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Perineal use of talc and risk of ovarian cancer

DOI:10.1136/jech.2006.047894
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H Langseth
H Langseth
H Langseth
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S E Hankinson
S E Hankinson
S E Hankinson
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Jack Siemiatycki at Université de Montréal
Jack Siemiatycki
Elisabete Weiderpass at International Agency for Research on Cancer
Elisabete Weiderpass
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Abstract

Ovarian cancer is one of the most common gynaecological neoplasms, especially in industrialised countries. The aetiology of the disease is not well understood, except that inherited mutations in the breast cancer genes BRCA-1 and BRCA-2 account for up to 10% of all cases, and child-bearing, oral contraceptive use and breast-feeding reduce the risk. Some environmental exposures, notably talc and asbestos, have been suspected as ovarian carcinogens.
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Perineal use of talc and risk of ovarian cancer
H Langseth,
1
S E Hankinson,
2
J Siemiatycki,
3
E Weiderpass
1,4,5
1
The Cancer Registry of
Norway, Institute of population-
based Cancer Research, Oslo,
Norway;
2
Channing Laboratory,
Department of Medicine,
Brigham and Women’s Hospital
and Harvard Medical School,
Boston, MA, USA;
3
Department
of Social and Preventive
Medicine, University of
Montreal, Montreal, Canada;
4
Department of Medical
Epidemiology and Biostatistics,
Karolinska Institutet, Stockholm,
Sweden;
5
Samfundet
Folkha¨lsan, Helsinki, Finland
Correspondence to:
E Weiderpass, The Cancer
Registry of Norway, 0310 Oslo,
Norway; eliwei@ki.se
Accepted 15 October 2007
ABSTRACT
Ovarian cancer is one of the most common gynaecological
neoplasms, especially in industrialised countries. The
aetiology of the disease is not well understood, except
that inherited mutations in the breast cancer genes BRCA-
1 and BRCA-2 account for up to 10% of all cases,
1
and
child-bearing, oral contraceptive use and breast-feeding
reduce the risk.
2
Some environmental exposures, notably
talc and asbestos, have been suspected as ovarian
carcinogens.
Talc refers to both mineral talc and industrial
products that contain mineral talc. Mineral talc
occurs naturally in many regions of the world and
is valued for its softness, platyness, and ability to
absorb organic matter. Mineral talc occurs natu-
rally in a platy (flat) form, but may also occur as
asbestiform fibres, which describes its physical
form and does not imply the presence of asbestos.
The purer forms (approximately 90% mineral talc)
are used for cosmetic and hygiene products
including baby powders and feminine hygiene
products. Perineal use of cosmetic talc is a common
practice in the United Kingdom, North America,
Australia and some other countries. To our knowl-
edge accurate estimates of prevalence of use of
cosmetic talc are not available. However, the use
for female hygiene of body powders, baby pow-
ders, talcum powders and deodorising powder,
most of which contain cosmetic talc in varying
amounts, has been reported to be as high as 50% in
some countries.
3
From pathological studies it is known that
particles and fibres that enter the body can migrate
to distant organs. For instance, asbestos fibres have
been found in ovaries from women exposed to
asbestos.
45
Analogously, following perineal appli-
cation, talc particles can migrate from the vagina to
the peritoneal cavity and ovaries.
6
A majority of
women experience retrograde menstruation
7
; this
suggests a mechanism by which talc particles can
travel through the female reproductive tract to the
ovaries. Furthermore, epidemiological studies have
shown decreased risks of ovarian cancer after tubal
ligation and/or hysterectomy, suggesting that
removing a pathway by which carcinogenic sub-
stances can reach the ovaries reduces the risk.
89
The association between talc use in the perineal
region and ovarian cancer was investigated in one
cohort study,
10
and 20 case-control studies.
11–30
In
the cohort study, arguably the strongest study
because of its partly prospective ascertainment of
exposure, there was no association between
cosmetic talc use and risk of all subtypes of ovarian
cancer combined. The various case-control studies
provided indications of either a significant excess
risk (10 studies) or non-significant excess risk or
null (10 studies), with odds ratios (ORs) ranging
from 1.0 to 3.9. None of the studies reported
relative risks below 1.0. The population-based case-
control studies,
11 15–17 20–26 28–30
included studies with
112–824 ovarian cancer cases, and had odds ratios
ranging from 1.1 to 3.9 (fig 1). The hospital-based
case control studies
12–14 18 19 27
included studies with
77–462 cases, and reported odds ratios between 1.0
and 2.5. Pooled odds ratios were calculated by fixed
effects model. As shown in figure 1 pooled ORs
were 1.40, 1.12 and 1.35 for population-based,
hospital-based and all case control studies com-
bined, respectively. Some studies
13 14 22 23 26 28
tried
to assess exposure-response associations, in terms
of frequency of use or length of use in years but
found no clear trend.
Methodological factors such as recall bias should
always be considered in case-control studies. It
could have been a problem had there been wide-
spread publicity about the possible association
between use of body powder and cancer. The
International Agency for Research on Cancer
(IARC) working group considers that there has
not been widespread public concern about this
issue and therefore considers it unlikely that such a
bias could explain the consistent findings. Another
source of recall bias could result from the fact that
women with the cancer tend to remember or over-
report their use of body powder. The influence of
this type of recall bias cannot be ruled out.
Eight of the population-based case-control stu-
dies
11 16 22–24 26 28 29
were identified, by the IARC
working group as being most informative in terms
of size of the studies, whether the studies were
population-based, participation rates and adjust-
ments of confounding variables. The selected studies
included at least 188 cases and had participation
rates ranging from 60% to 75%. Among these eight
studies, the prevalence of perineal use of talc-based
body powder among controls ranged from 16% to
52%. The relative risks of ovarian cancer among
body powder users were homogeneous across this
set of eight studies, each of which indicated a 30–
60% increase in risk. Among the other 12 case-
control studies, most also reported relative risks of
this magnitude or higher.
Information on talc use in infancy is generally
insufficient in the case-control studies. However, in
one study the exposure to baby powder was
reported by 42.2% of the cases and 40.5% of the
controls.
15
In several of the other studies patients
were asked about age at first use of perineal talc, as
an indicator for use in infancy or other periods of life.
Only four case-control studies
16 23 29 30
and one
cohort study
10
provided results by histological type.
In four of these studies, in particular the cohort
study, there were hints of higher risks of serous
tumours related to talc exposure.
Research report
358 J Epidemiol Community Health 2008;62:358–360. doi:10.1136/jech.2006.047894
Before 1976, talc was to some extent contaminated with
asbestos, so that the early studies relating talc to ovarian cancer
may have been confounded by the asbestos.
31
However, the
association between talc exposure and ovarian cancer is as
strong in recent studies,
28 29
as in earlier ones, diminishing the
likelihood that all these results are influenced by contamination
of talc by asbestos.
To summarise the evidence in favour of an association, a very
large number of studies have found that women who used talc
experienced excess risks of ovarian cancer; some results were
statistically significant and some were not. There was some
indication in the cohort study of an increase in serous tumours.
The evidence of talc migrating to the ovaries lends credibility to
such a possible association. The main epidemiological evidence
against the association is the absence of clear exposure-response
associations in most studies, as well as the absence of an overall
excess risk in the cohort study.
On balance, the epidemiological evidence suggests that use of
cosmetic talc in the perineal area may be associated with
ovarian cancer risk. The mechanism of carcinogenicity may be
related to inflammation.
32
The carcinogenicity of non-asbestiform talc was assessed by a
monograph working group at IARC in 2006.
33
After considering
biases and possible confounding factors, the IARC working
group concluded that the epidemiological studies provided
limited evidence for the carcinogenicity of perineal use of talc-
based body powder, and classified this use as possibly
carcinogenic to human beings (that is, group 2B).
34
PROPOSAL: TO RESEARCH COMMUNITY
The current body of experimental and epidemiological evidence
is insufficient to establish a causal association between perineal
use of talc and ovarian cancer risk. Experimental research is
needed to better characterise deposition, retention and clearance
of talc to evaluate the ovarian carcinogenicity of talc.
The majority of the epidemiological studies carried out so far
have been among American women. It would be instructive to
seek evidence in other countries where perineal use of talc has
been common.
While there has been some efforts to measure the degree of
use, these have mainly been measured simply as the reported
years of use. It is possible that the ostensible lack of exposure
response trends is the result of crudeness of the exposure metric
used. Therefore, it is important that future studies, irrespective
of study design, devote some effort to better assessment of
exposure. The use of body powders should be assessed both in
terms of calendar time and age of the subject. Subjects should be
asked about lifetime use, including age at initial use (infancy,
childhood, teenager years, adulthood), age at which they
stopped using such powders, gaps in the lifetime period of use
Figure 1 Results from case-control studies contributing data on perineal talc use and ovarian cancer. Results are presented as odds ratios (ORs) and
their corresponding confidence intervals (95% CIs) and represented by squares and lines, respectively. Results are separated in 14 population-based
and six hospital-based case-control studies. Pooled ORs for all population-based studies combined and all hospital-based studies combined are given.
OR pooling by fixed effect models (Mantel-Haenszel method).
Research report
J Epidemiol Community Health 2008;62:358–360. doi:10.1136/jech.2006.047894 359
and frequency and nature of use (daily, during certain seasons of
the year, only while menstruating). Another important ques-
tion is whether the use of body powder was before or after tubal
ligation or hysterectomy.
Individuals’ answers to questions about use of brand names
over time may be unreliable, and therefore, in future studies,
investigators should try to ascertain, either from government or
industry sources, the composition of the powders used in
different time periods by different brand names and, in
particular, to ascertain whether the exposure may have included
some contamination by asbestos and also whether the exposure
was to talc or a non-talc product. Statistical analyses should
attempt to assess risk separately for the categories of powders:
talc containing asbestos, talc not containing asbestos, non-talc
product. Further, exposure metrics should take into account the
age, duration and intensity of exposure. As well as analyses for
all ovarian tumours combined, there should, if possible, be
analyses by histological subtype and by invasiveness of the
tumour.
While it would not be reasonable to envisage establishing a
costly long-term prospective cohort study just to study this
association, any long-term cohort study that is being set up to
study cancer among women should collect information about
talc use if the study is being conducted in a country where such
use has been widespread.
In summary, future studies should focus on seeking evidence
in talc-exposed female populations worldwide, collecting reli-
able information on age at initial use of body powder, exposure
assessments and dose response associations.
Acknowledgements: The work reported in this paper was initiated while SH, JS and
EW were part of an IARC Monographs Working Group of the International Agency for
Research on Cancer, Lyon, France.
Funding: This study was financed by the Cancer Registry of Norway.
Competing interests: None.
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What this study adds
c Epidemiological evidence suggests that use of cosmetic talc in
the perineal area may be associated with ovarian cancer risk.
The IARC has classified this use of talc as possibly
carcinogenic to human beings (group 2B).
c The mechanism of carcinogenicity may be related to
inflammation. This paper focus on the high degree of
consistency in the studies accomplished so far, and what
should be the focus in future studies.
Research report
360 J Epidemiol Community Health 2008;62:358–360. doi:10.1136/jech.2006.047894
... Talc, the primary ingredient in baby powder, is a naturally occurring mineral known for its softness and absorbency and has been added to a broad range of personal care products since the early part of the twentieth century. To date, there have been seven systematic reviews and pooled data studies [1][2][3][4][5][6][7] of the relationship between talcum powder products and ovarian cancer. All studies including retrospective case-control studies have found a positive association. ...
... All studies including retrospective case-control studies have found a positive association. [2][3][4][5][6][7] The most recent review by O'Brien 1 limited analysis to the four prospective cohort studies and in its main conclusion stated there was no statistically significant association between genital talc use and ovarian cancer. ...
... The point estimates are the same for each and the 95% CI almost identical. We include data for > 10,000 lifetime uses as this number is explicitly defined as perineal exposure (3) Shildkraut was the only study that included women recruited after two class action lawsuits were filed in 2014 concerning possible carcinogenic effects of body powder influencing recall of use. The study adjusted for individuals answering questions after 2014 to account for increased recall bias (4) Wu combined non-perineal with perineal exposures. ...
Association Between the Frequent Use of Perineal Talcum Powder Products and Ovarian Cancer: a Systematic Review and Meta-analysis
Article
Full-text available
  • Feb 2022
Background: Risk of ovarian cancer in women with frequent perineal talcum powder product is not well understood. Prior systematic reviews focused on ever use. The purpose of this study is to estimate the association between frequent (at least 2 times per week) perineal talcum powder use and ovarian cancer. Methods: A systematic review and meta-analysis was conducted according to meta-analysis of observational studies in epidemiology guidelines. Study protocol was prospectively registered at PROSPERO (registration number CRD42020172720). Searches were performed in PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials databases from their inception to August 2, 2021. Case-control and cohort studies were included if they reported frequent perineal talcum powder use and an adjusted odds ratio or hazard ratio for ovarian cancer. Review for inclusion, data extraction, and quality assessment (using the Newcastle-Ottawa Scale [NOS]) were performed independently by two reviewers. Pooled adjusted odds ratios with 95% confidence intervals were generated from the random effects model. Heterogeneity was quantified with I2 statistic. Funnel plot and Eger's test were performed to assess publication bias. Subgroup and sensitivity analyses were performed for testing the robustness of the overall findings. Results: Initial database searches returned 761 unique citations and after review, eleven studies describing 66,876 patients, and 6542 cancers were included (Cohen's κ = 0.88). Publication quality was high (median NOS = 8, range: 4 to 9). Frequent talcum powder use was associated with an elevated risk of ovarian cancer (adjusted pooled summary odds ratio 1.47 (95% CI 1.31, 1.65, P<0.0001). There was no evidence of bias and low heterogeneity (I2= 24%, P=0.22). There was no meaningful difference limiting analysis to publications with a NOS quality score of 8 or 9 or limiting studies based on study design. Conclusions: This review suggests an increased risk of ovarian cancer associated with frequent perineal powder exposure of 31-65%.
View
... The association between perineal talc use and ovarian cancer was examined in a number of epidemiology studies in the past 4 decades. Some casecontrol studies and meta-analyses reported associations, while other case-control investigations, three large prospective cohort studies, and a pooled analysis of cohort investigations found this association to be null (Cramer et al. 1999;Gross and Berg 1995;Huncharek, Geschwind, and Kupelnick 2003;Huncharek and Muscat 2011;Huncharek et al. 2007;IARC, 2010;Langseth et al. 2008;Musser 2014;NCI, 2016;O'Brien et al. 2020;Penninkilampi and Eslick 2018;Taher et al. 2019;Wentzensen and Wacholder 2014). ...
... A number of systematic reviews and meta-analyses of epidemiology evidence regarding talc exposure and ovarian cancer have been published (Cramer et al. 1999;Gross and Berg 1995;Huncharek, Geschwind, and Kupelnick 2003;Huncharek and Muscat 2011;Huncharek et al. 2007; International Agency for Research on Cancer (IARC) 2010; Langseth et al. 2008;Musser 2014; National Cancer Institute (NCI) 2016; Penninkilampi and Eslick 2018;Taher et al. 2019;Wentzensen and Wacholder 2014). These analyses reported similar findings of modest, positive meta-RRs among relevant case-control studies for ever vs. never talc use and no marked associations among cohort studies. ...
... These analyses reported similar findings of modest, positive meta-RRs among relevant case-control studies for ever vs. never talc use and no marked associations among cohort studies. It is noteworthy that several investigators indicated that the influence of recall bias could not be ruled out for case-control studies (Langseth et al. 2008;Penninkilampi and Eslick 2018;Taher et al. 2019). ...
A critical review of talc and ovarian cancer
Article
Full-text available
  • May 2020
The association between perineal talc use and ovarian cancer has been evaluated in several epidemiology studies. Some case-control studies reported weak positive associations, while other case-control and three large prospective cohort investigations found this association to be null. A weight-of-evidence evaluation was conducted of the epidemiology, toxicity, exposure, transport, in vitro, and mechanistic evidence to determine whether, collectively, these data support a causal association. Our review of the literature indicated that, while both case-control and cohort studies may be impacted by bias, the possibility of recall and other biases from the low participation rates and retrospective self-reporting of talc exposure cannot be ruled out for any of the case-control studies. The hypothesis that talc exposure induces ovarian cancer is only supported if one discounts the null results of the cohort studies and the fact that significant bias and/or confounding are likely reasons for the associations reported in some case-control investigations. In addition, one would need to ignore the evidence from animal experiments that show no marked association with cancer, in vitro and genotoxicity studies that did not indicate a carcinogenic mechanism of action for talc, and mechanistic and transport investigations that did not support the retrograde transport of talc to the ovaries. An alternative hypothesis that talc does not produce ovarian cancer, and that bias and confounding contribute the reported positive associations in case-control studies, is better supported by the evidence across all scientific disciplines. It is concluded that the evidence does not support a causal association between perineal talc use and ovarian cancer.
View
... Perineal exposure to cosmetic talc in women has been suspected as a cause of ovarian cancer for many years. Several studies have reported a positive association between use of talcum powder on the perineal area and ovarian cancer risk 18,19 . In a meta-analysis, data from 16 studies suggested that talc may increase ovarian cancer risk by 30% 19 . ...
... Several studies have reported a positive association between use of talcum powder on the perineal area and ovarian cancer risk 18,19 . In a meta-analysis, data from 16 studies suggested that talc may increase ovarian cancer risk by 30% 19 . ...
View
... P < 0.0001, I 2 = 33%), as presented in Fig. 2. This result is comparable to those of earlier meta-analyses conducted by other investigators [3,5,[65][66][67] as shown in Supplementary Material I. ...
... In total, the epidemiology studies suggest that perineal exposure to talc powder is a possible human ovarian carcinogen but there are concerns that the actual exposure experienced by these women over the past 40-50 years is not well understood. As reported by Langesth and colleagues [65], there had been some concern that asbestos-contaminated talc powder that was produced prior to 1976 might have been a confounder; however, the similarity of findings between studies published prior to and after this point suggests asbestos contamination does not explain the positive association between perineal use of talc powder and risk of ovarian cancer [25,26]. ...
Critical Review of the Association between Perineal Use of Talc Powder and Risk of Ovarian Cancer
Article
Over the past four decades, there has been increasing concern that perineal use of talc powder, a commonly used personal care product, might be associated with an increased risk of ovarian cancer. Objectives: To critically review all available human epidemiological data on the relationship between perineal use of talc powder and ovarian cancer, with consideration of other relevant experimental evidence. Methodology: We identified 30 human studies for qualitative assessment of evidence, including 27 that were retained for further quantitative analysis. Results: A positive association between perineal use of talc powder and ovarian cancer was found [OR: 1.28 (95% CI: 1.20 - 1.37)]. A significant risk was noted in Hispanics and Whites, in women applying talc to underwear, in pre-menopausal women and in post-menopausal women receiving hormonal therapy. A negative association was noted with tubal ligation. Conclusion: Perineal use of talc powder is a possible cause of human ovarian cancer.
View
... 33,36 Evidence from case-control and cohort studies also suggest an association between the use of cosmetic talc in the perineal area (e.g., to sanitary napkins, underwear, contraceptive devices, or directly to body) and increased risk of ovarian cancer. [37][38][39] A decade ago, the International Agency for Research on Cancer concluded that there was sufficient evidence that talc containing asbestiform fibers (referring to the mineral growth, not to the presence of asbestos) was a carcinogen, limiting the outcomes to mesothelioma and lung cancer, 5 and that there was limited evidence for the carcinogenicity of perineal use of talc-based body powder and classified it as Group 2B, possibly carcinogenic to humans. 40 Suggested potential carcinogenic mechanisms include chronic inflammation or contamination of talc with asbestos. ...
... 40 Suggested potential carcinogenic mechanisms include chronic inflammation or contamination of talc with asbestos. 5,38 This study is subject to at least the following limitations. Because of migration, state-specific cancer incidence rates may not reflect past asbestos exposure because the cancer may not have been diagnosed in the state where the asbestos exposure occurred, particularly given the long latency period between exposure and disease. ...
Geographic Co-Occurrence of Mesothelioma and Ovarian Cancer Incidence
Article
  • Jul 2019
Background: Asbestos is an established cause of several cancers, including mesothelioma and ovarian cancer. Incidence of mesothelioma, the sentinel asbestos-associated cancer, varies by state, likely reflecting different levels of asbestos exposure. We hypothesized that states with high mesothelioma incidence may also have high ovarian cancer incidence. Materials and Methods: Using data from the Centers for Disease Control and Prevention National Program for Cancer Registries and the National Cancer Institute Surveillance, Epidemiology, and End Results Program, we examined the geographic co-occurrence of mesothelioma and ovarian cancer incidence rates by U.S. state for 2003-2015. Results: By state, mesothelioma incidence ranged from 0.5 to 1.3 cases per 100,000 persons and ovarian cancer incidence ranged from 9 to 12 cases per 100,000 females. When states were grouped by quartile of mesothelioma incidence, the average ovarian cancer incidence rate was 10% higher in states with the highest mesothelioma incidence than in states with the lowest mesothelioma incidence. Ovarian cancer incidence tended to be higher in states with high mesothelioma incidence (Pearson correlation r = 0.54; p < 0.0001). Conclusions: Data from state cancer registries show ovarian cancer incidence was positively correlated with mesothelioma incidence, suggesting asbestos may be a common exposure. The potential for asbestos exposure has declined since the 1970s because fewer products contain asbestos; however, some products, materials, and buildings may still release asbestos and thousands of workers may be exposed. Ensuring that people are protected from exposure to asbestos in their workplaces, homes, schools, and communities may reduce the risk of several cancers.
View
... In 2006, the International Agency for Research Cancer declared talc a possible carcinogenic factor for humans (group 2B) [172,[208][209][210]. In 2008, Langseth et al. [211] reviewed 21 studies in which the perineal use of talc was found to be associated with ovarian cancer risk and suggested that the mechanism of carcinogenicity could be related to inflammation due to the latency between the age of the first use and the dose of exposure. Interestingly, a significantly increased risk was also found in women affected by borderline tumors of the ovary [212]. ...
Primary Ovarian Mesothelioma: A Case Series with Electron Microscopy Examination and Review of the Literature
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Full-text available
  • May 2021
Primary ovarian mesothelioma is a rare, aggressive neoplastic disease with a poor prognosis. At onset, the tumor is only rarely limited to the ovaries and usually already widespread in the peritoneum. The rarity of this entity and the difficulties differentiating it from either ovarian carcinoma or peritoneal mesothelioma may lead to frequent misdiagnoses and may raise some concerns about its histogenesis. Thus, reporting such rare cases is fundamental to gain greater awareness of this neoplasm and try to answer unsolved questions. Herein, we described four cases of histological diagnoses of ovarian mesothelioma extrapolated by the regional mesothelioma register of Apulia (southern Italy). In all cases, a detailed medical history was collected according to national mesothelioma register guidelines. A broad panel of antibodies was used for immunohistochemistry to confirm the diagnoses. Moreover, ovarian tissue samples were also examined by transmission and scanning electron microscopy, detecting asbestos fibers and talc crystals in two cases. Because of the few cases described, we reviewed the English literature in the Medline database, focusing on articles about ovarian mesothelioma “misclassification”, “misdiagnosis”, “diagnostic challenge” or “diagnostic pitfall” and on unsolved questions about its histogenesis and possible risk factors.
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... The International Agency for Research on Cancer (IARC) has recently concluded that even talc not contaminated by asbestiform fibres (a carcinogenic contaminant seen in talc in the past) is possibly carcinogenic to humans (class 2b) [26]. Epidemiology data suggest an increase in ovarian cancer risk for women who used cosmetic talc powder in the genital area [27,28]. Particles the size of talc, if they are present in the vagina, can traverse to the upper female genital tract and have been detected in and around tumourassociated immune cells, particularly inside the cytoplasm of macrophages in specimens from ovarian cancer patients with the history of perineal talc use [29]. ...
Transcriptomic and epigenomic effects of insoluble particles on J774 macrophages
Article
  • Oct 2020
Here we report epigenomic and transcriptomic changes in a prototypical J774 macrophage after engulfing talc or titanium dioxide particles in presence of estrogen. Macrophages are the first immune cells to engage and clear particles of various nature. A novel paradigm is emerging, that exposure to so-called 'inert' particulates that are considered innocuous is not really free of consequences. We hypothesized that especially the insoluble, non-digestible particles that do not release a known hazardous chemical can be underappreciated agents acting to affect the regulation inside macrophages upon phagocytosis. We performed gene chip microarray profiling and found that talc alone, and especially with oestrogen, has induced a substantially more prominent gene expression change than titanium dioxide; the affected genes were involved in pathways of cell proliferation, immune response and regulation, and, unexpectedly, enzymes and proteins of epigenetic regulation. We therefore tested the DNA methylation profiles of these cells via epigenome-wide bisulphite sequencing and found vast epigenetic changes in hundreds of loci, remarkably after a very short exposure to particles; ELISA assay for methylcytosine levels determined the particles induced an overall decrease in DNA methylation. We found a few loci where both the transcriptional changes and epigenetic changes occurred in the pathways involving immune and inflammatory signalling. Some transcriptomic and epigenomic changes were shared between talc and titanium dioxide, however, it is especially interesting that each of the two particles of similar size and insoluble nature has also induced a specific pattern of gene expression and DNA methylation changes which we report here.
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... Ovarian cancers are heterogeneous, but as a general category, they are the most lethal gynecologic malignancy [16]. Although many ovarian cancer cases have an uncertain etiology, BRCA mutations are involved in some cases [17][18][19]. The epidemiological association of ovarian carcinoma, i.e., cancers with epithelial cell origin, with talc use has been previously mentioned [4][5][6][7][8]. ...
Analytic comparison of talc in commercially available baby powder and in pelvic tissues resected from ovarian carcinoma patients
Article
Full-text available
Objective: Measure the size and shape of talc particles in talcum powder and compare this data to the size and shape of talc particles found in surgically resected tissues from patients with ovarian carcinoma. Methods: Using polarized light microscopy (PLM) and scanning electron microscopy (SEM), we measured the size and shape of talc particles in samples of talc-containing baby powder (TCBP) and surgically resected pelvic tissues (hysterectomies) from talc-exposed patients with ovarian carcinoma. Results: The most frequent class of particles in TCBP can be unequivocally identified as talc, using both polarized light microscopy and scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX). The talc particles found in resected tissues from ovarian carcinoma patients are similar in size and shape to the most abundant morphological class of particles in TCBP. Conclusions: This finding, combined with previous epidemiological literature and tissue-based analytical studies, provides further evidence that the small, isodiametric particles that dominate TCBP can migrate from the perineum and become lodged in distal structures in the female reproductive tract, where they may lead to an increased risk of developing ovarian carcinoma.
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... Since approximately this time talc has been thought to be asbestos-free; nevertheless the IARC concluded that even talc not containing asbestos is possibly carcinogenic to humans (class 2b) (Baan et al., 2006), however the mechanisms were not entirely clear. Dozens of epidemiologic studies (Booth et al., 1989;Chang and Risch, 1997;Chen et al., 1992;Cook et al., 1997;Cramer et al., 1999;Godard et al., 1998;Harlow et al., 1992;Harlow and Weiss, 1989;Mills et al., 2004;Ness et al., 2000a;Purdie et al., 1995;Rosenblatt et al., 1998;Tzonou et al., 1993;Whittemore et al., 1988;Wong et al., 1999;Gertig et al., 2000;Hankinson et al., 1993) have identified a 35% increase in ovarian cancer (OC) risk for women who used cosmetic talc powder in the genital area (Cramer et al., 2016;Langseth et al., 2008). While the association is being actively debated (Muscat and Huncharek, 2008), a recent epidemiologic study suggests the association is stronger for women who were premenopausal or were postmenopausal but taking estrogen replacement therapy (Cramer et al., 2016). ...
The effect of talc particles on phagocytes in co-culture with ovarian cancer cells
Article
  • Aug 2019
Talc and titanium dioxide are naturally occurring water-insoluble mined products usually available in the form of particulate matter. This study was prompted by epidemiological observations suggesting that perineal use of talc powder is associated with increased risk of ovarian cancer, particularly in a milieu with higher estrogen. We aimed to test the effects of talc vs. control particles on the ability of prototypical macrophage cell lines to curb the growth of ovarian cancer cells in culture in the presence of estrogen. We found that murine ovarian surface epithelial cells (MOSEC), a prototype of certain forms of ovarian cancer, were present in larger numbers after co-culture with macrophages treated to a combination of talc and estradiol than to either agent alone or vehicle. Control particles (titanium dioxide, concentrated urban air particulates or diesel exhaust particles) did not have this effect. Co-exposure of macrophages to talc and estradiol has led to increased production of reactive oxygen species and changes in expression of macrophage genes pertinent in cancer development and immunosurveillance. These findings suggest that in vitro exposure to talc, particularly in a high-estrogen environment, may compromise immunosurveillance functions of macrophages and prompt further studies to elucidate this mechanism.
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Epidemiology and Risk Factors for Ovarian Cancer
Chapter
  • May 2019
Ovarian cancer (OC) is the seventh most commonly diagnosed cancer in women and the eighth most common cause of death in them. The International Agency for Research on Cancer (IARC) reported that in 2012, gynecological cancers accounted for 20% of the 14.1 million new cancer cases and 8.2 million cancer deaths in females. Of this, 239,000 new cases were diagnosed as OC and caused 1,52,000 deaths. Epithelial OC is the predominant subtype with five other major histological subtypes. Rare inherited mutations account for a good number of OC cases. Factors like parity, oral contraceptive use, and lactation are protective, while older age at menopause and hormone replacement therapy (HRT) increase the risk. Cigarette smoking plays an important role in the pathogenesis, whereas the association with polycystic ovarian disease (PCOD), hysterectomy, and pelvic inflammatory disease (PID) is unclear. All the risk factors for development of ovarian cancer will be discussed in detail in the chapter.
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Prospective Study of Talc Use and Ovarian Cancer
Article
Full-text available
  • Mar 2000
Background: Perineal talc use has been associated with an increased risk of ovarian cancer in a number of case-control studies; however, this association remains controversial because of limited supporting biologic evidence and the potential for recall bias or selection bias in case-control studies. In this study, we conducted a prospective analysis of perineal talc use and the risk of ovarian cancer. Methods: The Nurses' Health Study is a prospective study of 121 700 female registered nurses in the United States who were aged 30-55 years at enrollment in 1976. Talc use was ascertained in 1982 by use of a self-administered questionnaire: after exclusions, 78 630 women formed the cohort for analysis. Three hundred seven epithelial ovarian cancers subsequently diagnosed in this cohort through June 1, 1996, were confirmed by medical record review and met inclusion criteria. Proportional hazards models by use of pooled logistic regression were used to derive relative risks (RRs) and 95% confidence intervals (CIs). Results: In 1982, 40.4% (n = 31 789) of the cohort reported ever using talc, and 14.5% (n = 11 411) reported ever using talc daily. We observed no overall association with ever talc use and epithelial ovarian cancer (multivariate RR = 1.09; 95% CI = 0.86-1.37) and no increase in risk of ovarian cancer with increasing frequency of use. There was a modest elevation in risk for ever talc use and invasive serous ovarian cancer (multivariate RR = 1.40; 95% CI = 1.02-1.91). The risk of epithelial ovarian cancer for talc users was not greater among women who had never had a tubal ligation (multivariate RR = 0.97; 95% CI = 0.71-1.32). Conclusion: Our results provide little support for any substantial association between perineal talc use and ovarian cancer risk overall; however, perineal talc use may modestly increase the risk of invasive serous ovarian cancer.
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Personal and environmental characteristics related to epithelial ovarian cancer. II. Exposures to talcum powder, tobacco, alcohol, and coffee
Article
Whittemore, A. S. (Stanford U. School of Medicine, Dept. of Health Research and Policy, Stanford, CA 94305–5092), M. L. Wu, R. S. Paffenbarger, Jr., D. L. Sarles, J. B. Kampert, S. Grosser, D. L Jung, S. Ballon, and M. Hendrickson. Personal and environmental characteristics related to epithelial ovarian cancer. II. Exposures to talcum powder, tobacco, alcohol, and coffee. Am J Epidemiol 1988;128:1228–40. Vaginal exposures to talc and other particulates may play an etiologic role in epithelial ovarian cancer. Surgical sterilization may protect against ovarian cancer by blocking entry of such particulates into the peritoneal cavity. The authors assessed histories of talcum powder use, tubal sterilization, and hysterectomy with ovarian conservation in 188 women in the San Francisco Bay Area with epithelial ovarian cancers diagnosed in 1983–1985 and in 539 control women. To investigate the roles of blood-borne environmental exposures on ovarian cancer risk, they assessed lifetime consumption of coffee, tobacco, and alcohol in these women. Of the 539 controls, 280 were hospitalized women without overt cancer, and 259 were chosen from the general population by random digit telephone dialing. Ninety-seven (52%) of the cancer patients habitually used talcum powder on the perineum, compared with 247 (46%) of the controls. Adjusted for parity, the relative risk (RR) = 1.40, p = 0.06. There were no statistically significant trends with increasing frequency or duration of talc use, and patients did not differ from controls in use of talc on sanitary pads and/or contraceptive diaphragms. Fewer ovarian cancer patients (7%) than controls (13%) reported prior fallopian tube ligation (RR, adjusted for parity, = 0.56, p = 0.06), and fewer patients (20%) than controls (28%) reported prior hysterectomy (RR = 0.66, p = 0.05). The protective effect of hysterectomy was confined to those who underwent this surgery 10 or more years prior to interview and to those who had not undergone prior tubal sterilization. Consumption of cigarettes and alcohol did not differ between cases and controls. By contrast, 11 (6%) cases never regularly consumed coffee, compared with 31 (11%) hospital controls and 26 (10%) population controls (RR, adjusted for smoking, = 2.2, p = 0.03, for the comparison using all controls). Overall, ovarian cancer risk among women who had drunk coffee for more than 40 years was 3.4 times that of women who had never regularly consumed coffee (p < 0.01). However, the data exhibited no clear trends in risk with increasing consumption. Although risk ratios relating duration of coffee drinking to ovarian cancer were unaffected by adjustment for several characteristics, further study is needed to exclude potential confounding by other unmeasured characteristics.
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Perineal Talc Exposure and Subsequent Epithelial Ovarian Cancer: A Case-Control Study
Article
Objective: To evaluate the role of talcum powder use as a risk factor for the development of epithelial ovarian cancer. Methods: In a case-control study, 499 patients with epithelial ovarian cancer were frequency matched for age at diagnosis (-5 years) with a control population of 755 patients. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, education, geographic location, history of tubal ligation, and previous hysterectomy. Results: Two hundred twenty-one of 462 patients (47.8%) in the study population and 311 of 693 patients (44.9%) in the control population had ever used talcum powder (OR 0.92; 95% confidence interval [CI] 0.24, 3.62). A significant association between duration of talc use and development of epithelial ovarian cancer was not demonstrable for 1-9 years (OR 0.9; 95% CI 0.6, 1.5), for 10-19 years (OR 1.4; 95% CI 0.9, 2.2), or for more than 20 years (OR 0.9; 95% CI 0.6, 1.2). To eliminate the possible confounding variable of surgery for the management of ovarian cancer, we omitted 135 patients in the study population who underwent hysterectomy within 5 years of the diagnosis of ovarian cancer. Within this subgroup of patients, tubal ligation or hysterectomy among talc users still failed to demonstrate an increased risk for the development of ovarian cancer (OR 0.9; 95% CI 0.4, 2.2). Conclusion: A significant association between the use of talcum powder and the risk of developing epithelial ovarian cancer is not demonstrable, even with prolonged exposure.
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Perineal Exposure to Talc and Ovarian Cancer Risk
Article
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 reported 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 a daily basis (OR 1.8, 95% CI 1.1-3.0), and 3) for more than 10 years (OR 1.6, 95% CI 1.0-2.7). The 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 lifetime 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. (C) 1992 The American College of Obstetricians and Gynecologists
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Asbestos exposure and ovarian fiber burden
Article
Epidemiologic studies suggest increased risk of epithelial ovarian cancer in female asbestos workers and increased risk of malignancy in general in household contacts of asbestos workers. Ovaries were studied from 13 women with household contact with men with documented asbestos exposure and from 17 women undergoing incidental oophorectomy. Ovarian tissue was examined by analytic electron microscopy.Significant asbestos fiber burdens were detected in 9 out of 13 women with household asbestos exposure (69.2%), and in 6 out of 17 women who gave no exposure history (35%). Three exposed women had asbestos counts over 1 million fibers per gram wet weight (23%), but only 1/17 women without an exposure history had a count that high (6%). Although asbestos has been documented as a contaminant of some older cosmetic talc preparations, the chrysotile and crocidolite types of asbestos we detected are more indicative of background and/or occupational exposure.This study demonstrates that asbestos can reach the ovary. Although the number of subjects is small, asbestos appears to be present in ovarian tissue more frequently and in higher amounts in women with a documentable exposure history. © 1996 Wiley-Liss, Inc.
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Hair dyes, analgesics, tranquilizers and perineal talc application as risk factors for ovarian cancer
Article
In a hospital-based case-control study of ovarian cancer conducted in Athens (1989-1991), 189 women with histologically confirmed common malignant epithelial tumors of the ovary were compared with 200 hospital visitor controls. All interviews were conducted by personal interview in the 2 participating hospitals and the data were analyzed by modelling through logistic regression, controlling for demographic and reproductive variables. Tranquilizing and hypnotic drugs (mostly diazepam) were not associated with risk of ovarian cancer: the adjusted relative risk (RR) and 95% confidence interval (CI) were 0.96 (0.57 to 1.63), whereas use of analgesics (mostly salicylates) was associated with significantly reduced risk of the disease (RR 0.51; CI 0.26 to 1.02). There was no evidence that perineal application of talc was associated with increased risk (RR 1.05; CI 0.28 to 3.98) but the frequency of reporting talc use was low in the study population. There was a statistically significant (p for trend 0.007) and a dose-dependent association between hair dyeing and risk of ovarian cancer. Compared to never-users, women dyeing their hair up to 4 times per year had a relative risk of 1.74 (0.91 to 3.32) whereas those dyeing their hair 5 or more times per year had a relative risk of 2.16 (1. 19 to 3.89).
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The epidemiology of ovarian cancer
Article
Ovarian cancer is the second most common cancer of the female reproductive system and the leading cause of death from gynecologic malignancies. In 1995, 26,600 women will be diagnosed with ovarian cancer in the U.S., and 14,500 women will die from the disease. Between 1986–1990, the overall age-adjusted incidence was 14.3/100,000 women; mortality was 7.8/100,000 women. Ovarian cancer, rare before age 40, increases steeply thereafter and peaks at ages 65–75. Incidence and mortality rates are higher among white women than among African-American women. Over the last three decades, ovarian cancer incidence has remained stable in high-risk countries, while an increasing trend has been reported in low-risk countries. Despite recent advancements in treatment, the overall five-year survival rates continues to be low (39%). Over 70% of ovarian tumors are diagnosed when regional or distant involvement has already occurred, causing survival rates to remain stable. The etiology of ovarian cancer is poorly understood. Most studies have focused on the epidemiology of invasive epithelial ovarian tumors, while few have explored the epidemiology of epithelial tumors of low malignant potential and nonepithelial tumors. Factors associated with an increased risk for invasive epithelial ovarian cancer include age, race, nulliparity, family history of ovarian cancer, and history of endometrial or breast cancer. Factors associated with a reduced risk are history of one or more full-term pregnancies, use of oral contraceptives, history of breast feeding, tubal ligation, and hysterectomy. Other factors such as infertility, fertility drugs, hormone replacement therapy, age at menarche, age at menopause, dietary factors, lactose intolerance, talc use, coffee and alcohol consumption have been suggested, but their role is still inconclusive.
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Risk Factors for Benign Serous and Mucinous Epithelial Ovarian Tumors
Article
Objective: To investigate the risk factors for benign serous and mucinous epithelial ovarian tumors. Methods: Cases were women newly diagnosed with benign serous ovarian tumors (n=230) or benign mucinous tumors (n=133) between 2002 and 2005. Control women were selected at random from the general population (n=752). All participants completed a comprehensive reproductive and lifestyle questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and to simultaneously adjust for potential confounding factors. Results: Current smoking was associated with a three-fold increase in risk of benign mucinous tumors (OR 3.25, 95% CI 1.97-5.34), and there was a trend of increasing risk with increasing amount smoked (P<.001). Both recent obesity (OR 1.93, 95% CI 1.30-2.88) and obesity at age 20 (OR 4.38, 95% CI 1.88-10.20) were associated with increased risk of benign serous ovarian tumors, and having had a hysterectomy was also related to increased risk of serous (OR 2.75, 95% CI 1.90-3.96), but not mucinous tumors. Ever having had a term pregnancy was inversely associated with both tumor types (combined OR 0.65, 95% CI 0.43-0.97), although greater numbers of pregnancies did not decrease risk further. Use of hormonal contraceptives was unrelated to risk. Conclusion: Our results suggest some differences in risk factors between benign serous and mucinous epithelial ovarian tumors and that risk factors for benign serous tumors differ from those well established for ovarian cancer. The results also suggest that there is potential for prevention of these common conditions through avoidance of smoking and obesity. Level of evidence: II.
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