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FILE NAME Talc TALC DATE 1992 DOC TALC029 DOCUMENT DESCRIPTION Journal Article - Mineral Fiber Exposure and the Development of Ovarian Cancer GYNECOLOGIC ONCOLOGY 45 20-25 1992 Mineral Fiber Exposure and the Development of Ovarian Cancer o The KARIN A. ROSENBLATT PH.D MOYSES SZKLO M.D. DR.P.H NEIL B. ROSENSHEIN M.D. * material Department of Epidemiology The Johns Hopkins School of Hygiene and Public Health Baltimore Maryland 21218 and + Gynecology and Obstetrics The Johns Hopkins Hospital Baltimore 21218 Department of Maryland on Received July 10 1991 this A hospital 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 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 CI = 1.2917.79 genital fiber exposure from different sources for a long cumulative exposure 37.y4ears length of time OR = 2.35 95 CI = 0.95 5.8a0nd occupational fiber exposure in relatives OR = 2.81 95 CI = 0.90 8.7A 5 negative association was observed for antecedent tubal ligation OR = 0.15 95 CI = 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 13 Similarly containing substances such as talc have also been implicated as risk factors 4-9 A matched control study of epithelial ovarian cancer was conducted 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 University of Illinois at Champaign 120 Huff Hall 1206 S. Fourth St. Champaign IL 61820 Correspondence to Dr. Rosenblatt at this address page eligibility criteria were ascertained from the Johns Hop- : . was kins Hospital One hundred eight 77.1 of these cases were successfully interviewed These cases were diag- copied nosed within 6 months of admission were pathologically confirmed by examination of the ovaries were admitted - as patients for treatment or diagnosis and were resi- from dents of the United States Controls were patient fe- the males without gynecologic or malignant conditions who colection 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 of the matching criteria a control could not be found for all + the cases teriori and 1 National within Unmatched cases were therefore matched a pos-= to controls to form matched triplets of 2 cases control A posteriori matching was performed ; the same year interval by race and by closest Library date of diagnostic admission The matching procedure ~ allowed for the inclusion of 77 cases in the study There of 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 Medicne by METHODS a third Data were ascertained primarily from a questionnaire ~ party that was administered to participants both by telephone | and and in the hospital Information on previous abdominal - and gynecologic operations was also ascertained from . medical records may The questionnaire elicited information on the presence ; be and length of genital fiber and respiratory fiber exposure | protected reproductive factors estrogen use family history of can- * cer in degree relatives and other contraceptive use Descriptions of the questions used to ascertain fiber ex- by posure are listed in Appendix 1. Fiber exposure was de- US US fined as exposure to asbestos talc which may contain Copyright asbestos and fiberglass An attempt was made to estimate the overall effect of 20 0090-8258 1.50 Copyright '1992 by Academic Press Inc. All rights of reproduction in any form reserved law . FIBERS AND OVARIAN CANCER 21 dose or length of genital and respiratory fiber exposure This was accomplished by adding the number of years of each type of genital or respiratory exposure from all sources Since many of these exposures occurred at the same time these variables should be considered as crude measures of dose rather than the true length of exposure Conditional logistic regression 10 was used to determine the strength of the association Odds ratios were calculated to describe the relationship of genital and respiratory fiber exposure to ovarian cancer The odds ratio is an estimate of the relative risk for relatively rare dis- eases such as ovarian cancer and in this paper is referred to as the relative risk estimate RR The following variables were assessed as potential confounders Tobacco use Number of cigarettes per day Ovulatory time period Number of pregnancies Cancer in mother or father Obesity 1 year prior to diagnosis Obesity 20 years prior to diagnosis Obesity at highest weight during the 20 years prior to diagnosis Obesity according to average weight during the 20 years prior to diagnosis Husband's and subject's education Previous cancer Marital status Religion Use of oral contraceptives Use of contraceptive foams creams and jellies by themselves Use of an IUD On the basis of the strength of their relative risk estimates and the difference in frequency with which they were observed in cases and controls the following variables were identified as potential confounders measures of obesity socioeconomic status subject's education RR = 0.5 95 CI = 0.2-1.1 and religion Jewish RR 2.9 95 CI = 0.6-13.8 Catholic RR = 0.5 95 CI = 0.2-1.5 reproductive status total live births 1-2 RR = 0.7 95 CI = 0.2-1.9 live births > RR = 0.4 95 CI = 0.2-1.3 and oral contraceptive use OR = 0.9 95 CI = 0.3-23.0 Obesity 1 year prior to diagnosis RR = 2.3 95 CI = 0.9-6.1 obesity 20 years prior to diagnosis RR = 2.1 95 CI = 0.7-6.9 and obesity according to highest weight during the 20 years prior to diagnosis RR = 1.5 95 CI = 0.7-3.2 were also found to be potential confounders Obesity was defined as a weight index greater than that exhibited by women in the 85th percentile 11 of the population TABLE 1 Distribution of Matched Cases and Controls Cases Controls N % N % The The Age years material Less than 30 311235 30-39 31 235 40-49 311235 3.9 1.3 14.3 21822 4.4 material 2182 material 21822 17.4 50-59 311235 27.3 21822 21.7 60-69 311235 45.4 21822 this 70-79 311235 6.5 3 page 80 or higher - 1.3 - 2.2 Total Race White Black Total 77 46 was was - copied 27F 90.9 41 89.1 copied 10.S 27F 9.1 5 10.S 77 45 from "the If a potential confounder changed the relative risk es col ection timate associated with a fiber exposure by more than %colection it was retained in the multivariate model Confoundercolection depend of were sequentially added to multivariate models of the rati ing on the level with which they changed the odds of a fiber related exposure ththe e : National Interaction between fiber exposures and potential conNational founders was evaluated by comparing the deviance o models with and without the interaction term 12 Library RESULTS of Medicine Age and Racial Distribution ke Table 1 lists the age and racial distribution of cases an controls Most cases and controls were in the age group a 40 to 69. It was difficult to obtain controls that did nc third expecte have a chronic disease resultingin a lower than number of controls and Diagnoses of Controls themaiy Controls were selected so that they did not have be Tabl primary diagnostic condition for more than 1 year 2 lists the the study primary diagnosis of the controls included protectedprotecprtoteecdted Genital Fiber Exposure ty 2by es Different sources of genital fiber exposure were amined Table 3 Exposure from any of the Copyright potentia sources of genital fiber was highly prevalent 91.1 Copyright controls and not found to be related to ovarian canceCopyright RR= 1.0 95 CI = 0.2-4.0 Since it was felt thalalwaw this index did not accurately characterize cumulative ex posure the median length of exposure from all genita sources with the time since tubal ligation subtracted was 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 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 CI = 1.0-5.8 A significant negative association was observed for previous tubal ligation RR = 0.2 95 CI = 0.03-0.9 A history of several gynecologic and abdominal operations given by responses to the questionnaire was examined to determine if exposure to talc from surgeon's gloves increased risk 13 No statistically significant relationships were detected but with the exception of ovarian 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 condoms 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 CI = 1.318.0 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 relatives RR = 2.8 95 CI = 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 noncancerous ovaries occupational studies of 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 tale 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 The talc exposure RR = 1.7 This is in accordance with the material original finding of a significant increased risk for perineal talc exposure RR = 1.9 95 CI = 1.3-2.9 by Cramer et al 4 Preliminary findings from a Chinese study also on suggest that perineal application of containing dusting this page powder increased the risk of epithelial ovarian cancer RR = 3.9 95 CI = 1.1-13.8 5 A nonsignificant effect for genital talc exposure on genitals sanitary napkins was or underwear was detected in the study of Hartge et al copied 6 RR = 2.5 95 CI = 0.7-10.0 Whittemore et al 7 detected an increased risk RR = 1.4 P = 0.06 for from perineal exposure In a study of borderline ovarian tu- mors an increased risk was also observed with talc ex- the posure from use on sanitary napkins RR = 1.9 95 cumulaticovleection CI= 0.9-6.9 8 We also investigated the relationship with duration of all forms of genital fiber exposure with the of = time since tubal ligation subtracted The positive asso- the ciation RR 2.35 in our study for exposure longer National than the median length of time contrasts with the lack of association with duration observed by Whittemore et al Library 7 Whittemore et al 7 however did observe a positive response relationship with frequency of exposure 1-20 times per month RR = 1.3 95 CI = 0.8-2.0 of 20 times per month RR = 1.4 95 CI - 0.9-2.2 Although Booth et al 9 did not observe a significant P= 0.05 trend of increasing risk with more frequent Medicne use weekly genital talc use RR= 2.0 3.4 was associated with an increased cancer 95 risk = CI 1.3 by a of ovarian third The results of our study and others suggest that genitalgenital party party fiber exposure may be associated with an adverse effect party 4-8 but further study is needed to determine if this and may relationshipis causal in nature negative The present study also showed a significant association with tubal ligation RR= 0.15 Harlow 22 protected = protected = 0.3 95 CI 0.3-1.1 Booth et al 9 RR RR = = protected = 0.2 95 CI 0.1-0.6 Mori et al 23 RR 0.4 protected 95 CI= 0.2-1.0 Whittemore et al 7 RR= 0.6 P = 0.07 and Irwin et al 24 RR= 0.7 95 CI by 0.5-1.0 also observed negative associations Although the findings of our study differ from the positive associ- Copyright Copyright ation observed by Koch et al 25 the comparison rateCsopyright 26 used in Koch's cohort study may have been protect underestimated Tubal ligation may l| aw law against ovarian cancer by inhibiting the carcinogenic action of talc through blockage 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 S UEEEEEEEEEEEEEEEEET N / Controls os N % Genital fiber use Length of use of genital fiber years Median of cases and controls Ovarian biopsies Unilateral oophorectomy Tubal ligation Hysterectomy Condom use Diaphragm use with powder Genital bath talc Sanitary napkin with talc exposure Yes No Missing 37.4 37.4 Missing Median Yes No Yes No Yes No Yes No Yes No Missing Yes No Missing Yes No Missing Yes No Missing 67 87.0 40 10 13.0 5 0 1 39 55.7 16 31 44.3 25 7 5 41.9 6 7.8 3 71 92.2 43 8 10.4 5 69 89.6 41 4 5.2 6 73 94.8 40 19 24.7 12 58 75.3 34 35 49.3 22 37 50.7 21 5 3 14 18.9 5 60 81.1 39 3 2 22 28.9 8 54 71.0 35 1 : 21 30.0 6 49 70.0 38 7 2 a After subtraction of the time since tubal ligation for those b Adjusted for number of live births -- Adjusted for religion d Adjusted for years of education on subject * Adjusted for highest weight 20 years prior to diagnosis Adjusted for highest weight 1 year prior to diagnosis who had ligation 88.0 11.1 39.0 61.0 24.0 6.5 93.5 10.9 89.1 13.0 87.6 26.1 73.9 51.2 48.8 11.4 88.6 18.6 81.4 13.6 86.4 Odds ratio 1.0 2.4 1.1 0.8 0.2 0.7 1.6 3.0 1.7 4.8 ; * 95 confidence interval The 0.2-4.0 material 1.0-5.8 on this page 0.3-4.4 was : 0.2-2.5 . copied 0.3-0.94 from 0.3-1.74 * the 0.6-3.9 . * col ection 0.8-10.874 of : the x 0.7-3.9 - National 1.3-17.8 Library of Medicne by a third 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 control study of ovarian cancer the relative risk for occupational as- bestos exposure in relatives though the authors did not was not describe elevated how the 29 al- asbestos 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-party posure especially talc on sanitary napkins and occupa- and may 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- be search needs to be performed in order to confirm our findings protected by APPENDIX 1 U S. Questions Asked to Ascertain Fiber Exposures Copyright Genital Fiber Exposure 1. Have you had any of the following operations prior law to your hospitalization in ? . -Biopsy or removal of part of an ovary -Removal of one ovary -Removal of uterus hysterectomy 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 Attribute Cases N % Controls N % Odds ratio 95 confi interv The Respiratory fiber exposure Cosmetic face powder use Yes No Yes No 69 89.6 41 89.1 1.3 ww 10.4 3222EX 10.4 54.5 ww 50.7 3222EX 1.1 ww 49.3 3222EX 45.4 Insulation installed at residence Missing ~ 3222EX Yes w 39.5 3222EX 37.8 1.2 No * 60.5 3222EX 62.2 Missing 1 1 Living in the vicinity of a fi- Yes 7 9.2 4 8.9 1.0 90.8 emitting industrial No 69 41 91.1 establishment Missing 1 1 Applied bath talc to body respiratory exposure Fiber exposure in relatives Yes 47 61.8 24 55.8 1.6 No Missing 29 38.2 19 44.2 1 3 Yes 18 24.3 5 10.9 2.8 Missing No Use of spackling and taping Yes compounds No 56 75.7 41 89.1 20 29.0 14 31.1 1.6 49 71.0 31 68.9 8 1 * 0.3-3.1 material material 0.4-2 on this this 0.3-4 page was 0.3-3,4 was copied copied 0.6-2.1 from from the 0.9-8 . the collection 0.5-3.4 colection collection of Adjusted for highest weight 1 year prior to diagnosis b Adjusted for years of education on subject Adjusted for number of live births the National National d Three cases were excluded because they had been directly exposed to fibers and had a household household National ex. posed to fibers Fiber exposure included asbestos talc or fiberglass exposure occupati member who had been National National Adjusted for religion Library -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 in ? 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 in ? 4. Have you regularly applied talcum powder to your body after bathing or for other reasons prior to your hospitalization in ? 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 in ? Respiratory Fiber Exposure 1. Prior to your hospitalization in had you ever of 3. Have you ever lived in the vicinity of a shipyard Medicine asbestos or talc mine or an asbestos talc or fiber~flMedicine processing plant prior to your hospitalization in __2 Medicine 4. Have you regularly applied talcum powder to by body after bathing or for other reasons prior to third hospitalization in ? i third party Did you commonly apply the talcum powder to4 party face upper torso or legs and feet 5. Have you or anyone who has ever lived in 3 and may household including your husband been employe any of the following industries prior to your hospi zation in ? be : protec d materia a Installation or removal of insulation b Brake lining manufacture c Automobile repair involving brake repair d Roofing using asbestos materials by U e Asbestos milling or mining S. f Asbestos textile or paper manufacture Copyright g Building construction h Other industries where asbestos is used i Talc mining and milling law j Other industries where talc is used regularly used cosmetic face powder 2. Have you ever had insulation installed in a place that you lived in prior to your hospitalization in ? k Fiberglass or mineral wool manufacture 1 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 questions they were asked when the exposure started and stopped If they could not answer this question they were asked how long the exposure occurred REFERENCES 1. Acheson E. D. Gardner M. J. Pipparh E. C. and Grime L. P. 1982 Mortality of two groups of women who manufactured gas masks from chrysotile and crocidolite asbestos A 40 J. Ind Med 29 344-348 year follow Br 2. Newhouse M. L. Berry G. Wagner J. C. and Turok M. E. A study of the mortality of female asbestos workers Br J. Ind Med 29 134-141 1972 3. Wignall B. K. and Fox A. J. Mortality of female gas mask assemblers Br J. Ind Med 39 34-38 1982 4. Cramer D. W. Welch W. R. Scully R. 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Sur- party vival trends in women with epithelial cancer of the ovary in Northern and Alberta 1960-1979 Clin Invest Med 5 121 124 1982 may 27. Weiss N. S. and Harlow B. L. Why does hysterectomy without bilateral oophorectomy influence the subsequent incidence of ovar- ian cancer Am J. Epidemiol 124 856-858 1986 be protected 28. Kusnetz S. and Hutchison B. K. A guide to the relatedness_ of disease USDHEW NIOSH Cincinnatti OH 1979 29. Newhouse M. Pearson M. Fullerton J. M. : Boesen E. A. M. and Shannon H. S. A control study of carcinoma by by U.S. of the ovary Br J. Prev Soc Med 31 148 1531977 Copyright law