about, it is not likely that recall of hair dye use was differential for cases and controls. For this reason, recall bias would be an unlikely explanation for the positive association for permanent dye use, especially given the lack of an association for nonpermanent dye use. However, it is likely that there is a considerable amount of misclassification of hair dye use by duration and type, in general. Such misclassification would tend to make it more difficult for us to identify risks associated with hair dye use. Conclusion Longer duration of permanent dye use appears to increase the risk of adult acute leukemia, and misclassification of nonpermanent dye users as permanent dye users may be producing an underestimate of the odds ratio for permanent dyes. If the proposed pattern of dye misclassification exists in this study and in other case-control studies of hematopoietic cancer, use of permanent hair dyes may have a somewhat larger impact on risk of adult acute leukemia and hematopoietic cancer than prior epidemiologic data suggest. REFERENCES 1. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Occupational exposures of hairdressers and barbers and personal use of hair colourants; some hair dyes, cosmetic colourants, industrial dyestuffs and aromatic amines. Proceedings. Lyon, France, 6 13 October IARC Monogr Eval Carcinog Risks Hum 1993;57: Hair dye and cancer. Health News 2001;7:8. 3. Koenig KL, Pasternack BS, Shore RE, et al. Hair dye use and breast cancer: a case-control study among screening participants. Am J Epidemiol 1991;133: Shore RE, Pasternack BS, Thiessen EU, et al. A case-control study of hair dye use and breast cancer. J Natl Cancer Inst 1979; 62: Stavraky KM, Clarke EA, Donner A. Case-control study of hair dye use by patients with breast cancer and endometrial cancer. J Natl Cancer Inst 1979;63: Miller AB, Bartsch H. Hair dye use and bladder cancer. Int J Cancer 2001;94: Nomura A, Kolonel LN, Yoshizawa CN. Smoking, alcohol, occupation, and hair dye use in cancer of the lower urinary tract. Am J Epidemiol 1989;130: Nagata C, Shimizu H, Hirashima K, et al. Hair dye use and occupational exposure to organic solvents as risk factors for myelodysplastic syndrome. Leuk Res 1999;23: Brown LM, Everett GD, Burmeister LF, et al. Hair dye use and multiple myeloma in white men. Am J Public Health 1992;82: Herrinton LJ, Weiss NS, Koepsell TD, et al. Exposure to haircoloring products and the risk of multiple myeloma. Am J Public Health 1994;84: Zahm SH, Weisenburger DD, Babbitt PA, et al. Use of hair coloring products and the risk of lymphoma, multiple myeloma, and chronic lymphocytic leukemia. Am J Public Health 1992; 82: Mele A, Szklo M, Visani G, et al. Hair dye use and other risk factors for leukemia and pre-leukemia: a case-control study. Italian Leukemia Study Group. Am J Epidemiol 1994;139: Cantor KP, Blair A, Everett G, et al. Hair dye use and risk of leukemia and lymphoma. Am J Public Health 1988;78: Grodstein F, Hennekens CH, Colditz GA, et al. A prospective study of permanent hair dye use and hematopoietic cancer. J Natl Cancer Inst 1994;86: Altekruse SF, Henley SJ, Thun MJ. Deaths from hematopoietic and other cancers in relation to permanent hair dye use in a large prospective study (United States). Cancer Causes Control 1999;10: Rauscher GH, Sandler DP, Poole C, et al. Family history of cancer and incidence of acute leukemia in adults. Am J Epidemiol 2002;156: Sandler DP, Shore DL, Anderson JR, et al. Cigarette smoking and risk of acute leukemia: associations with morphology and cytogenetic abnormalities in bone marrow. J Natl Cancer Inst 1993;85: