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FILE NAME Talc TALC DATE 2014 DOC TALC134 DOCUMENT DESCRIPTION Journal Article - Talc Use and Ovarian Cancer- Epidemiology Between a Rock and a Hard Place DOI dju260 First published online September 11 2014 xs Published by Oxford University Press 2014 This work is written by a US Government employee and is in the public domain in the US Talc Use and Ovarian Cancer Epidemiology Between a Rock and a Hard Place Nicolas Wentzensen Sholom Wacholder Correspondence to Nicolas Wentzensen MD PhD MS Division of Cancer Epidemiology and Genetics National Cancer Drive Room E114 Bethesda MD 20892-9774 mail Institute 9609 Medical Center wentzenn@mail.nih.gov With over 14000 deaths in the United Stated each year ovarian cancer is the most lethal gynecologic cancer 1 Most ovarian can- cers are detected at late stage and have poor prognoses Given the failure at prevention of death by screening for ovarian cancer using CA and transvaginal ultrasound 2 finding potential preventive interventions has greatest promise of reducing ovarian cancer mortality Ample epidemiologic evidence suggesting that inflammation plays an important role in ovarian carcinogenesis include associa- Downlade tions of incessant ovulation endometriosis and pelvic inflamma- tory disease with increased ovarian cancer risk 3 and reduced risks from observed for regular aspirin users 4 Evidence on perineal talc use as a risk factor for ovarian can- cer is more equivocal Talc a metamorphic mineral composed of magnesium silicate that absorbs water is a common component of genital powders Naturally talc has similarities to and occurs with asbestos although early studies hypothesized that asbestos contamination of talc may have a causal role in ovarian carcinogen- htp:/jnci.oxfrdualsg/ esis later control studies reporting use after cosmetic prod- in medical or pharmacy records that could be used to confirm or supplant reported use Therefore reporting bias is of great concern in control studies Previous studies have argued that a stronger association observed for certain ovarian cancer subtypes speaks against reporting bias 8 However the clinical presentation and prognosis of ovarian cancer which varies by ovarian cancer subtype may differentially affect cases reporting Further the quantification of tale dose is very difficult Cosmetic perineal powders vary in talc content Talc can be applied as spray or powder either directly to the genital region using swabs or by application on diaphragms The amount of talc applied or making contact with the ovary may vary substantially by mode of application Particularly the cohort studies suffer from very limited exposure information The Nurses Health Study which previously reported on talc use collected only information on frequency of talc use per week 11 whereas the Women's Health Initiative 7 only collected information on duration of use not on frequency So far no epidemiologic study has demonstrated a response relationship between talc use and ovarian cancer risk ucts became asbestos in the United States continued to show associations In addition to the difficulties of talc exposure assessment ovarian by guest The biological basis of possible talc cancer is a challenging outcome because of its rarity and heteroge- carcinogenicity is not neity 12 There is increasing evidence supporting the hypothesis on understood Direct physical contact of tale with ovarian epithelium that ovarian cancers may derive from different cells of origin For May may cause chronic inflammation some studies have suggested ret- example some serous ovarian cancers supposedly originate in the rograde transport of talc particles through the reproductive tract fallopian tubes while some endometrioid 29 5 A mechanism that would not require direct contact of talc with cancers may originate in 2016 the tissue at risk is reduction of ectopic or orthotopic endometrial tissue 13 Reports of a stronger MUC1 antibodies which are association of talc use with serous ovarian cancers compared with associated with lower risk of ovarian cancer 6 other subtypes 8 might suggest that talc to the fallo- In this issue of the Journal Houghton and colleagues report on exposure pian tubes plays a role in carcinogenesis However the associations the association between perineal powder use and ovarian cancer with serous cancers are not consistent and experimental data are risk from the observational arm of the Women's Health Initiative lacking Even larger sample sizes and quality subtype data are WHI 7 Although several control studies have reported needed to establish specific associations associations between talc use and ovarian cancer risk 8-10 the Based on the evidence from epidemiologic studies in 2006 the only previous prospective evaluation of talc use and ovarian can- International Agency for Research on Cancer IARC classified cer risk did not find an association with ovarian cancer overall but geni- tal talc use as possibly carcinogenic to humans carcinogen group 2B with serous ovarian cancer the most common and most lethal sub- 14 The limited evidence for this recommendation based type 11 With over 400 cases the new study was well powered to was pri- marily on the control studies that showed increased risk of ovar- confirm previously reported effect sizes 7 However the authors ian cancer From a regulatory perspective cosmetic products do not found neither an association between perineal powder use with require review by the US Food and Drug Administration FDA but ovarian cancer overall nor with specific subtypes the FDA can act on evidence of harm related to cosmetic products Assessing the association between talc use and ovarian cancer While the FDA is currently monitoring potential health effects of cos- risk poses several challenges First and foremost assessment of talc metic talc use the activities have mainly focused on assuring that cos- exposure relies purely on report Talc use is not documented metic tale products are asbestos 15 Helpful recommendations inci.oxfordjournals.org JNCI [ Editorial 1 of2 to women will need to weigh the benefits of perineal talc use against the potential harms and the effective alternative products for reducing moisture absorption to prevent chafing and rashes no evaluation of term use of alternative products has been undertaken How do the results from Houghton et al 7 change the assessment of harm related to perineal talc use Overall the evidence regarding carcinogenicity of talc use remains inconclusive While reporting bias may explain the positive associations reported from control studies the limitations of cohort studies regarding possibil- exposure assessment still do not completely eliminate the ity that talc use is associated with ovarian cancer risk So where do we go from here Ideally we would want to have quality exposure data on talc use in a cohort setting with periodic updates on exposure These data are currently not available Ovarian cancer is rare and collecting these data prospectively will take time Behavioral exposures such as cosmetic talc use are very difficult to assess even though they are important for etiology and possibly public health Cohort studies need attentive participants long follow detailed histology and large sample size to be helpful control studies must avoid differential misclassification There does not seem to be an independent more objective data source that could be used to assess talc exposure With the current evidence it does not seem likely that additional conventional epidemiological studies will strengthen the evidence for or against talc carcinogenicity Other exposures face similar challenges of misclassification and reporting bias such as diet and physical activity One possible long shot for exposure assessment might be phone apps similar to those that can improve food frequency assessment or physical activity 16 These technologies could improve quantification of talc use providing detailed data on dose frequency and duration in cohort study participants Meanwhile cosmetic talc use has substantially decreased in the United States between 1982 and 2004 17 While the reasons are not clear it is possible that consumers already react to reports of potential harms despite the lack of clear evidence References 1. American Cancer Society Cancer Facts and Figures 2012 2. Buys SS Partridge E Black A et al Effect of screening on ovarian cancer mortality the Prostate Lung Colorectal and Ovarian PLCO Cancer Screening 2295-2303 Randomized Controlled Trial JAMA 3. 3. Ness RB Cottreau C. Possible role of ovarian epithelial inflammation in ovarian cancer J Natl Cancer Inst 1459-1467 4. Trabert B Ness RB Ciganic WH et al Aspir~-nnonasp~-rinnonsteroidal inflammatory drug and acetaminophen use and risk of invasive epi- thelial ovarian cancer a pooled analysis in the Ovarian Cancer Association J Natl Consortium Cancer Inst 2014 djt431 djt431 doi djt431 djt431 5. 5. Cramer DW Welch WR Berkowitz RS Godleski JJ Presence of talc in pelvic lymph nodes of a woman with ovarian cancer and term gen-- ital exposure to cosmetic talc Obstet Gynecol 2007 Pt 498 501 6. 6. Cramer DW Ernstoff L McKolanis JR et al Conditions associ ated with antibodies against the associated antigen MUC1 and their relationship to risk for ovarian cancer Cancer Epidemiol Biomarkers Prev 1125 1131 7. 7. 8. 8. 9. 9. 10. Houghton SC Reeves K Hankinson SE et al Permeal powder use and risk J of ovarian canceNar tl Cancer Inst dju208 10.1093 Cramer DW Liberman RF Ernstoff L et al Genital talc exposure and risk of ovarian cancer IntJ Cancer .351 35.351 6356 MuscaJtEHuncharek MS Perineal talc use and ovarian cancer a critical review EurJ Cancer Prev 139 146 Terry KL Karageorgi S Shvetsov YB et al Genital powder use and risk of ovarian cancer a pooled analysis of 8,525 cases and 9,859 controls Cancer Prev Res Phila -811-821 11. 12. Gertig DM Hunter DJ Cramer DW et al Prospective study of talc use and ovarian cancer J Natl Cancer Inst 249 25 249 2 252 Yang IIP Trabert B Murphy MA et al Ovarian cancer risk factors by histologic subtypes in the AARP Diet and Health Study IntJ Cancer 2012 938-948 13. Sherman ME Guido R Wentzensen N Yang IIP Mai PL Greene MHMH New views on the pathogenesis of grade pelvic serous car- cinoma with suggestions for advancing future research Gynecol Oncol 645 650 14. IARC Working Group on the Evaluation of Carcinogenic Risks to Monographs Humans Talc Not Containing Asbestiform Fibres In IARC on the Evaluation of Carcinogenic Carcinogenic Risks to Humans Volume 93. Carbon Black Titanium Dioxide and Talc 277-412 15 FDA Talc Food and Drug Administration Homepage 2014 16. Rusin M Arsand E Hartvigsen G. Functionalities and input meth- ods for recording food intake a systematic review Int J Med Inform 2013 653-664 17. Kelly TD Matos GR Historical Statistics for Commodities in the United States April 9 2014 Mineral and Material Notes The authors report no conflict of interest Affiliation of author Division of Cancer Epidemiology and National Cancer Institute National Institutes of Health Rockville SW Genetics MD NW Downlade from htp:/jnci.oxfrdjunals.org/ htp:/jnci.oxfrdunals.og/ htp:/jnci.oxfordjournals.org/ by guest on May 29 2016 of Editorial | JNCI Vol 106 Issue 9 | dju260 | September 10 2014