Research Article Cancer

Epidemiology,
Biomarkers
& Prevention
Association between Body Powder Use and
Ovarian Cancer: The African American Cancer
Epidemiology Study (AACES)
Joellen M. Schildkraut1, Sarah E. Abbott1, Anthony J. Alberg2, Elisa V. Bandera3,
Jill S. Barnholtz-Sloan4, Melissa L. Bondy5, Michele L. Cote6, Ellen Funkhouser7,
Lauren C. Peres1, Edward S. Peters8, Ann G. Schwartz6, Paul Terry9,
Sydnee Crankshaw10, Fabian Camacho1, Frances Wang10, and Patricia G. Moorman10,11

Abstract
Background: Epidemiologic studies indicate increased ovar- Results: Powder use was common (62.8% of cases and 52.9%

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ian cancer risk among women who use genital powder, but of controls). Genital powder was associated with an increased
this has not been thoroughly investigated in African Amer- risk of EOC (OR ¼ 1.44; 95% CI, 1.11–1.86) and a dose–
ican (AA) women, a group with a high prevalence of use. We response relationship was found for duration of use and
evaluate the relationship between use of genital powder and number of lifetime applications (P < 0.05). Nongenital use
nongenital powder in invasive epithelial ovarian cancer was also associated with EOC risk, particularly among non-
(EOC). serous EOC cases (OR ¼ 2.28; 95% CI, 1.39–3.74). An asso-
Methods: Subjects are 584 cases and 745 controls enrolled in ciation between powder use and upper respiratory conditions
the African American Cancer Epidemiology Study (AACES), an suggests an enhanced inflammatory response may explain the
ongoing, population-based case–control study of EOC in AA association between body powder and EOC.
women in 11 geographic locations in the United States. AA Conclusions: In a study of AA women, body powder use was
controls were frequency matched to cases on residence and significantly associated with EOC risk.
age. Logistic regression was used to calculate ORs and 95% Impact: The results support that body powder is a modifiable
confidence intervals (CI) for associations between genital and risk factor for EOC among AA women. Cancer Epidemiol Biomarkers
nongenital powder exposure and EOC risk, controlling for Prev; 25(10); 1411–7. 2016 AACR.
potential confounders. See related commentary by Trabert, p. 1369

Introduction Research on Cancer (IARC) classified perineal (genital) use of

nonasbestos–containing, talc-based body powder as "possi-
Genital powder use may be a modifiable risk factor for
bly" carcinogenic to humans (2). Although particles of asbes-
epithelial ovarian cancer (EOC), the most deadly of all gyne-
tos have been found in older body powder formulations,
cologic cancers (1). In 2010, the International Agency for
particularly prior to 1976 (3), more recent body powder
formulations no longer contain asbestos (4, 5). However,
1
the relationship between genital powder use and ovarian
Department of Public Health Sciences, University of Virginia, Char- cancer appears to persist (6). It has been proposed that
lottesville,Virginia. 2Hollings Cancer Center and Department of Public
Health Sciences, Medical University of South Carolina, Charleston, talc-containing powders may promote cancer development
South Carolina. 3Population Science Division, Rutgers Cancer Institute through local inflammation, increased rates of cell division
of New Jersey, New Brunswick, New Jersey. 4Case Comprehensive and DNA repair, increased oxidative stress, and increased
Cancer Center, Case Western Reserve University School of Medicine,
Cleveland, Ohio. 5Cancer Prevention and Population Sciences Pro- cytokine levels (7).
gram, Baylor College of Medicine, Houston, Texas. 6Department of A recent pooled analysis of eight population-based case–
Oncology and the Karmanos Cancer Institute Population Studies and control studies demonstrated an elevated OR of 1.24 for the
Disparities Research Program, Wayne State University, Detroit, Michi-
gan. 7Division of Preventive Medicine, University of Alabama at Bir- association between genital powder use and EOC (6). Some
mingham, Birmingham, Alabama. 8Epidemiology Program, Louisiana (7–15) but not all (6, 8, 16) previously published studies of talc
State University Health Sciences Center School of Public Health, New and ovarian cancer reported a dose–response relationship with
Orleans, Louisiana. 9Department of Medicine, University of Tennessee
Medical Center-Knoxville, Knoxville, Tennessee. 10Duke Cancer Insti-
genital powder use for frequency, duration, or number of
tute, Duke University Medical Center, Durham, North Carolina. applications. In addition, some studies reported a stronger
11
Department of Community and Family Medicine, Duke University association among the most common serous histologic subtype
Medical Center, Durham, North Carolina.
(4, 10, 14, 16, 17) although the pooled analysis did not confirm
Corresponding Author: Joellen M. Schildkraut, University of Virginia, PO Box this finding (6). Only one prospective study (17) found a
800765, 560 Ray C. Hunt Drive, Charlottesville, VA 22903. Phone: 434-924- significant association with ever genital talc use and invasive
8569; Fax: 434-924-8437; E-mail: jms2yf@virginia.edu
serous EOC (RR ¼ 1.40; 95% CI, 1.02–1.91), although no
doi: 10.1158/1055-9965.EPI-15-1281 overall association with EOC was found. The Women's Health
2016 American Association for Cancer Research. Initiative (WHI; ref. 18) did not detect an association with

www.aacrjournals.org 1411
 Schildkraut et al.

genital talc use and EOC. Neither prospective study found application as nongenital use only, genital use only, or genital
evidence of a dose–response relationship. and nongenital use. Lifetime number of applications was
Previous studies of genital powder use have included mostly calculated by multiplying the number of body powder applica-
white women. However, two studies reported analyses stratified tions per month by the number of months used. Occupational
by race and both found an increased EOC risk among African exposure to talc (yes, no) was available only for subjects
American (AA) women who used genital talc (14, 15). One completing the long baseline survey.
study reported a nonsignificant association between one or
more years of talc use and risk of ovarian cancer, OR ¼ 1.56, Statistical analysis
[95% confidence interval (CI), 0.80–3.04] among a small The prevalence of demographic characteristics was calculated
sample of 128 AA EOC cases and 143 AA controls, who were and t tests and c2 tests were performed to compare distributions
shown to have higher prevalence of talc use compared with between cases and controls. Because of the relatively small num-
whites (14). A second study reported an imprecise but signif- ber of women who reported having only used genital powder (43
icant association with genital talc use with an OR of 5.08 (95% cases and 44 controls), we merged this exposure category with
CI, 1.32–19.6) among a very small sample of 16 cases and 17 those who reported use of both nongenital and genital powder,
controls (15). In this article, we present analyses of the rela- creating an exposure category of "any" genital powder use.
tionship between both genital powder and nongenital powder Unconditional multivariable logistic regression was performed
exposure from the African American Cancer Epidemiology to calculate ORs and 95% CIs for the associations between body
Study (AACES), an ongoing, multicenter case–control study of powder exposure ("only" nongenital use, and "any" genital use)

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invasive EOC in AA women. and risk of EOC. Body powder exposure was further examined by
frequency of use (less than 30 times per month, daily), duration of
use categorized as less than the median or the median and greater
Materials and Methods among the controls (<20 years, 20 years), and lifetime number
Study population of applications categorized as less than the median or the median
AACES is an ongoing, population-based, case–control study of and greater among controls (<3,600, 3,600 lifetime applica-
invasive EOC in AA women in 11 locations (Alabama, Georgia, tions). Trend tests for frequency, duration, and lifetime applica-
Illinois, Louisiana, Michigan, New Jersey, North Carolina, Ohio, tions of powder use by route of exposure were conducted sepa-
South Carolina, Tennessee, and Texas). Institutional review board rately in two subsamples: only nongenital users plus never users
approval was obtained from all participating institutions. Meth- and any genital users plus never users. For each subsample, each of
ods have been described in detail elsewhere (19). Briefly, cases the above variables was entered into a logistic regression as
include AA women 20 to 79 years of age with newly diagnosed multiple indicator variables representing three levels and two
EOC. With a goal of enrolling an equal number of cases and degrees of freedom (i.e., for frequency of use: no exposure, less
controls, controls were AA women identified through random than daily, daily), adjusting for confounders. Trends were eval-
digit dialing, with at least one intact ovary and no history of uated by statistical tests for the association between frequency/
ovarian cancer, and frequency matched to cases on region of duration/lifetime applications with EOC risk, using Wald tests to
residence and 5-year age categories. Participants complete a simultaneously test the equality of parameter estimates with zero.
baseline telephone interview, which includes detailed questions Because experimental data suggest a relationship between inhaled
on demographic characteristics; reproductive, gynecologic, and inert particles and asthma (20), a logistic regression analysis was
medical history; hormone therapy (HT) and oral contraceptive conducted to determine the association between body powder
(OC) use; cancer family history and lifestyle characteristics includ- use and upper respiratory conditions (yes/no), controlling for
ing smoking, alcohol consumption, and physical activity. In an EOC case/control status.
effort to obtain information from as many women as possible, a Covariates included reference age in years (age at diagnosis
short version of the questionnaire is offered to those who would for cases and age at baseline interview for controls); study site
otherwise refuse to participate in the study. Accrual began in [Alabama, Louisiana, New Jersey, North Carolina, Ohio, South
December 2010 and as of August 31, 2015, 593 cases and 750 Carolina, Texas, Michigan and Illinois (combined because of
controls were enrolled. Eligibility for this analysis was restricted to sample size and regional similarities), Georgia and Tennessee
participants for whom data on body powder use and all covariates (combined because of sample size)]; education (high school,
were available, resulting in a final sample size of 584 cases and 745 some after high school training, college or graduate degree);
controls; of these, 49 cases and 16 controls completed the short parity (0, 1, 2, 3þ); duration of oral contraceptives (never, <60
questionnaire. months, 60 months); history of tubal ligation (yes/no);
family history of breast or ovarian cancer in a first-degree
Exposure to body powder and talc relative (yes/no); smoking (ever/never); and body mass index
In the baseline interview, participants were asked whether (BMI < 25, 25–29.9, 30 kg/m2). Two class action lawsuits
they had ever regularly used talc, cornstarch, baby, or deodor- were filed in 2014 (21) concerning possible carcinogenic effects
izing powders. Participants were considered "regular users" if of body powder, which may have influenced recall of use.
they reported using any of these powders at least one time per Therefore, year of interview 2014 or later (yes/no) was included
month for at least 6 months, and "never users" if they did not. as a covariate in the logistic regression models. To assess
Regular users were asked about their frequency and duration of potential reporting bias, we also examined whether there were
use, age at first use, and whether they applied powders to differences in prevalence of reported powder use by interview
genital areas (including on underwear or sanitary napkins, or year (before 2014, 2014 and later) for cases and controls as well
on birth control devices like diaphragms) and/or nongenital as whether interview year was an effect modifier of the rela-
areas. Participants were categorized according to their type of tionship between powder use and EOC risk.

1412 Cancer Epidemiol Biomarkers Prev; 25(10) October 2016 Cancer Epidemiology, Biomarkers & Prevention
 Body Powder Use and Ovarian Cancer in African Americans

Analyses by the histologic subtype versus all controls were also Table 1. Characteristics of ovarian cancer cases and controls in the African
conducted and heterogeneity of risk estimates was tested by American Cancer Epidemiology Study (AACES)
seemingly unrelated regression (22). Because of the missing data Cases Controls
(n ¼ 584) (n ¼ 745)
for histology, 48 cases were omitted from these analyses. Through
n (%) n (%) P
stratified analyses, we also assessed possible effect modification of Age (years) <0.01
the association with powder use and ever use of HT among <40 31 (5.3) 80 (10.7)
postmenopausal women using logistic regression. Experimental 40–59 299 (51.21) 398 (53.4)
data show that the inflammatory response is enhanced in the 60þ 254 (43.5) 267 (35.8)
presence of estrogen and progesterone and we therefore tested for Range (years) 20–79 20–79
Education 0.02
interaction of the association with body powder use by meno-
High school or less 262 (44.9) 278 (37.3)
pausal status (20). Logistic regression and trend analyses were Some after high school training 145 (24.8) 210 (28.2)
performed using SAS version 9.4 (SAS Institute). College or graduate degree 177 (30.3) 257 (34.5)
Body mass index (kg/m2) 0.09
<24.9 (under- and normal weight) 86 (14.7) 140 (18.8)
Results 25–29.9 (overweight) 148 (25.3) 197 (26.4)
Descriptive statistics for cases and controls are presented >30 (obese) 350 (59.9) 408 (54.8)
Parity (# of live births) 0.06
in Table 1. Cases were older than controls and had lower educa-
0 105 (18.0) 96 (12.9)
tional achievement. Although this study was designed to match

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1 113 (19.4) 141 (18.9)
controls to cases by 5-year age group, the difference in the age at 2 136 (23.3) 198 (26.6)
diagnosis/age at interview may, in part, be because the study is 3þ 230 (39.4) 311 (41.6)
actively enrolling subjects. However, age ranges of cases (20–79 Tubal ligation 0.02
years) and controls (20–79 years) overlap. Significant differences Yes 201 (34.4) 302 (40.5)
No 383 (65.6) 443 (59.5)
in the distributions of well-established risk factors, including a
Oral contraceptive use <0.01
shorter duration of oral contraceptive use, and lower prevalence of Never 180 (30.8) 155 (20.8)
tubal ligation in cases as compared with controls, were as <60 months 230 (39.4) 334 (44.8)
expected. As expected, parity was lower among cases compared >60 months 174 (29.8) 256 (34.4)
with controls, but the difference was not significant. In addition, First-degree family history of breast <0.01
cases were more likely to report a family history of breast or or ovarian cancer
Yes 149 (25.5) 132 (17.7)
ovarian cancer. No significant difference in the median years of
No 435 (74.5) 613 (82.3)
use of body powder or occupational exposure of talc in cases Menopausal status 0.31
compared with controls was observed. Premenopausal 158 (27.2) 221 (29.7)
Table 2 shows the results of logistic regression models exam- Postmenopausal 423 (72.8) 522 (70.3)
ining the relationship between any use of body powder (either Hormone therapy 0.10
"only" nongenital powder or "any" genital powder) as well as the Ever use 118 (20.3) 125 (16.8)
Never use 463 (79.7) 618 (83.2)
use of body powder by type of application: "only" nongenital
Smoking 0.48
powder use or "any" genital powder use. Adjusting for potential Ever 257 (44.0) 313 (42.0)
confounders, we observed a significant positive association Never 327 (56.0) 432 (58.0)
between any powder use and EOC (OR ¼ 1.39; 95% CI, 1.10– Hysterectomya 0.43
1.76). The OR for the association with "any" genital powder use Yes 141 (24.1) 166 (22.3)
was 1.44 (95% CI, 1.11–1.86). An OR of 1.31 (95% CI, 0.95– No 443 (75.9) 579 (77.7)
Body powder use (median years)b 20 20 0.48
1.79) for the measure of association between "only" nongenital
Occupational talc exposurec 0.16
powder use and EOC was only slightly lower in magnitude Yes 58 (10.8) 62 (8.5)
compared with the association when "any" genital use was No 477 (89.2) 667 (91.5)
reported, but not statistically different from one another (P ¼ Histologic subtyped
0.56). In 2014 and later, we observed an increase in any powder Serous 393 (73.2)
use of 12% and 6% of cases and controls, respectively. Although Mucinous 24 (4.5)
Endometrioid 72 (13.4)
increased, these exposure prevalences were not significantly dif-
Clear cell 13 (2.4)
ferent from those interviewed before 2014 (P ¼ 0.30). For those Other 35 (6.5)
interviewed in 2014 or later, we observed an OR for "any" genital a
Defined as hysterectomy 2 years prior to diagnosis for cases and 2 years prior to
powder use of 2.91 (95% CI, 1.70–4.97) compared with 1.19 interview for controls.
(95% CI, 0.87–1.63) before 2014. We observed a weaker OR b
Among body powder ever users only.
c
of 1.26 (95% CI, 0.69–2.32) for 2014 and later compared with Data not available for participants who completed the short questionnaire
1.40 (95% CI, 0.96–2.03) before 2014 for those who reported (49 cases and 16 controls).
d
Data missing on histologic subtype for 47 cases.
"only" nongenital use. A test for effect modification by year of
interview was statistically significant (P ¼ 0.005).
The ORs for the association between daily use of powder for
either "only" nongenital powder use (OR ¼ 1.53; 95% CI, 1.00– moderately stronger association for 20 years of "any" genital
2.35) or "any" genital powder use (OR ¼ 1.71; 95% CI, 1.26– powder use (OR ¼ 1.51; 95% CI, 1.11–2.06) compared with <20
2.33) with EOC were larger in magnitude than ORs for less than years of use (OR ¼ 1.33; 95% CI, 0.95–1.86; Ptrend ¼ 0.02). No
daily use compared with never use but the test for trend was dose–response with years of use was detected for "only" nongen-
significant for only "any" genital powder use (Table 2). There is a ital powder use. The ORs for the number of lifetime applications

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 Schildkraut et al.

Table 2. Adjusted ORs for the associations between mode, frequency, and magnitude and not significant (OR ¼ 1.10; 95% CI, 0.76–1.58).
duration of body powder use and ovarian cancer in the AACES Compared with serous cases, larger and statistically significant
Cases Controls ORs are found for the associations with type of powder appli-
(n ¼ 584) (n ¼ 745) ORa
cation in nonserous EOC cases; ORs were 1.63 (95% CI, 1.04–
Exposure n (%) n (%) (95% CI)
Body powder use
2.55) and 2.28 (95% CI, 1.39–3.74), for "any" genital powder
Never use 217 (37.2) 351 (47.1) 1.00 (Referent) use and "only" nongenital powder use, respectively (Table 3). A
Ever use 367 (62.8) 394 (52.9) 1.39 (1.10–1.76) comparison of adjusted odds ratios between serous and non-
Body powder use by location serous histologic subtypes and powder use, detected a differ-
Never use 217 (37.2) 351 (47.1) 1.00 (Referent) ence in "only" nongenital powder use (P ¼ 0.008), but did not
Only nongenital use 119 (20.4) 140 (18.8) 1.31 (0.95–1.79)
detect significant differences in association for "any" genital
Any genital use 248 (42.5) 254 (34.1) 1.44 (1.11–1.86)
Interview date <2014 (n ¼ 351) (n ¼ 571)
powder use (P ¼ 0.50).
Never use 147 (41.9) 286 (48.4) 1.00 (Referent) The stratified results by menopausal status (Table 4) suggest
Only nongenital use 76 (21.7) 104 (17.6) 1.40 (0.96–2.03) differences in the association for exposure to "only" nongenital
Any genital use 128 (36.5) 201 (34.0) 1.19 (0.87–1.63) powder use among premenopausal where no association is
Interview date >2014 (n ¼ 233) (n ¼ 154) seen for "only" nongenital powder use, whereas the association
Never use 70 (30.0) 65 (42.2) 1.00 (Referent)
with the risk of EOC and "any" genital use is elevated. Among
Only nongenital use 43 (18.4) 36 (23.3) 1.26 (0.69–2.32)
Any genital use 120 (51.5) 53 (34.4) 2.91 (1.70–4.97)
postmenopausal women, we observed positive associations of
similar magnitude for both the association between EOC and

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Frequency of use
Never use 217 (37.3) 351 (47.2) 1.00 (Referent) "only" nongenital powder use (OR ¼ 1.49; 95% CI, 1.04–2.15)
Only nongenital use and "any" genital powder use (OR ¼ 1.41; CI, 1.03–1.92).
Less than daily 61 (10.5) 82 (11.0) 1.15 (0.78–1.71) However, tests of interaction indicate no evidence for interac-
Daily 58 (10.0) 58 (7.8) 1.53 (1.00–2.35)
tion by menopausal status for either route of exposure. Among
Ptrend 0.09
Any genital use
menopausal women, analyses stratified by HT use suggest a
Less than daily 88 (15.1) 119 (16.0) 1.12 (0.80–1.58) stronger association among users compared with nonusers of
Daily 158 (27.2) 134 (18.0) 1.71 (1.26–2.33) HT for both routes of applications, although we detected a
Ptrend <0.01 borderline, nonsignificant interaction for the associations with
Duration of use "any" genital body powder by HT use (P ¼ 0.06). The test for
Never use 217 (37.4) 351 (47.4) 1.00 (Referent)
interaction for nongenital body powder by HT use was not
Only nongenital use
<20 years 59 (10.2) 68 (9.2) 1.37 (0.91–2.07)
significant (P ¼ 0.76).
>20 years 60 (10.3) 70 (9.5) 1.28 (0.85–1.93) To further consider the underlying mechanism for the rela-
Ptrend 0.13 tionship between use of body powder and the risk of EOC, we
Any genital use calculated the association between both "only" nongenital
<20 years 101 (17.4) 118 (15.9) 1.33 (0.95–1.86) powder use and "any" genital powder use and having an upper
>20 years 144 (24.8) 134 (18.1) 1.52 (1.11–2.07)
respiratory condition. Controlling for case–control status, age
Ptrend 0.02
Lifetime body powder applications
at diagnosis/interview, study site, education, smoking, and
Never use 217 (37.4) 351 (47.4) 1.00 (Referent) BMI, we found ORs of 1.35 (95% CI, 0.89–2.05) and 1.45
Only nongenital use (95% CI, 1.03–2.05) for "only" nongenital and "any" genital
Below median (<3,600 60 (10.3) 72 (9.7) 1.35 (0.90–2.03) powder use, respectively, in relation to a reported respiratory
applications) condition, respectively (data not shown). A nonsignificant, but
Above median (>3,600 59 (10.2) 66 (8.9) 1.30 (0.86–1.97)
elevated OR of 1.26 (95% CI, 0.77–2.06) was observed with
applications)
Ptrend 0.14
occupational exposure to talc and respiratory conditions (data
Any genital use not shown).
Below median (<3,600 92 (15.9) 119 (16.1) 1.16 (0.83–1.63)
applications)
Above median (>3,600 152 (26.2) 133 (17.9) 1.67 (1.23–2.26) Table 3. Adjusted ORs for the associations between talc use and serous/
applications) nonserous EOC
Ptrend <0.01
a
Cases Controls
Adjusted for age at diagnosis/interview, study site, education, tubal ligation, Histologic subtypea n (%) n (%) ORb (95% CI)
parity, BMI, duration of OC use, first-degree family history of breast or ovarian
Serous (n ¼ 392)
cancer, and interview year.
Never use 156 (39.8) 351 (47.1) 1.00 (Referent)
Only nongenital use 71 (18.1) 140 (18.8) 1.10 (0.76–1.58)
Any genital use 165 (42.1) 254 (34.1) 1.38 (1.03–1.85)
of body powder at or above and below the median support a Nonserous (n ¼ 144)
dose–response with "any" genital powder use (Ptrend < 0.01) but Never use 44 (30.6) 351 (47.1) 1.00 (Referent)
not for nongenital powder use (Ptrend ¼ 0.14). Only nongenital use 42 (29.2) 140 (18.8) 2.28 (1.39–3.74)
A report of any occupational talc exposure, for those com- Any genital use 58 (40.3) 254 (34.1) 1.63 (1.04–2.55)
a
pleting the long baseline questionnaire, was found to be Test for interaction for association with powder use by serous and non-
positively, but not statistically significantly, associated with serous histologic subtype and route of body powder exposure was P ¼
0.008 for "only" nongenital powder use and P ¼ 0.50 for "any" genital
EOC (OR ¼ 1.31; 95% CI, 0.88–1.93; data not shown). Table 3
powder use.
shows an OR of 1.38 (95% CI, 1.03–1.85) for the association b
Adjusted for age at diagnosis/interview, study site, education, tubal ligation,
in serous cases with "any" genital powder use. Among serous parity, BMI, duration of OC use, first-degree family history of breast or ovarian
cases, the OR for "only" nongenital powder use was lower in cancer, and interview year.

1414 Cancer Epidemiol Biomarkers Prev; 25(10) October 2016 Cancer Epidemiology, Biomarkers & Prevention
 Body Powder Use and Ovarian Cancer in African Americans

Table 4. Adjusted ORs for the association between EOC risk and body powder by menopausal status and HT use
Premenopause Postmenopause
Cases (n ¼ 158) Controls (n ¼ 221) Cases (n ¼ 423) Controls (n ¼ 522)
Exposure n (%) n (%) ORa (95% CI) n (%) n (%) ORa (95% CI)
Body powder useb
Never use 59 (37.3) 103 (46.6) 1.00 (Referent) 157 (37.1) 247 (47.3) 1.00 (Referent)
Only nongenital use 22 (13.9) 42 (19.0) 0.90 (0.44–1.84) 97 (22.9) 98 (18.8) 1.49 (1.04–2.15)
Any genital use 77 (48.7) 76 (48.7) 1.50 (0.87–2.57) 169 (40.0) 177 (33.9) 1.41 (1.03–1.92)
HT ever/never usec,d,e
HT ever use
Never use 34 (32.1) 55 (48.7) 1.00 (Referent)
Only nongenital use 23 (21.7) 23 (20.4) 1.74 (0.77–3.92)
Any genital use 49 (46.2) 35 (31.0) 2.68 (1.33–5.40)
HT never use
Never use 122 (38.9) 191 (46.9) 1.00 (Referent)
Only nongenital use 73 (23.3) 75 (18.4) 1.51 (0.99–2.29)
Any genital use 119 (37.9) 141 (34.6) 1.24 (0.87–1.79)
a
Adjusted for age at diagnosis/interview, study site, education, tubal ligation, parity, BMI, duration of OC use, first-degree family history of breast or ovarian cancer,
and interview year.
b
Test for interaction between menopausal status and route of body powder exposure was nonsignificant for only non-genital use (P ¼ 0.21) and any genital use

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(P ¼ 0.85) compared with never use.
c
Restricted to postmenopausal women.
d
Test for interaction between HT use and only nongenital use was nonsignificant (P ¼ 0.76).
e
Test for interaction between HT use and any genital use was nonsignificant (P ¼ 0.06).

Discussion icant increased risk for nonserous EOC. In fact, we found a

statistically significant difference between associations by sub-
In the largest EOC case–control study in AA women to date, we type for "only" nongenital use. Given the inconsistency with
observed a positive association between regular use of powder previous published findings, it is also reasonable that under-
and EOC regardless of the route of application. Users of genital reporting genital powder use, such as abdominal powder use
powder were shown to have greater than a 40% increased risk of that reaches the genital area, may have led to a spurious result.
EOC compared with an increased risk of more than 30% among Another possible explanation for our finding may be that there
those who used only nongenital powder. The OR for the associ- is a higher inflammatory response in AAs compared with whites
ation with genital powder use in the current study is consistent (23–25). Our results also suggest that the route of powder
with the association reported in AA women by Wu and colleagues exposure may have different effects by histologic subtype. As
(14). Of note, a high proportion of EOC cases (63%) and controls most high-grade serous EOC, but not nonserous subtypes, arise
(53%) reported any use of body powder. A dose–response trend in the fallopian tubes (26), it is possible that direct exposure
was evident for median years of use or greater as well as median through the genital tract specifically affects this disease subtype.
number or greater of lifetime applications of "any" genital powder The association with any genital powder use and nonserous
but not for use of "only" nongenital powder. Our results support cases may be due to the overlap between genital and nongenital
that the association with "any" genital powder use is similar in powder use (83% of cases and 83% of controls). We were
premenopausal and postmenopausal women, whereas there unable to examine associations with "only" genital powder
appears to be an association with use of "only" nongenital powder users due to sample size considerations. In contrast, nongenital
use among postmenopausal but not premenopausal women. powder use may be related to inhalation of the exposure
Associations were found among nonserous EOC cases and among through the lungs. Several large pooled analyses have demon-
postmenopausal users of HT exposed to either genital or non- strated risk factor associations with inflammatory-associated
genital powder. exposures, such as smoking (27), endometriosis (28), and
Most previous case–control studies have not found an asso- obesity (29) with nonserous histologic subtypes of ovarian
ciation between nongenital powder use and ovarian cancer, cancer but not high-grade serous EOC, providing a plausible
including a large pooled analysis by Terry and colleagues who theoretical basis for differences we found in associations by
reported an adjusted OR of 0.98 (95% CI, 0.89–1.07; refs. 6, histologic subtype.
16). No prospective studies have evaluated nongenital powder Akin to talc powders, titanium dioxide (TiO2) is another
use, nor has any study examined these associations by histo- inert particle that induces an inflammatory response upon
logic subtype (17, 18). In the current study, the overall asso- inhalation and has been considered to be "possibly carcino-
ciation with nongenital use and EOC was similar to that for genic to humans" by IARC (2). Experimental evidence of
genital powder use though it did not reach statistical signifi- enhanced inflammation due to exposure to inert environmen-
cance possibly due to small numbers and random variation. tal particulates of TiO2 showed inhibition of phagocytic activity
However, we also did not find a dose–response relationship of alveolar macrophages in pregnancy, and was found to be
with frequency, duration, or lifetime applications of "only" associated with increased asthma risk in the offspring of BALB/
nongenital powder use. Furthermore, we did not detect a c mice exposed to TiO2. In this study, elevated estrogen levels
significant association with use of "only" nongenital powder during pregnancy were found to contribute to the resulting
among serous cases, whereas the OR for the association with asthma risk (20). Our findings also support that enhanced
use of "only" nongenital powder showed over a 2-fold signif- airway inflammation is due to exposure to inert particles.

www.aacrjournals.org Cancer Epidemiol Biomarkers Prev; 25(10) October 2016 1415

 Schildkraut et al.

Consistent with a recent study (15) where an association with case–control study such as AACES, especially due to heightened
powder use and asthma was reported, the relationship between awareness of the exposure as a result of two recent class action
body powder use and respiratory conditions likely reflects an lawsuits (21). Because of such publicity, we adjusted for date of
enhanced inflammatory response due to powder use, suggest- interview in the analysis. However, there is still a possibility that
ing a mechanism by which EOC risk is increased. Therefore, recall bias may have caused some inflation of the ORs. Although
lung inhalation of powder could be a biologically plausible our findings suggest that the publicity of the class action lawsuits
mechanism for the association between nongenital body pow- may have resulted in increased reporting of body powder use, our
der use and increased EOC risk, particularly in nonserous EOC data do not support that recall bias alone before 2014 versus 2014
cases. or later would account for the associations with body powder use
To further explore whether estrogen influences the inflam- and EOC. It is possible that the lawsuits sharpened memories of
matory response, we performed stratified analyses by meno- body powder use and improved the accuracy of reported use for
pausal status. We did not see a difference in the association with both cases and controls interviewed in 2014 or later. As the
premenopausal compared with postmenopausal use of "any" association with nongenital body powder use is not consistent
genital powder use, which is not consistent with a recent report with the published literature, the possibility of misclassification of
(15) where an association with premenopausal use but not exposure, residual confounding, or a chance finding cannot be
postmenopausal use was found. However, consistent with this ruled out as an explanation for the associations with nongenital
report, we found a stronger association between "any" genital powder use.
powder use and EOC among postmenopausal women who In summary, we found that the application of genital powder is

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reported HT use compared with nonusers. This finding is also associated with serous and nonserous EOC in AA women, a novel
consistent with experimental data showing that in the presence observation in this population that is consistent with some large
of estrogen and/or estrogen and progesterone, the ability of studies in whites. Our data are consistent with the notion that
macrophages to clear inert particulates is altered, enhancing the localized chronic inflammation in the ovary caused by exposure
inflammatory response leading to the development of asthma to genital powder contributes to the development of EOC.
in mouse offspring (20). It has also been proposed that chronic Although associations with nongenital powder use and EOC have
inflammation, resulting from exposure to body powder, wheth- not been previously reported, we cannot rule out the possibility
er through inhalation or through a transvaginal route, may that this relationship may be specific to AA women. The high
exert a suppressive effect on adaptive immunity, leading to prevalence of exposure to both genital and nongenital body
increased risk of EOC (30). These findings suggest that AA powder among AA women compared with the mostly white
women may be particularly susceptible to exposure to body subjects (41%), as in the large pooled analysis (6), underscores
powder due to having higher endogenous estrogen levels com- the importance of the study's findings. The results of the current
pared with white women (31, 32). Because of the limited study suggest that the use of body powder is an especially
sample size, we were not able to evaluate associations with important modifiable risk factor for EOC in AA women.
the timing or duration of HT use or the concurrent effects of
both HT and powder use. Tests for interaction of the associa- Disclosure of Potential Conflicts of Interest
tions in the stratified analyses by HT use were not significant No potential conflicts of interest were disclosed.
and our findings should be considered exploratory.
The results of the current study showed that genital powder use Authors' Contributions
was associated with ovarian cancer risk in AA women and are Conception and design: J.M. Schildkraut, A.G. Schwartz, P. Terry, P.G. Moorman
consistent with localized chronic inflammation in the ovary due Development of methodology: J.M. Schildkraut, P. Terry, F. Camacho, F. Wang,
to particulates that travel through a direct transvaginal route. The P.G. Moorman
dose–response observed for duration of genital powder use Acquisition of data (provided animals, acquired and managed patients,
provides further evidence for the relationship between genital provided facilities, etc.): J.M. Schildkraut, A.J. Alberg, E.V. Bandera, J.S. Barn-
holtz-Sloan, M.L. Bondy, M.L. Cote, E. Funkhouser, E.S. Peters, A.G. Schwartz,
powder and overall EOC risk. Our data suggest that the increased
P. Terry, S. Crankshaw, F. Camacho, P.G. Moorman
risk due to use of genital powder applies to both serous and Analysis and interpretation of data (e.g., statistical analysis, biostatistics,
nonserous histologic subtypes of EOC. Use of "only" nongenital computational analysis): J.M. Schildkraut, S.E. Abbott, M.L. Bondy,
powder was not found to be associated with the serous subtype, M.L. Cote, L.C. Peres, E.S. Peters, A.G. Schwartz, F. Camacho, F. Wang,
but our data suggest a relationship with nonserous EOC. The P.G. Moorman
association with serous EOC is consistent with several previous Writing, review, and/or revision of the manuscript: J.M. Schildkraut,
S.E. Abbott, A.J. Alberg, E.V. Bandera, J.S. Barnholtz-Sloan, M.L. Bondy,
studies (4, 6, 14–17). Only the pooled analysis found associations
M.L. Cote, E. Funkhouser, L.C. Peres, A.G. Schwartz, P. Terry, F. Camacho,
with the endometrioid and clear cell subtypes (6). The association P.G. Moorman
with any occupational talc exposure and EOC (OR ¼ 1.31; data Administrative, technical, or material support (i.e., reporting or orga-
not shown), though not statistically significant, is also consistent nizing data, constructing databases): P. Terry, S. Crankshaw, F. Camacho,
with the results for "only" nongenital powder use and suggest P.G. Moorman
other routes of exposure, aside transvaginal, may effect EOC risk. Study supervision: J.M. Schildkraut, S. Crankshaw, P.G. Moorman
A recent publication of data from the WHI, which did not find
an association with genital talc use and ovarian cancer (18), was Acknowledgments
accompanied by an editorial that emphasized the challenges in The authors thank the AACES interviewers, Christine Bard, LaTonda Briggs,
Whitney Franz (North Carolina), and Robin Gold (Detroit). The authors also
assessing the exposure to talc due to the reliance on self-report
thank the individuals responsible for facilitating case ascertainment across the
(33). This limitation in the measurement of the exposure variables ten sites including: Jennifer Burczyk-Brown (Alabama); Rana Bayakly, Vicki
in the current study needs to be considered when interpreting our Bennett and Judy Andrews (Georgia); the Louisiana Tumor Registry; Lisa
results. The possibility of differential misclassification exists in a Paddock, Natalia Herman, and Manisha Narang (New Jersey); Diana Slone,

1416 Cancer Epidemiol Biomarkers Prev; 25(10) October 2016 Cancer Epidemiology, Biomarkers & Prevention
 Body Powder Use and Ovarian Cancer in African Americans

Yingli Wolinsky, Steven Waggoner, Anne Heugel, Nancy Fusco, Kelly Ferguson, E. Funkhouser, E.S. Peters, A.G. Schwartz, P. Terry, and P.G. Moorman).
Peter Rose, Deb Strater, Taryn Ferber, Donna White, Lynn Borzi, Eric Jenison, Additional support was provided by the Metropolitan Detroit Cancer Surveil-
Nairmeen Haller, Debbie Thomas, Vivian von Gruenigen, Michele McCarroll, lance System with funding from the NCI, NIH, and the Department of Health
Joyce Neading, John Geisler, Stephanie Smiddy, David Cohn, Michele Vaughan, and Human Services (contract number HHSN261201000028C), and the Epi-
Luis Vaccarello, Elayna Freese, James Pavelka, Pam Plummer, William Nahhas, demiology Research Core, supported in part by the NCI Center (grant number
Ellen Cato, John Moroney, Mark Wysong, Tonia Combs, Marci Bowling, P30CA22453; to A.G. Schwartz and M.L. Cote) to the Karmanos Cancer
Brandon Fletcher, (Ohio); Susan Bolick, Donna Acosta, Catherine Flanagan Institute, Wayne State University School of Medicine.
(South Carolina); Martin Whiteside (Tennessee) and Georgina Armstrong and The costs of publication of this article were defrayed in part by the
the Texas Registry, Cancer Epidemiology and Surveillance Branch, Department payment of page charges. This article must therefore be hereby marked
of State Health Services. advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate
this fact.
Grant Support
This work was supported by the NCI (grant number R01CA142081; to J.M. Received December 14, 2015; revised May 2, 2016; accepted May 4, 2016;
Schildkraut, A.J. Alberg, E.V. Bandera, J. Barnholtz-Sloan, M.L. Bondy, M.L. Cote, published OnlineFirst May 12, 2016.

References
1. American Cancer Society. Cancer facts & figures 2015; 2015. 18. Houghton SC, Reeves KW, Hankinson SE, Crawford L, Lane D, Wactawski-
2. World Health Organization, International Agency for Research on Cancer. Wende J, et al. Perineal powder use and risk of ovarian cancer. J Natl Cancer

Downloaded from http://aacrjournals.org/cebp/article-pdf/25/10/1411/2280551/1411.pdf by guest on 04 October 2023

IARC monographs on the evaluation of carcinogenic risks to humans; Inst 2014;106:dju208.
2010. p. 1–413. 19. Schildkraut JM, Alberg AJ, Bandera EV, Barnholtz-Sloan J, Bondy M, Cote
3. Heller DS, Gordon RE, Westhoff C, Gerber S. Asbestos exposure and ML, et al. A multi-center population-based case–control study of ovarian
ovarian fiber burden. Am J Ind Med 1996;29:435–9. cancer in African-American women: the African American Cancer Epide-
4. Merritt MA, Green AC, Nagle CM, Webb PM. Talcum powder, chronic miology Study (AACES). BMC Cancer 2014;14:688.
pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian 20. Zhang Y, Mikhaylova L, Kobzik L, Fedulov A V. Estrogen-mediated
cancer. Int J Cancer 2008;122:170–6. impairment of macrophageal uptake of environmental TiO2 particles to
5. Rohl AN, Langer AM, Selikoff IJ, Tordini A, Klimentidis R, Bowes DR, et al. explain inflammatory effect of TiO2 on airways during pregnancy.
Consumer talcums and powders: mineral and chemical characterization. J Immunotoxicol 2015;12:81–91.
J Toxicol Environ Health 2009;2:255–84. 21. Drugwatch. Talcum powder lawsuits [Internet]; 2015 [cited 2015 Nov 11].
6. Terry KL, Karageorgi S, Shvetsov YB, Merritt MA, Lurie G, Thompson PJ, Available from: http://www.drugwatch.com/talcum-powder/lawsuits/
et al. Genital powder use and risk of ovarian cancer: a pooled analysis 22. Hosmer D, Lerneshow S. Applied logistic regression. 2nd ed. New York, NY:
of 8,525 cases and 9,859 controls. Cancer Prev Res 2013;6:811–21. John Wiley & Sons, Inc; 2000.
7. Ness RB, Grisso JA, Cottreau C, Klapper J, Vergona R, Wheeler J, et al. Factors 23. Khera A, McGuire DK, Murphy SA, Stanek HG, Das SR, Vongpatanasin W,
related to inflammation of the ovarian epithelium and risk of ovarian et al. Race and gender differences in C-reactive protein levels. J Am Coll
cancer. Epidemiology 2000;11:111–7. Cardiol 2005;46:464–9.
8. Booth M, Beral V, Smith P. Risk factors for ovarian cancer: a case-control 24. Albert MA, Glynn RJ, Buring J, Ridker PM. C-reactive protein levels among
study. Br J Cancer 1989;60:592–8. women of various ethnic groups living in the United States (from the
9. Chang S, Risch HA. Perineal talc exposure and risk of ovarian carcinoma. Women's Health Study). Am J Cardiol 2004;93:1238–42.
Cancer 1997;79:2396–401. 25. Paalani M, Lee JW, Haddad E, Tonstad S. Determinants of inflammatory
10. Cook RC, Fradet G, English JC, Soos J, M€ uller NL, Connolly TP, et al. markers in a bi-ethnic population. Ethn Dis 2011;21:142–9.
Recurrence of intravenous talc granulomatosis following single lung trans- 26. Bowtell DD, B€ ohm S, Ahmed AA, Aspuria P-J, Bast RC, Beral V, et al.
plantation. Can Respir J 1998;5:511–4. Rethinking ovarian cancer II: reducing mortality from high-grade serous
11. Mills PK, Riordan DG, Cress RD, Young HA. Perineal talc exposure and ovarian cancer. Nat Rev Cancer 2015;15:668–79.
epithelial ovarian cancer risk in the Central Valley of California. Int J Cancer 27. Faber MT, Kjær SK, Dehlendorff C, Chang-Claude J, Andersen KK, Høgdall
2004;112:458–64. E, et al. Cigarette smoking and risk of ovarian cancer: a pooled analysis of
12. Whittemore AS, Wu ML, Paffenbarger RS, Sarles DL, Kampert JB, Grosser S, 21 case-control studies. Cancer Causes Control 2013;24:989–1004.
et al. Personal and environmental characteristics related to epithelial 28. Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, et al.
ovarian cancer. II. Exposures to talcum powder, tobacco, alcohol, and Association between endometriosis and risk of histological subtypes of
coffee. Am J Epidemiol 1988;128:1228–40. ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol
13. Wong C. Perineal talc exposure and subsequent epithelial ovarian cancer: a 2012;13:385–94.
case-control study. Obstet Gynecol 1999;93:372–6. 29. Olsen CM, Nagle CM, Whiteman DC, Ness R, Pearce CL, Pike MC, et al.
14. Wu AH, Pearce CL, Tseng C-C, Templeman C, Pike MC. Markers of Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian
inflammation and risk of ovarian cancer in Los Angeles County. Cancer Association Consortium. Endocr Relat Cancer 2013;20:251–62.
Int J Cancer 2009;124:1409–15. 30. Cramer DW, Finn OJ. Epidemiologic perspective on immune-surveillance
15. Cramer DW, Vitonis AF, Terry KL, Welch WR, Titus LJ. The association in cancer. Curr Opin Immunol 2011;23:265–71.
between talc use and ovarian cancer: a retrospective case-control study in 31. Pinheiro SP. Racial differences in premenopausal endogenous hormones.
two US states. Epidemiology 2016;27:334–46. Cancer Epidemiol Biomarkers Prev 2005;14:2147–53.
16. Cramer DW, Liberman RF, Titus-Ernstoff L, Welch WR, Greenberg ER, 32. Setiawan VW, Haiman CA, Stanczyk FZ, Le Marchand L, Henderson BE.
Baron JA, et al. Genital talc exposure and risk of ovarian cancer. Int J Cancer Racial/ethnic differences in postmenopausal endogenous hormones: the
1999;81:351–6. multiethnic cohort study. Cancer Epidemiol Biomarkers Prev 2006;15:
17. Gertig DM, Hunter DJ, Cramer DW, Colditz GA, Speizer FE, Willett WC, 1849–55.
et al. Prospective study of talc use and ovarian cancer. J Natl Cancer Inst 33. Wentzensen N, Wacholder S. Talc use and ovarian cancer: epidemiology
2000;92:249–52. between a rock and a hard place. J Natl Cancer Inst 2014;106:dju260.

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