Document ganwVzEG8Kk03jpVGvwg61O7a

FILE NAME: Talc (TALC) DATE: 1992 DOC#: TALC029 DOCUMENT DESCRIPTION: Journal Article - Mineral Fiber Exposure and the Development of Ovarian Cancer GYNECOLOGIC ONCOLOGY 4 5 , 20-25 (1992) The material on this page was copied from the collection of the National Library of Medicine by a third party and may be protected by U S Copyright law Mineral Fiber Exposure and the Development of Ovarian Cancer K arin A. R osenblatt, Ph.D ., M oyses S z k l o , M .D ., D r.P.H.,* N eil B. R osenshein, M.D.* t 'Department o f Epidemiology. The Johns Hopkins School o f Hygiene and Public Health, Baltimore, Maryland 21218; and t Department of Gynecology and Obstetrics, The Johns Hopkins Hospital, Baltimore, Maryland 21218 Received July 10, 1991 A hospital-based case-control study of the association between fiber exposure and the development of epithelial ovarian cancer was performed at the Johns Hopkins Hospital in Baltimore, Mary land. Genital and respiratory fiber exposures were ascertained from incident cases (N = 77) and age-race matched controls (N - 46) using a structured questionnaire. Cases were ascertained between 1981 and 1985. An increased risk was observed for ex posure to talc on sanitary napkins (OR = 4.79, 95% C l = 1.29 17.79), genital fiber exposure from different sources for a long (cumulative exposure >37.4 years) length of time (OR = 2.35, 95%>C l = 0.95-5.80), and occupational fiber exposure in relatives (OR -- 2.81, 95% C l = 0.90-8.75). A negative association was observed for antecedent tubal ligation (OR = 0.15, 95% Cl = 0.027-0.88). Findings from this study should be confirmed in larger investigations. 1992 Academic Press. Inc INTRODUCTION Occupational exposure to asbestos has been identified as a risk factor for ovarian cancer in several studies [1 3]. Similarly, fiber-containing substances, such as talc, have also been implicated as risk factors [4-9], A matched case-control study of epithelial ovarian cancer was con ducted, in which the role of both genital and respiratory sources of fiber was assessed, to confirm these findings. STUDY POPULATION Cases and controls were ascertained from the Johns Hopkins Hospital between 1981 and 1985. This analysis is restricted to the 77 cases who were matched to 46 hospital controls and treated for conditions other than gynecologic or malignant diseases. Originally 140 newly diagnosed cases of epithelial ovarian cancer who met the Present address: Department of Health and Safety Studies. Uni versity of Illinois at Urbana-Champaign, 120 Huff Hall, 1206 S. Fourth St., Champaign, IL 61820 (Correspondence to Dr. Rosenblatt at this address). eligibility criteria were ascertained from the Johns Hop- ' kins Hospital. One hundred eight (77.1%) of these cases were successfully interviewed. These cases were diag nosed within 6 months of admission, were pathologically confirmed by examination of the ovaries, were admitted as in-patients for treatment or diagnosis, and were resi dents of the United States. Controls were in-patient fe- 1 males without gynecologic or malignant conditions who were initially matched to cases by age (within 5 years), race, and date of diagnostic admission (within 1 year).* Since it was difficult to find controls meeting all of the * matching criteria, a control could not be found for all * cases. Unmatched cases were therefore matched a pos- s teriori to controls, to form matched triplets of 2 cases* and 1 control. A posteriori matching was performed within the same 5-year interval, by race and by closest date of diagnostic admission. The matching procedure allowed for the inclusion of 77 cases in the study. There 1 were 46 matched sets, of which 31 consisted of 2 cases and 1 control. No matched control could be found for 13 cases, which were excluded from the analysis. METHODS Data were ascertained primarily from a questionnaire that was administered to participants both by telephone il and in the hospital. Information on previous abdominal and gynecologic operations was also ascertained from medical records. ; The questionnaire elicited information on the presence i' and length of genital fiber and respiratory fiber exposure, : reproductive factors, estrogen use, family history of can- * cer in first-degree relatives, and other contraceptive use. Descriptions of the questions used to ascertain fiber ex posure are listed in Appendix 1. Fiber exposure was de fined as exposure to asbestos, talc (which may contain , asbestos), and fiberglass. ' An attempt was made to estimate the overall effect of * 0090-8258/92 SI.50 20 Copyright 1992 by Academic Press. Inc. All rights of reproduction in any form reserved.  FIBERS AND OVARIAN CANCER 21 The material on this page was copied from the collection of the National Library of Medicine by a third party and may be protected by U.S Copyright law "dose" or length of genital and respiratory fiber exposure. TABLE 1 This was accomplished by adding the number of years of Distribution of Matched Cases and Controls ' each type of genital or respiratory exposure from all sources. Since many of these exposures occurred at the Cases Controls same time, these variables should be considered as crude N Pc N %. , measures of dose rather than the true length of exposure. Conditional logistic regression [10] was used to deter Age (years) Less than 30 3 3.9 mine the strength of the association. Odds ratios were 30-39 1 1.3 calculated to describe the relationship of genital and res- 40-49 11 14.3 2 4.4 i 2.2 8 17.4 1 piratory fiber exposure to ovarian cancer. The odds ratio 50-59 21 27.3 10 21.7 is an estimate of the relative risk for relatively rare dis 60-69 35 45.4 21 45.( eases such as ovarian cancer and, in this paper, is referred 70-79 5 6.5 3 6 80 or higher 1 1.3 1 2.2 ( to as the relative risk estimate (RR). Total 77 46 The following variables were assessed as potential confounders: Race White ! 70 90.9 41 89.1 I Tobacco use Number of cigarettes per day Black Total 7 9.1 5 10.S 77 46 Ovulatory time period Number of pregnancies Cancer in mother or father If a potential confounder changed the relative risk es Obesity 1 year prior to diagnosis timate associated with a fiber exposure by more than 15% Obesity 20 years prior to diagnosis it was retained in the multivariate model. Confounder Obesity at highest weight during the 20 years prior were sequentially added to multivariate models, depend to diagnosis ing on the level with which they changed the odds rati< Obesity according to average weight during the 20 of a fiber related exposure. years prior to diagnosis Interaction between fiber exposures and potential con ) Husband's and subject's education founders was evaluated by comparing the deviance o Previous cancer models with and without the interaction term [12]. Marital status j Religion RESULTS Use of oral contraceptives Use of contraceptive foams, creams, and jellies by themselves Age and Racial Distribution : t Table 1 lists the age and racial distribution of cases an* Use of an IUD controls. Most cases and controls were in the age group 40 to 69. It was difficult to obtain controls that did nfc On the basis of the strength of their relative risk es have a chronic disease, resulting in a lower than expect^ timates and the difference in frequency with which they number of controls. 1 > were observed in cases and controls, the following vari ables were identified as potential confounders: measures Diagnoses o f Controls ? of obesity, socioeconomic status (subject's education; RR t = 0.5, 95% Cl = 0.2-1.1), and religion (Jewish, RR = Controls were selected so that they did not have thei 2.9, 95% Cl = 0.6-13.8; Catholic, RR = 0.5, 95% Cl primary diagnostic condition for more than 1 year. TabJ = 0.2-1.5), reproductive status (total live births, 1-2, 2 lists the primary diagnosis of the controls included i RR = 0.7, 95% Cl = 0.2-1.9; live births > 2, RR = the study. ; 0.4, 95% Cl = 0.2-1.3), and oral contraceptive use (OR Genital Fiber Exposure = 0.9, 95% Cl = 0.3-23.0). Obesity 1 year prior to diagnosis (RR = 2.3, 95% Cl Different sources of genital fiberexposure were ei , = 0.9-6.1), obesity 20 years prior to diagnosis (RR = amined (Table 3). Exposure from any of thepotentii 2.1, 95% Cl = 0.7-6.9), and obesity according to highest sources of genital fiber was highly prevalent (91.1% i weight during the 20 years prior to diagnosis (RR = 1.5, controls) and not found to be related to ovarian candf 95% Cl = 0.7-3.2) were also found to be potential con- (RR = 1.0, 95% Cl = 0.2-4.0). Since it was felt thi | founders. Obesity was defined as a height/weight index this index did not accurately characterize cumulative e? [ greater than that exhibited by women in the 85th per posure, the median length of exposure from all genit; centile [11] of the population. sources (with the time since tubal ligation subtracted) was  iWfrlWffr wty&ii 22 ROSENBLATT, SZKLO, AND ROSENSHEIN TABLE 2 Distribution of Matched Controls by Primary Diagnosis Diagnosis of restricted controls N% Infectious and parasitic diseases Diseases of the digestive system Opthamologic disorders Diseases of the circulatory system Symptoms, signs, and ill-defined conditions Diseases of musculoskeletal and connective tissue Diseases of the endocrine system or metabolic or immunologic disorders Diseases of the respiratory system Benign neoplasms Injury and poisoning Total 1 2.2 6 13.0 15 32.6 11 23.9 8 17.4 1 2.2 1 2.2 1 2.2 1 2.2 1 2.2 46 100.00 used to categorize the dose of genital fiber exposure. A relative risk estimate of borderline significance was seen for exposure above the median length of time (37.4 years, RR = 2.4, 95% Cl = 1.0-5.8). A significant negative association was observed for previous tubal ligation (RR = 0.2, 95% Cl = 0.03-0.9). A history of several gynecologic and abdominal oper ations, given by responses to the questionnaire, was ex amined to determine if exposure to talc from surgeon's gloves increased risk [13]. No statistically significant re lationships were detected but, with the exception of ovar ian biopsies, relative risk estimates were generally below 1. An attempt was made to combine information from the questionnaire and medical records, with no important changes in the relative risk estimates. Moderately elevated relative risk estimates, which were not statistically significant, were observed with use of con doms, diaphragms (when powder was used), and genital bath talc. The level of association observed with exposure to talc on sanitary napkins (RR = 4.8, 95% Cl = 1.3 18.0) was significantly greater than unity. Respiratory Fiber Exposure Numerous sources of respiratory fiber exposure were evaluated (Table 4): the only such source showing an important effect was occupational fiber exposure in rel atives (RR = 2.8, 95% Cl = 0.9-8.8). This relative risk estimate was calculated after three cases who were both exposed to asbestos themselves and received asbestos ex posure from their relatives were excluded. DISCUSSION Genital talc exposure has been proposed as an etiologic agent of ovarian cancer [14] because talc was observed more frequently in cancerous ovaries [15] than in non cancerous ovaries, occupational studies of talc-containing asbestos showed an increased risk of lung cancer [16], asbestos has been observed in cosmetic face powders [17 19], and papillary growth has been observed after im plantation of asbestos [20] and talc [21] into the peritoneal cavity. : We found an increased relative risk (4.8) for talc use ^ on sanitary napkins with a smaller effect for genital bath ^ talc exposure (RR = 1.7). This is in accordance with the | original finding of a significant increased risk for perineal ^ talc exposure (RR = 1.9, 95% Cl = 1.3-2.9) by Cramer ^ et al. [4]. Preliminary findings from a Chinese study also = suggest that perineal application of talc-containing dusting powder increased the risk of epithelial ovarian cancer (RR 13 = 3.9, 95% Cl = 1.1-13.8) [5], A nonsignificant effect for genital talc exposure (on genitals, sanitary napkins, % or underwear) was detected in the study of Hartge et al. g [6] (RR = 2.5, 95% Cl = 0.7-10.0). Whittemore et al. 1 | [7] detected an increased risk (RR = 1.4, P = 0.06) for g. perineal exposure. In a study of borderline ovarian tu- 1 mors, an increased risk was also observed with talc ex- g- posure from use on sanitary napkins (RR = 1.9, 95% g Cl = 0.9-6.9, 8). ` | We also investigated the relationship with cumulative; | duration of all forms of genital fiber exposure (with the o time since tubal ligation subtracted). The positive asso- =f ciation (RR = 2.35) in our study for exposure longer 2: than the median length of time contrasts with the lack o f g association with duration observed by Whittemore et al. - [7], Whittemore et al. [7], however, did observe a positive dose-response relationship with frequency of exposure ^ (1-20 times per month, RR = 1.3, 95% Cl = 0.8-2.0; o >20 times per month, RR = 1.4. 95% Cl = 0.9-2.2). ^ Although Booth et al., [9] did not observe a significant (P - 0.05) trend of increasing risk with more frequent ^ use, weekly genital talc use (RR = 2.0, 95% Cl = 1 .3 - 5 " 3.4) was associated with an increased risk of ovarian i cancer. EL The results of our study and others suggest that genital "g fiber exposure may be associated with an adverse effect-< [4-8] but further study is needed to determine if this relationship is causal innature. 3 The present study also showed a significant negative^ association with tubal ligation (RR = 0.15). Harlow [22j_^ (RR = 0.3, 95% Cl = 0.3-1.1). Booth et al. [9] ( R R | = 0.2, 95% Cl = 0.1-0.6), Mori et al. [23] (RR = 0.4^ | 95% Cl = 0.2-1.0), Whittemore et al. [7] (RR = 0 .6 ,^ P = 0.07). and Irwin et al. [24] (RR = 0.7, 95% Cl -- 0.5-1.0) also observed negative associations. Although co the findings of our study differ from the positive associ- o ation observed by Koch et al. [25] the comparison rates5 [26] used in Koch's cohort study may have b een ^ underestimated. sr Tubal ligation mayprotectagainst ovarian cancer by s inhibiting the carcinogenic action of talc through blockage jp S IS E .... -^iSCCiilii;:wi&rV.iw:* The material on this page was copied from the collection of the National Library of Medicine by a third party and may be protected by U S Copyright law FIBERS AND OVARIAN CANCER 23 TABLE 3 Number and Frequency Distribution of Cases and Controls with Odds Ratios for Genital Fiber Exposure and Other Related Variables Exposure interval Attribute Cases Controls ------------------------------------------------- N % N % Odds ratio 9591 confidence ' interval Genital fiber use Yes 67 87.0 40 88.0 1.0 No 10 13.0 5 11.1 Missing 0 1 Length of use of genital fi- S37.4 39 55.7 16 39.0 2.4 ber" (years) <37.4 31 44.3 25 61.0 Missing 7 s (Median of cases and Median 41.9 24.0 controls) Ovarian biopsies Yes 6 7.8 3 6.5 1.1 No 71 92.2 43 93.5 Unilateral oophorectomy Yes 8 10.4 5 10.9 0.8 No 69 89.6 41 89.1 Tubal ligation Yes 4 5.2 6 13.0 0.2 No 73 94.8 40 87.0 Hysterectomy Yes 19 24.7 12 26.1 0.7 No 58 75.3 34 73.9 Condom use Yes 35 49.3 22 51.2 1.6 No 37 50.7 21 48.8 Missing 5 3 Diaphragm use with Yes 14 18.9 5 11.4 3.0 powder No 60 81.1 39 88.6 Missing 3 2 Genital bath talc Yes 22 28.9 8 18.6 1.7 No 54 71.0 35 81.4 Missing 1 3 Sanitary napkin with talc Yes 21 30.0 6 13.6 4.8 exposure No Missing 49 70.0 38 86.4 7 O 0 .2 - 4 .O'1 1.0-5. S' 0.3-4.4 0.2-2.5J 0.3-0.9" " 0 .3 - 1 .7J 0.6-3.9*"' 0.8-10.8" 0.7-3.9 1.3-17.8' " After subtraction of the time since tubal ligation, for those who had ligation. b Adjusted for number of live births. r Adjusted for religion. * Adjusted for years of education on subject. ' Adjusted for highest weight 20 years prior to diagnosis. 1 Adjusted for highest weight 1 year prior to diagnosis. of the fallopian tube or through a "screening" effect [27], The effects of antecedent tubal ligation should be eval uated in future studies of ovarian cancer to determine if a negative association is consistently observed and to de termine the reason for this. Several cohort studies of women with respiratory ex posure to asbestos detected an increased relative risk for ovarian cancer [1-3]. We elicited information about em ployment by relatives in occupations with asbestos or fi berglass exposure [28] and the relative risk was found to be elevated (RR = 2.8). In a previous case-control study of ovarian cancer, the relative risk for occupational as bestos exposure in relatives was not elevated [29], al th o u g h th e a u th o r s did n o t d e s c r ib e h o w th e a s b e s to s exposure was ascertained. Our initially suggestive findings regarding asbestos or fiberglass exposure in relatives should be evaluated further in additional studies. In summary, our study shows that the development of ovarian cancer may be associated with genital fiber ex-, posure (especially talc on sanitary napkins) and occupa tional exposure to fibers in relatives. Given its small sam ple size and the potential selection bias stemming from inclusion of patients from only one hospital, further re^. search needs to be performed in order to confirm our findings. * APPENDIX 1 Questions Asked to Ascertain Fiber Exposures Genital Fiber Exposure 1. H av e y ou h ad any o f th e follo w in g o p e ra tio n s to your hospitalization i n _____? --Biopsy or removal of part of an ovary -- Removal of one ovary -- Removal of uterus (hysterectomy) p rio r The material on this page was copied from the collection of the National Library of Medicine by a third party and may be protected by U S Copyright law 24 ROSENBLATT, SZKLO, AND ROSENSHEIN TABLE 4 Number and Frequency Distribution of Cases and Controls with Odds Ratios for Selected Characteristics Related ____ ________________ __ to Respiratory Fiber Exposure Exposure interval Respiratory fiber exposure Cosmetic face powder use Insulation installed at residence Living in the vicinity of a fiber-emitting industrial establishment Applied bath talc to body (respiratory exposure) Fiber exposure in relatives Use of spackling and taping compounds Attribute Yes No Yes No Missing Yes No Missing Yes No Missing Yes No Missing Yes No Yes No Missing Cases N % 69 89.6 8 10.4 38 50.7 37 49.3 2 30 39.5 46 60.5 1 7 9.2 69 90.8 1 47 61.8 29 38.2 1 18" 24.3 56 75.7 20 29.0 49 71.0 8 Controls N % 41 89.1 5 10.4 24 54.5 20 45.4 2 17 37.8 28 62.2 1 4 8.9 41 91.1 1 24 55.8 19 44.2 3 5 10.9 41 89.1 14 31.1 31 68.9 1 * Adjusted for highest weight 1 year prior to diagnosis. * Adjusted for years of education on subject. ' Adjusted for number of live births. eexxpo^seddemto "hb^ers.WFFiLberreeixUpr iossdure included as^bestos',* 't*alc, or fibeerXgfl>assSeedxp,0osfuirbeerS and had a househo,d ' Adjusted for religion. Odds ratio 1.3 1.1 95% coni inter* 0.3-3.1 0.4-2.' 1.2 0.3-4,( 1.0 0.3-3,< 1.6 0,6-2.: 2.8 0.9-8 1.6 0.5-3. S 3 ` . who had been occuVpati --Tubal ligation -- Any other abdominal operation (These items were confirmed by examination of medical records) 2. Did^you use a diaphragm prior to your hospitalization If yes: Did you use a powder to dust and dry the diaphragm? If yes: Was it talc? 3. Did you and your sexual partner ever use a condom prior to your hospitalization i n ____ ? 4. Have you regularly applied talcum powder to your body after bathing or for other reasons prior to your hospitalization i n ____ ? Did you commonly apply the talcum powder to your genital area? 5. Have you used talc on sanitary napkins or any other sanitary products used during your menstrual period prior to your hospitalization i n ____ ? Respiratory Fiber Exposure 1. Prior to your hospitalization i n _____had you ever regularly used cosmetic face powder? 2. Have you ever had insulation installed in a place that you lived in prior to your hospitalization i n _____? 3. Have you ever lived in the vicinity of a shipyarc asbestos or talc mine, or an asbestos, talc, or fiber) processing plant prior to your hospitalization i n __ i 4. Have you regularly applied talcum powder to > body after bathing or for other reasons prior to ^ hospitalization i n _____? f Did you commonly apply the talcum powder to i face, upper torso, or legs and feet? * 5. Have you or anyone who has ever lived in | household (including your husband) been employer any of the following industries prior to your hospi zation i n ____ ? (a) Installation or removal of insulation materia (b) Brake lining manufacture ' (c) Automobile repair involving brake repair (d) Roofing using asbestos materials (e) Asbestos milling or mining (f) Asbestos textile or paper manufacture (g) Building construction (h) Other industries where asbestos is used i (i) Talc mining and milling (j) Other industries where talc is used (k) Fiberglass or mineral wool manufacture (l) Other industries where fiberglass or mineral wool was used FIBERS AND OVARIAN CANCER 25 6. Did you ever use spackling and taping compounds? If the respondent answered yes to any of these ques tions, they were asked when the exposure started and stopped. If they could not answer this question, they were asked how long the exposure occurred. 13. Tolbert, T. W ,, and Brown, J. L Surface powders on surgi gloves. Arch. Surg. 115, 729-732 (1980). 14. Longo, D. L., and Young, R. C. Cosmetic talc and ovarian cancel -- Lancet 2, 349-351 (1979). ft) 15. Henderson, W. 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