Literature Review

Perineal use of talc and risk of ovarian cancer

Article· Literature Review (PDF Available)inJournal of epidemiology and community health 62(4):358-60 · May 2008with 404 Reads
DOI: 10.1136/jech.2006.047894 · Source: PubMed
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.
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.
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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).
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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
  • Article
    Background: It has been posited that there is an association between perineal talc use and the incidence of ovarian cancer. To date, this has only been explored in observational studies. Objectives: To perform a meta-analysis to evaluate the association between perineal talc use and risk of ovarian cancer. Methods: Studies were identified using six electronic databases. Observational studies involving at least 50 cases of ovarian cancer were eligible for inclusion. We analyzed the association between ovarian cancer, including specific types, and any perineal talc use, long-term (>10 year) use, total lifetime applications, and use on diaphragms or sanitary napkins. A sub-group analysis was performed, stratifying by study design and population. Results: We identified 24 case-control (13421 cases) and three cohort studies (890 cases, 181 860 person-years). Any perineal talc use was associated with increased risk of ovarian cancer (OR=1.31, 95%CI 1.24-1.39). >3600 lifetime applications (OR=1.42, 95%CI 1.25-1.61) was slightly more associated with ovarian cancer than <3600 (OR=1.32, 95%CI 1.15-1.50). An association with ever use of talc was found in case-control studies (OR=1.35, 95%CI 1.27-1.43), but not cohort studies (OR=1.06, 95%CI 0.90-1.25). However, cohort studies found an association between talc use and invasive serous type ovarian cancer (OR=1.25, 95%CI 1.01-1.55). We found an increased risk of serous and endometrioid but not mucinous or clear cell subtypes. Conclusions: In general, there is a consistent association between perineal talc use and ovarian cancer. Some variation in the magnitude of the effect was found when considering study design and ovarian cancer subtype.
  • Article
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  • Article
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  • Chapter
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  • Article
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  • Chapter
    This chapter discusses the background and uses, physical and chemical properties, environmental fate and bioaccumulation, mammalian toxicology, industrial hygiene and risk assessment of naturally occurring mineral fibers. Certain mineral fibers include asbestos, erionite and other zeolites, and mineral talc. Asbestos minerals have been known for their useful properties for millennia, and were widely used in the early twentieth century because of characteristics such as superb performance as a flame retardant, low thermal conductivity, tensile strength, and resistance to thermal, electrical, and chemical damage. Asbestos fibers can be released into the air when asbestos containing materials are mined, manufactured, used, or demolished. Fibrous zeolites are not expected to bioaccumulate. Natural fibrous zeolites can be released to the environment from mining or in refined form. True mineral fibers can be present in other forms of talc, either due to asbestos contamination or due to the presence of asbestiform fibers of talc.
Literature Review
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • Article
    A hospital-based case-control study of the association between fiber exposure and the development of epithelial ovarian cancer was performed at the Johns Hopkins Hospital in Baltimore, Maryland. Genital and respiratory fiber exposures were ascertained from incident cases (N = 77) and age-race matched controls (N = 46) using a structured questionnaire. Cases were ascertained between 1981 and 1985. An increased risk was observed for exposure to talc on sanitary napkins (OR = 4.79, 95% CI, = 1.29–17.79), genital fiber exposure from different sources for a long (cumulative exposure ⩾37.4 years) length of time (OR = 2.35, 95% CI = 0.95–5.80), and occupational fiber exposure in relatives (OR = 2.81, 95% CI = 0.90–8.75). A negative association was observed for antecedent tubal ligation (OR = 0.15, 95% CI = 0.027–0.88). Findings from this study should be confirmed in larger investigations.
  • Article
    A hospital-based case-control study of ovarian cancer was conducted in London and Oxford between October 1978 and February 1983. Menstrual characteristics, reproductive and contraceptive history and history of exposure to various environmental factors were compared between 235 women with histologically diagnosed epithelial ovarian cancer and 451 controls. High gravidity, hysterectomy, female sterilisation and oral contraceptive use were associated with a reduced risk of ovarian cancer. Infertility and late age at menopause were associated with an increase in risk. While these factors were related, they were each found to be independently associated with ovarian cancer risk after adjusting for the effect of the other factors.
  • Article
    Harlow, B. L (Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115), and N. S. Weiss. A case-control study of borderline ovarian tumors: the influence of penneal exposure to talc. Am J Epidemiol 1989;130:390-4. The authors intervIewed 116 female residents of western Washington State with serous and mucinous borderline ovarian tumors diagnosed between 1980 and 1985 and questioned them on their use of hygienic powders. A sample of 158 control women from the same counties were identified through random digit dialing and were interviewed as well. Neither the perineat application of baby powder nor the perineal application of cornstarch was associated with an appre ciably altered risk of borderline ovarian tumors. However, women who used deodorizing powders alone or In combination with other talc-containing powders had 2.8 times the risk (95% confidence Interval 1.1-11.7) of women who had not had perineal exposure to powder. These results suggest that future studies of ovarian tumors in relation to the application of talc-containing powders should consider ascertainIng the specific type(s) of powder used.