Document Krjxo6azYkE60jQE9DB5960w

FILE NAME Talc TALC DATE 1992 DOC TALC030 DOCUMENT DESCRIPTION Journal Article - Perineal Exposure to Talc and Ovarian Cancer Risk yn yb ERIS ABER elie 9 Bi Us are entre camer Perineal Exposure to Talc and Ovarian Cancer Risk The 5 bots material BERNARD L. HARLOW PhD DANIEL W. CRAMER MD ScD DEBRA A. BELL MD . on AND WILLIAM R. WELCH MD Ry this ** Objective We sought to determine whether the use of talc in genital hygiene increases the risk for epithelial ovarian cancer Methods We interviewed 235 white women diagnosed with epithelial ovarian cancer between 1984-1987 at ten Boston metropolitan area hospitals and 239 population- based controls of similar race age and residence Results Overall 49 of cases and 39 of controls re- ported exposure to talc via direct application to the perineum or to undergarments sanitary napkins or diaphragms which yielded a 1.5 odds ratio OR for ovarian cancer 95 confidence interval CI 1.0-2.1 Among women with perineal exposure to talc the risk was significantly elevated in the subgroups of women who applied it 1 directly as a body powder OR 1.7 95 CI 1.1-2.7 2 on daily basis OR 1.8 95 CI 1.1-3.0 and 3 for more than 10 years OR 1.6 95 CI 1.0 2.T7he greatest ovarian cancer risk associated with perineal talc use was observed in the subgroup of women estimated to have made more than 10,000 applications during years when they were ovulating and had an intact genital tract OR 2.8 95 CI 1.4 5.4 however this exposure was found in only 14 of the women with ovarian cancer Conclusions These data support the concept that a life- time pattern of perineal talc use may increase the risk for epithelial ovarian cancer but is unlikely to be the etiology for the majority of epithelial ovarian cancers Obstet Gy- necol 19 26 The theory that human ovarian cancer may be mesotheliomas that originate from asbestos exposure was first proposed by Graham and Graham.,,Later Parmley and Woodruffsuggested that effluences that may arise from the vagina uterus or tubes might enter the pelvic cavity and interact with ovarian surface epithe- From the Obstetrics and Gynecology Epidemiology Center Brigham and Women's Hospital Harvard Medical School Boston Massachu- setts Supported by grant R01 CA 42008 from the National Cancer Institute lium to induce such mesotheliomas Longo and Youngfurther speculated that cosmetic talc might act in this manner because of its chemical similarity to asbestos Although there is little doubt that asbestos may induce mesotheliomas the link between genital exposure to talc and ovarian cancer is less clear The few epidemiologic studies that have examined the association between talc and ovarian cancer re- ported only modest elevations of risk but data on all potential sources of genital talc exposure were limit- 4-7 The purpose of this report was to present findings from a new control study of ovarian cancer conducted in the Boston metropolitan area in which we considered a variety of modes for perineal talc exposure the frequency and duration of use and various reproductive characteristics that might influence the ability of talc to enter the pelvic cavity and affect the ovaries Peg page ver was copied 21 from t the Beet colection s of frst the < National SRT Library crest of gemen Medicne Materials and Methods oD 98 by Between July 1984 and September 1987 we identified 2 a 394 women between 18-76 years of age diagnosed with gag third borderline or malignant epithelial ovarian cancer at Be party one of ten participating hospitals in the Boston metropolitan area Permission to contact each patient was obtained in advance from the physician of record An person interview was conducted with 272 69 of the 394 cases identified Thirty percent were not Bele party Meme and may be interviewed because of physician and patient re- protected fusal patient death or relocation The final sample for analysis was further restricted to the 235 white women confirmed as having an epithelial ovarian tumor based by on an independent pathology review conducted by S. two of the authors DAB and WRW Copyright Controls were selected from the Massachusetts Town Books annual publications that list residents by name age and address according to voter precincts law For each new ovarian cancer case interviewed a ran- law ObsteVtOL r8i0cNsO 1&JUGLyYn1e9c92ologyGynecology 0029-7844 19 Table 1. Influence of Any Perineal Talc ExposureExposure on Ovarian Cancer Risk by Characteristics of Study Participants Boston Metropolitan Area 1984-1987 law Copyright U.S. U.S. by protecte& d be may and t party ie. third a by Medicne of Library National gh' the on of a colection Se ee Th the SU from 9 copied was page this on material The Cases Controls All subjects Age y 50 50 Education y /12 12 Marital status Total 235 96 139 93 142 Talc exposure 114 48.5 41 42.7 73 52.5 51 54.8 63 44.4 Total 239 101 138 115 124 Talc exposure 94 39.3 28 28.0 66 47.8 48 41.7 46 37.1 Crude OR 1.5 156 156 1.7 1.4 95 CI 1.0-2.1 1.2-3.4 0.8-2.1 1.1-3.0 0.9-2.4 Never married Ever married Religion Jewish Jewish Weight lb 40 195 35 200 14 35.0 100 51.3 21 60.0 93 46.5 24 215 21 218 6 25.0 88 40.9 12 57.1 82 37.6 0.5-5.7 1.0-2.7 1.1 0.4-3.9 1.4 0.9-2.5 140 140 Use of OCs mo 3 < or never No. of born children 123 112 66 169 53 43.1 125 49 39.2 61 54.5 114 45 39.2 31 47.0 82 27 32.9 83 49.1 157 67 42.7 1.2 0.7-1.9 1.8 1.1-3.1 23 4.5 1.3 0.8-2.3 0 233 30 38.0 32 12 27.9 1.6 0.7-4.0 1 233 21 67.7 32 5 18.5 9.2 2.9-46.2 2 40 24 60.0 63 26 41.3 2.1 0.9-3.3 3 85 39 45.9 106 51 48.1 0.9 0.6-1.6 * OR = odds ratio CI = confidence interval OCs = oral contraceptives Sources of perineal talc exposure include dusting of underwear diaphragms or sanitary napkins use by partner on his perineal area use as a body powder dom number generator selected one page from the town book corresponding to the case's precinct of residence By working forward in the town book we selected the first five female subjects within 2 years of age of the case as potential controls Of these five the first subject of the same race as the case without a history of a bilateral oophorectomy was asked to par- ticipate in the study Of the 526 controls contacted 239 interviews were conducted 25 could not be reached 10 reported a history of bilateral oophorectomy and 19 declined to participate Further details of the study methods can be found elsewhere.8 The person interview focused on the following demographic and occupational history medical and reproductive histories including pregnancies hormones used and gynecologic operations dietary history cigarette smoking and hygienic practices The hygienic practices included information regarding the use of douches type of sanitary protection used and perineal exposure to talc Queried sources of perineal talc exposure included dusting of underwear sanitary napkins and diaphragms exposure via husband's use of talc and more direct exposure to the perineum as a body powder No reliable information on talc exposure during infancy with diapering could be obtained and women using talc as a body powder on areas other than the perineum were considered nonexposed For each exposure we inquired about brands used age at first use total years of use and frequency of use per month to enable us to estimate the total lifetime number of applications from all sources of exposure Differences between cases and controls in the distribution of these various exposures to talc were exam- ined both qualitatively and quantitatively The influ- ence of confounders and effect modifiers was assessed first through stratification and then using unconditional logistic regression The primary matching variable age was retained in each logistic model The X2 test for linear trend was calculated based on the change in deviance in models with and without continuous exposure variables. ,, Results Table 1 shows the proportion of cases and controls with any reported perineal talc exposure and the associated crude exposure odds ratio OR by certain demographic and reproductive subgroups Overall a 20 Harlow al Talc and Ovarian Cancer Obstetrics & Gynecology Table 2. History of Talc Exposure by Types of Application Brand of Powders Years and Frequency of Use and Era of Use Cases Controls Adjusted OR 95 CI No genital talc application Any genital talc application Type of application Only via sanitary napkins and underwear Via partner or applications to diaphragm Via dusting powder to perineum Applications of talc per month < 5-29 30 Years of talc use 10 10-29 30 Age y at first talc use 20 20-25 25 Years since last talc use Within last 6 mo Between 6 mo y 10 y or more Era of use Exclusive use after 1960 Any use before 1960 Brand of application Brand or generic baby powder Deodorizing or other scented powders 121 51.5 114 48.5 9 3.8 20 8.5 85 36.2 32 13.6 24 10.2 58 24.7 14 6.0 49 20.9 51 21.7 66 28.1 27 11.5 21 8.9 48 20.4 36 15.3 30 12.8 29 12.3 75 31.9 91 38.7 16 6.8 145 60.7 94 39.3 12 5.0 21 8.8 61 25.5 28 11.7 25 10.5 41 16.7 15 6.3 39 16.3 40 16.3 50 20.9 26 10.9 18 7.5 27 11.3 39 16.3 28 11.7 30 12.6 57 23.9 72 30.1 17 7.2 1.0 1.5 GRE GRE 1.7 328 328 1.8 626 626 626 626 626 626 2.3 1.1 1.4 1.1 1.7 1.6 1.2 1.0-2.1 0.4-2.8 0.6-2.4 1.1-2.7 0.8-2.7 0.6-2.2 1.1-3.0 0.5-2.6 1.0-2.7 1.0-2.7 1.1-2.7 0.6-2.2 0.8-3.2 1.3-4.0 0.7-1.9 0.8-2.6 0.6-2.1 1.1-2.7 1.1-2.5 0.6-2.5 = OR odds ratio CI = confidence interval * Adjusted for parity 0 1-2 > education 12 years 12 years marital status never married ever married religion Jewish Jewish use of sanitary napkins no yes douching no yes age continuous and weight 140 lb 14l0b + Includes combinations with sanitary napkins or underwear I Restricted to women older than 10 years in 1960 100 cases and 118 controls were unexposed and used as the referent group Excludes seven cases and five controls with unknown powders Seven cases and four controls reported combinations of more than one brand and were classified according to the brand used most frequently and for the longest period Specific brands mentioned by cases were Johnson and Johnson 71 generic baby powder 20 Shower to Shower four other scented 12. Specific brands mentioned by controls were Johnson and Johnson 54 generic baby powder 18 Shower to Shower three other scented powder 14 greater percentage of cases 48.5 than controls 39.3 reported any perineal exposure to talccontaining powders Subgroups of controls in which exposure to talc appeared to be more common were women older than 50 years P = .002 ever married P = .12 Jewish P = .08 and parous P = .05 Controls who reported no oral contraceptive OC use also reported greater talc use However this interaction may be explained by the older age distribution among controls who reported perineal application of talc We observed stronger associations between talc and ovarian cancer risk in the subgroups of cases and controls younger than age 50 less well educated heavier than 140 lb 5 years before diagnosis and reporting a history of one or two live births The number of live births was the only factor that produced statistically significant heterogeneity in the ORs for the talc and ovarian cancer association Age education marital status re- ligion weight and parity were considered confounders and were included as covariates in subsequent multivariate models Use of OCs did not confound the ovarian cancer association Table 2 examines the association between talc use and ovarian cancer by variables related to the specific types and kinds of applications and measures of duration including length frequency and period of use Compared with women with no genital talc exposure women exposed to talc only through use as a dusting powder on sanitary napkins or underwear had no appreciable increased risk for ovarian cancer There was also no substantial increase in risk among women exposed to talc only through a husband's use or use in the storage of diaphragms or in combination with applications to sanitary napkins or underwear The most frequent method of perineal talc exposure was use as a dusting powder directly to the perineum The material on this page was copied from the colection of the National Library of Medicne by a A third spe party and may be protecd by U.S. Copyright law VOL 80 NO 1 JULY 1992 Harlow et al Talc and Ovarian Cancer 21 law Copyright U.S. U.S. by protecd be may and party based a third Wa a by wk wha! Medicne Sa of Library et ee National B"G REthethe of of CUR col ection es ABM the 5 from % copied TR was page ee this are on material The Table 3. Estimated Total Lifetime Perineal Applications of Containing Powders in Cases and Controls Applications Total applications None 1000 1000-10,000 > 10,000 1df 1dtfest for linear trend - 2.85 P = .094 Applications excluding use after hysterectomy or tubal ligation None 1000 1000-10,000 10,000 1df 1dtfest for linear trend = 3.19 P = .077 Applications excluding use after hysterectomy or tubal ligation and use during nonovulatory months None 1000 1000-10,000 10,000 1df 1dtfest for linear trend ====== 6.15 P = .015 Cases 121 18 54 42 121 2258 2258 2258 124 24 55 32 Controls 145 19 44 31 145 19 46 29 149 23 51 16 Adjusted OR 1.0 1.3 1.5 1.8 1.0 1.4 1.5 1.7 NEGE NEGE NEGE NEGE 95 CI 0.7-2.7 0.9-2.4 1.0-3.0 0.7-2.9 0.9-2.4 1.0-3.0 0.8-2.9 0.8-2.0 1.4-5.4 Abbreviations as in Table 2 * Adjusted for parity 0 1-2 > education 12 years 12 years marital status never married ever married religion Jewish Je + wish use of sanitary napkins no yes douching no yes age continuous and weight 140 lb 14l0b Trend test based on actual applications as a continuous variable I Excludes exposures while taking oral contraceptives while pregnant or feeding or occurring after menopause There were three cases and four controls who moved from exposed to nonexposed in this category as all of the exposure occurred during oral contraceptive use pregnancies or after menopause alone or in combination with either a partner's use or use in the storage of diaphragms This exposure occurred in 85 cases 36.2 and 61 controls 25.5 P === .01 Of the application modes studied direct perineal application produced the greatest risk OR 1.7 95 confidence interval CI 1.1-2.7 We also examined the ovarian cancer association by frequency and years of use Table 2 When monthly frequency was considered as a continuous variable in the logistic model the linear test of trend was 4.06 P = .046 indicating that the risk for ovarian cancer increased significantly with increasing frequency of applications per month The categorical analysis showed that relative to users the risk was greatest in women who applied talc at least once per day When years of use was included as a continuous variable the test for linear trend was 3.32 P = .07 The categorical analysis showed that relative to users women who applied talc for more than 10 years were at 60 greater risk for ovarian cancer Likewise perineal applications of talc early in life before age 20 or applications within 6 months of diagnosis reference age for controls produced the stronger ORs To assess whether the risk of ovarian cancer with perineal exposure to talc was affected by the time when containing products were manufactured we ex- amined the association separately in women who only used talcum powder after 1960 and in women who reported any use of talcum powder before 1960 Table 2 After restricting the population to women older than age 10 in 1960 and adjusting for age parity and a number of other demographic characteristics we found that the association of talc and ovarian cancer was greater in women using talc products before 1960 P = .025 The last entry in Table 2 shows the risks by brand of powder used No subjects could recall exclusive use of starch powders Brand or generic baby powder was used most frequently and was the category associated a with statistically significant risk for ovar- ian cancer With respect to other powders four cases and three controls reported primary use of deodorizing powders and 12 cases and 14 controls reported primary use of other scented powders It should be appreciated that because the period of exposure often occurred over decades verification of brands was not possible Table 3 examines the ovarian cancer risk associated with the total number of applications to the perineum estimated by cumulating frequency and years of use for the various kinds of exposures An 80 excess risk was associated with an estimated exposure of more than 10,000 applications equivalent to daily use for 30 22 Harlow et al = Talc and Ovarian Cancer Obstetrics & Gynecology Table 4. Adjusted Odds Ratios and 95 Confidence Intervals for Ovarian Cancer Indicators of Ovulation and Tubal by Any Perineal Exposure to Talc and Occlusion Cases Controls All subjects cycle pain Total 235 Talc exposure 114 48.5 Total 239 Talc exposure 94 39.3 Adjusted OR 1.5 95 CI 1.0-2.1 No Yes Regular period 181 88 48.6 184 77 41.9 1.4 54 26 48.2 55 17 30.9 2.0 0.9-2.2 0.8-5.2 26 12 46.2 34 16 47.1 1.1 Yes PID or 209 102 48.8 205 78 38.1 1.7 ectopic pregnancy No Yes 226 113 50.0 230 92 40.0 1.6 9 1 11.1 9 2 22.2 0.1 inflammatory PID == pelvic * disease other abbreviations as in Table 2 as aSboourdcyespoowf dpeerrineal talc exposure include dusting of underwear diaphragms or sanitary napkins use by partner on his + Adjusted for parity 0 1-2 > education 12 years 12 years marital status never married Jewish use of sanitary napkins no yes douching no yes age continuous and weight 140 lb ever married 14l0b perineal religion 0.4-3.4 1.1-2.5 1.1-2.4 0.01-7.0 area use Jewish years as compared with users When considered as a continuous variable in the logistic model the linear test of trend was 2.85 P = .094 The remaining entries in Table 3 show how conditions that either close the upper genital tract or are associated with anovulation affect the dose response of number of applications on ovarian cancer risk The second entry shows the effect of censoring applications that oc- curred after tubal ligation or hysterectomy No appreciable change in the ORs or the dose response was noted The third entry shows the effect of censoring applications after hysterectomy and tubal ligation and use during presumed nonovulatory periods Excluded were exposures occurring while taking OCs while pregnant or feeding and after menopause The risk associated with fewer than 10,000 applications was not substantially altered However the risk associated with more than 10,000 applications was nearly threefold and statistically significant The X test for a linear trend of risk by number of applications as a continu- ous variable increased to 6.15 P = .015 Table 4 shows the association of talc exposure and ovarian cancer based on other clinical factors that may predict either ovulation or tubal occlusion The ORs were greater in women with a history of cycle pain or regular potential clinical predictors of ovulatory cycles An association between talc and ovarian cancer was absent in women a with history of either pelvic inflammatory disease or ectopic pregnancypotential markers of a closed genital tract However only nine cases and nine controls reported a history of pelvic inflammatory disease or ectopic pregnancy and the CI on the exposure OR was correspondingly wide Table 5 shows the relative risk for any perineal use of talc when restricted to specific histologic type and grade of ovarian tumors The greatest association was found in women diagnosed with an endometrioid tumor or borderline ovarian tumor Discussion Animal and epidemiologic studies have addressed the plausibility of an association between talc and ovarian cancer Intraperitoneal injection of talc in rodents produced papillary changes in the surface epithelium not inconsistent with the first stage in the development of surface papillary epithelial neoplasms However because the ovaries of small rodents are surrounded by Table 5. History of Talc Use by Histologic Type and Grade Histologic type Any use of talc No use of talc Adjusted OR 95 CI Controls 94 Histologic type Serous 60 Mucinous 17 Endometrioid 18 Other 19 Histologic grade Borderline 26222 Grade 1 26222 Grade 2 26222 Grade 3 26222 Undifferentiated 28 145 64 25 11 21 30 11 22 24 34 1.0 1.4 1.2 2.8 1.6 2.4 1.0 1.5 1.5 1.2 0.9-2.2 0.6-2.5 1.2-6.4 0.8-3.3 1.2-4.5 0.3-2.8 0.7-3.0 0.8-2.8 0.7-2.2 Abbreviations as in Table 2 * Adjusted for parity 0 1-2 > education 12 years 12 years marital status never married ever married religion Jewish Jewish age continuous and weight 140 lb 14l0b The material on 5 this page was copied from the PTE colection 4 of Bre the a: @ National Library of aeMedicine by ee a Ce third eS? party rae and may ageprytd be protec dap vor Heke by U.S. Copyrightlaw Copyrightlaw VOL 80 NO 1 JULY 1992 Harlow et al Talc and Ovarian Cancer 23 law a RS Copyright U.S. by oH protected be may Mone and Babs, party ee third se a by SB Medicne of Library National 6 National the be of OE,... We colection (EOSIN the from cy copied Mets was ea) page ee this ey on the material The ott Table 6. Odds Ratios With 95 Confidence Intervals of Ovarian Cancer in Relation to Reported in Previous Epidemiologic Studies Any Perineal Exposure to Talc as Cases Controls Author year Total Talc exposure Total Talc exposure Crude OR 95 CI Cramer et al 1982 Hartge et al 1983 Whittemore et al 1988 Harlow and Weiss 1989 Booth et al 1989 Harlow et al 1992 current study All studies 215 135 188 116 217 235 1106 92 42.8 67 49.6 98 52.1 49 42.2 141 65.0 114 48.5 561 50.7 215 171 539 158 434 239 1756 61 28.4 100 58.5 248 46.0 64 40.5 256 59.0 94 39.3 823 46.9 1.9 1.3-2.9 0.7 0.4-1.1 1.4 0.9-2.0 1.1 0.7-2.1 1.3 0.9-1.9 1.5 0.9-1.8 1.3 1.1-1.6 Abbreviations as in Table 2 * as wHealrltge P Hoover R Lesher LP et al Talc and ovarian cancer letter JAMA 1844 Odds ratio may include nonperineal talc exposure Restricted to borderline ovarian tumors * analysis peritoneal bursa which often becomes occluded and distended with follicular fluid after intraperitoneal injection of foreign bodies it is difficult to distinguish whether the papillary changes are the effects of for- body exposure or bursal distention It would be worthwhile to repeat the talc experiments in guinea pigs or rabbits the animals used in the original re- search of Graham and Graham.,, Is there evidence to suggest that talc can translocate from the vagina to the peritoneal cavity It is known that red cells and endometrial tissue are capable of retrograde flow from the fallopian tubes Experi- ments in rats confirmed the presence of talc in the ovaries after the introduction of a talc suspension into the vagina and cervical os In humans two studies observed the migration of inert carbon particles,,and radioactively labeled human albumin microspheres,,4 from the vagina to the fallopian tubes In addition several investigators have observed birefringent crys- tals embedded in ovarian tissue However critics have argued that these findings resulted from poorly designed studies or lack of precision in measuring particulates due to leaching of radionucleotide mark- ers from the test materials or the introduction of contaminants during tissue processing In six multiparous cynomolgus monkeys separately caged no translocation of talc was observed after 30 consecutive days of douching with a suspension of neutronactivated talc coupled with weekly injections of oxytocin However this study was not able to address the effects of term use or coitus which might facili- tate talc translocation Several epidemiologic studies have addressed the genital ovarian cancer association Table 6 Each study has consistently reported little or no association with the use of dusted diaphragms and stronger associations with direct perineal application Dose response of perineal talc exposure from all sources by frequency or years of use was not available in the studies by Hartge et al Hartge P Hoover R Lesher LP et al Talc and ovarian cancer letter JAMA 1844 Harlow and Weiss or Cramer et al.4 Whittemore et al reported no significant dose re- sponse by years or frequency of use whereas Booth et al reported a marginally significant trend with frequency of use Using the techniques of analysis in which ORs from multiple studies are weighted by their variances we calculated a statistically signifi- cant OR of 1.3 for any perineal talc exposure and ovarian cancer risk 95 CI 1.1-1.6 from the various studies We therefore conclude that there is an associ- ation albeit modest between ovarian cancer and per- ineal talc use However insufficient detail has been available to rule out a stronger association in certain subgroups of users Our study included greater detail on genital talc use including methods frequency and years of use Table 2 Talc applied as a dusting powder directly to the perineum carried a greater risk than less direct expo- sure via a partner's use or the dusting of undergarments sanitary napkins or diaphragms Current use of talc was associated with a greater ovarian cancer risk than past use Daily versus less than daily talc use and talc use for more than 10 years versus less than 10 years were associated with greater risk for ovarian cancer Most subjects reported use of baby powder We were unable to confirm a previous finding that powders with deodorizing agents were associated with particular risk Thus this study failed to answer a key issue in the ovarian cancer association whether the risk pertains to all cosmetic talcs or only to certain 24 Harlow et al = Talc and Ovarian Cancer Obstetrics & Gynecology preparations likely to be contaminated by asbestos Cralley et al and Rohl et al found considerable variation in the purity of cosmetic talcs with fiberform contents varying from less than 1 to 30 Most of these products were manufactured before 1970 and it is likely that the asbestiform content has decreased since 1976 when manufacturers instituted voluntary guidelines on asbestos contamination Our finding of a lower ovarian cancer risk in women with exclusive use of talc after 1960 may support this theory Because of the difficulty in obtaining a complete and detailed history of powders used the issue of whether risk pertains only to contaminated powders may need to be settled by animal experiments In our analysiwes first calculated all genital appli- cations of talc based upon frequency and years of use As a continuous variable in a multivariate model no significant dose response was observed between total genital applications of talc and ovarian cancer risk Because the translocation theory assumes an open genital tract we then excluded application after tubal ligation or hysterectomy but observed no appreciable change in the dose response Further restricting talc exposure to months when the women were likely to be ovulatory we observed a significant dose response such that women with an intact genital tract and more than 10,000 applications during ovulatory cycles had nearly a threefold increase in risk for ovarian cancer Some additional evidence that might support an interaction with ovulation includes stronger associations in women with regular periods and cycle pain Cramer et al suggested that talc contamination around the time of ovulation might lead to the incorporation of talc particulates into inclusion cysts that may form with ovulation Experiments on foreign tumorigenesis have shown that implantation of foreign bodies into the lumens of epithelial organs provides a favorable environment for carcinogenesis Alternatively Mostafa et al16 speculated that foreign exposure might produce cortical granulomas whose link to stromal hyperactivity and hormonally related cancers is argued in older literature We observed that the talc association was strongest in women with endometrioid or borderline ovarian tumors However an earlier study by Cramer et al reported no such variation in risk by histologic subtype It was noted that a greater proportion of women with endometrioid tumors than with other histologic types of ovarian cancer reported more than 10,000 lifetime applications of talc during ovulatory cycles while having an intact genital tract 34 versus 16 Although this may explain in part the strong talc- ovarian cancer association noted in women with en- dometrioid tumors it does not explain the strong association noted in women with borderline ovarian tumors of whom only 13 reported term talc exposure This variation in risk among histologic subtypes may reflect a chance finding or a need to examine endometrioid and borderline tumors more carefully for evidence of a foreign effect An unusual observation was the strong association between talc use and ovarian cancer in the subgroup of women with one or two pregnancies but a lower risk in women with either no children or three or more children Although chance may be the most likely explanation for this finding we wonder whether this peculiar interaction might reflect in part an effect of pregnancy on the degree of openness of the cervical os and its ability to allow translocation of vaginal particulates The parous cervix has a larger os than the nulliparous cervix and this could explain the greater risk in women with one child compared with women with no live births At the other extreme multiple pregnancies may offer other protective mechanisms such as reduced ovulation as discussed above that could outweigh this effect Clearly this is a very speculative hypothesis but one that might be tested in experimental studies ie repeating the vaginal talc experiments in nulliparous and parous mice or pri- mates Noncausal explanations are possible in any epidemiologic research We cannot rule out the possibility of differential over- or reporting of talc exposure in our cases and controls especially in those with reproductive events that enhance ORs In addition though we were successful in interviewing 69 of eligible ovarian cancer cases and 81 of eligible controls con- tacted we cannot assess whether the cases and con- trols not interviewed could have selectively differed in their reproductive characteristics or in their use of containing powders Because our associations are based upon responses from participating cases and controls the validity of our results depends upon the assumption that respondents and respondents were similar with respect to talc and other relevant exposures or that the magnitude of any respondentrespondent difference was similar for cases and controls Because the interview provided the only source of exposure information we were unable to assess the likelihood of this assumption The extent of this bias however is likely to be small because the reproductive characteristics and history of talc exposure in participating cases and controls are for the most part reasonably consistent with earlier epidemiologic studies of ovarian cancer Finally in our attempt to present the most accurate ORs we madea variety of adjustments to account for the confounding influence of factors associated with both ovarian cancer risk and The material on this page was copied from the colection of the National Library of Medicne by third party and may be t protec d obve y ere U.S. Copyright law law VOL 80 NO 1 JULY 1992 Harlow et al Talc and Ovarian Cancer 25 law Yt law Ate Be Copyright ot U.S. Mie by MB SE protec d ashe! be pat may and ee ee party ean ee. third ee a by Rane Medicne ae sega i of HESLibrary Library DRE National ae the Mato of REAR TAcolection Es the from ... ae copied was page this on material The talc exposure Nevertheless we cannot rule out the presence of other unknown factors that might have influenced in part our observed associations unlikely Because the overall association between genital use of talc and ovarian cancer remains weak it is that this exposure pathway is the principal one involved in ovarian cancer etiology We have previously discussed the role of dietary and metabolic factors in a model for ovarian cancer involving gonadotropin stimulation of failing ovaries Even if an etiologic association were to pertain in the subgroups of daily users or users with more than 10,000 applications during ovulatory months we calculate that by applying these ORs to the exposure rate among cases the proportion of ovarian cancer incidence attrib- utable to this level of talc exposure is about 10 Nevertheless given the poor prognosis for ovarian cancer any potentially harmful exposures should be avoided particularly those with limited benefits For this reason we discourage the use of talc in genital hygiene particularly as a daily habit References 1. Graham J Graham R. Ovarian cancer and asbestos Environ Res 115 28 2. Parmley TH Woodruff JD The ovarian mesothelioma Am J Obstet Gynecol 234-41 3. Longo DL Young RC Cosmetic talc and ovarian cancer Lancet 349-51 4. Cramer DW Welch WR Scully RE Wojciechowski CA. Ovarian cancer and talc Cancer 372 6 5. Whittemore AS Wu ML Paffenbarger RS et al Personal and environmental characteristics related to epithelial ovarian cancer II Exposures to talcum powder tobacco alcohol and coffee Am J Epidemiol 1228 40 6. Harlow BL Weiss NS A control study of borderline ovarian tumors The influence of perineal exposure to talc Am J Epide- miol 390 4 7. Booth M Beral V Smith P. Risk factors for ovarian cancer A control study BrJ Cancer 592 8 cancer 8. Cramer DW Harlow BL Willett WC et al Galactose consumption and metabolism in relation to the risk of ovarian Lancet 66 71 9. Breslow NE Day NE Statistical methods in cancer research Vol publication 1. 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Mostafa SAM Bargeron CB Flower RW Rosenshein NB Parm- ley TH Woodruff JD Foreign body granulomas in normal ova- ries Obstet Gynecol 701 2 17. Griffiths K Henderson WJ Chandler JA Joslin CAF Ovarian cancer Some new analytical approaches Postgrad Med J 1973 69-72 18. Wehner AP Hall AS Weller RE Lepel EA Schirmer RE Do particles translocate from the vagina to the oviducts and beyond Food Chem Toxicol 367-72 19. Greenland S. Quantitative methods in the review of epidemio- logic literature Epidemiol Rev 1 30 20. Cralley LJ Key MM Groth DH Lainhart WS Ligo RM Fibrous and mineral content of cosmetic talcum products Am Ind Hyg Assoc J 350-4 21. Rohl AN Langer AM Selikoff IJ et al Consumer talcums and powders Mineral and chemical characterization J Toxicol Environ Health 255-84 22. Brand KG Johnson KH Buoen LC Foreign body tumorigenesis Crit Rev Toxicol 353-94 23. 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