Epidemiology of epithelial ovarian cancer.

TLDR: The current state of knowledge regarding the known and possible causes of epithelial ovarian cancer are summarized and some of the main theories of ovarian carcinogenesis are discussed.

Abstract: Globally, ovarian cancer is the seventh most common cancer in women and the eighth most common cause of cancer death, with five-year survival rates below 45%. Although age-standardised rates are stable or falling in most high-income countries, they are rising in many low and middle income countries. Furthermore, with increasing life-expectancy, the number of cases diagnosed each year is increasing. To control ovarian cancer we need to understand the causes. This will allow better prediction of those at greatest risk for whom screening might be appropriate, while identification of potentially modifable causes provides an opportunity for intervention to reduce rates. In this paper we will summarise the current state of knowledge regarding the known and possible causes of epithelial ovarian cancer and discuss some of the main theories of ovarian carcinogenesis. We will also briefly review the relationship between lifestyle and survival after a diagnosis of ovarian cancer.

Figures

Table 1. Summary of risk and protective factors for epithelial ovarian cancer

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Accepted Manuscript
Epidemiology of epithelial ovarian cancer
Penelope M. Webb, Susan J. Jordan
PII: S1521-6934(16)30091-8
DOI: 10.1016/j.bpobgyn.2016.08.006
Reference: YBEOG 1650
To appear in:
Best Practice & Research Clinical Obstetrics & Gynaecology
Received Date: 15 August 2016
Accepted Date: 17 August 2016
Please cite this article as: Webb PM, Jordan SJ, Epidemiology of epithelial ovarian cancer, Best Practice
& Research Clinical Obstetrics & Gynaecology (2016), doi: 10.1016/j.bpobgyn.2016.08.006.
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EPIDEMIOLOGY OF EPITHELIAL OVARIAN CANCER
Penelope M Webb
a,b
*
Susan J Jordan
a,b
a
QIMR Berghofer Medical Research Institute, Locked Bag 2000 Royal Brisbane Hospital,
Brisbane, Queensland 4029, Australia
b
School of Public Health, The University of Queensland, Public Health Building, Corner of
Herston Road & Wyndham Street, Herston Queensland 4006, Australia
*Corresponding author
QIMR Berghofer Medical Research Institute
Locked Bag 2000 Royal Brisbane Hospital
Brisbane
Queensland 4029
Australia
Phone: +61 7 3362 0281
Fax: +61 7 3845 3502
Email: penny.webb@qimrberghofer.edu.au
Susan Jordan
Email: susan.jordan@qimrberghofer.edu.au

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ABSTRACT
Globally, ovarian cancer is the seventh most common cancer in women and the eighth most
common cause of cancer death, with five-year survival rates below 45%. Although age-
standardised rates are stable or falling in most high-income countries, they are rising in many
low and middle income countries. Furthermore, with increasing life-expectancy, the number of
cases diagnosed each year is increasing. To control ovarian cancer we need to understand the
causes. This will allow better prediction of those at greatest risk for whom screening might be
appropriate, while identification of potentially modifable causes provides an opportunity for
intervention to reduce rates. In this paper we will summarise the current state of knowledge
regarding the known and possible causes of epithelial ovarian cancer and discuss some of the
main theories of ovarian carcinogenesis. We will also briefly review the relationship between
lifestyle and survival after a diagnosis of ovarian cancer.
[Words=148]
KEY WORDS
Ovarian neoplasms; epidemiology; incidence; risk factors; survival

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<A>INTRODUCTION
Globally, 240,000 women are diagnosed with ovarian cancer every year and, with five-year
survival below 45%, it is responsible for 150,00 deaths making it the 7
th
most common cancer
and 8
th
most common cause of cancer death among women [1]. Figure 1A shows that age-
standardised incidence rates are highest in northern and central/eastern Europe, intermediate in
north America, Australia and western Europe and lowest in Asia and Africa. Rates have been
decreasing in most high incidence countries but increasing in many low incidence countries
(Figure 1B) thus the differences today are less marked than 30 years ago [2]. Rates also vary by
ethnicity within countries such that in the United States, rates in non-Hispanic white women are
approximately 30% higher than African-American and Asian women and 12% higher than
Hispanic women [3].
<FIGURE 1 NEAR HERE>
Ovarian cancer is rare in women under 40 years of age and most cancers in this age group are
germ cell tumours. Above age 40, more than 90% are epithelial tumours and the risk increases
with age, peaking in the late 70s. Despite being classified as ovarian, a high proportion of high-
grade serous cancers are now thought to originate from the fallopian tube. In the following
discussion the term ‘ovarian cancer’ refers to epithelial cancers that arise in the ovary or
fallopian tube as well as the histologically similar primary peritoneal cancers.
<A>RISK FACTORS
It is well established that women with a family history of ovarian cancer are themselves at
higher risk of the disease. The risk for women with one affected first-degree relative is about
three times that for women with no affected relatives [4], and even higher for those whose

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relative was diagnosed below the age of 50 [5]. A high proportion of hereditary cancers are
due to mutations in the BRCA genes, however BRCA mutations are also common among
women with ovarian cancer who do not have a family history of either breast or ovarian
cancer [6]. BRCA1 mutation carriers have an estimated 40-50% risk of developing ovarian
cancer by age 70, compared to 10-20% for BRCA2 [7]. Most cancers associated with BRCA
mutations are high-grade serous tumors. Lynch syndrome or hereditary nonpolyposis colon
cancer (HNPCC) caused by mutations in genes involved in DNA mismatch repair also
increases risk of ovarian cancer, particularly non-serous cancer [8]. Mutations in other genes
including BRIP1 [9] and RAD51 [10] confer a moderately increased risk of ovarian cancer
and genomewide association studies have now identified more than 20 low-risk susceptibility
loci including CHEK2, WNT4, TERT, and ABO which are also associated with cancers at
other sites.
The following sections review non-genetic factors known or suspected to affect a woman’s
risk of developing epithelial ovarian cancer, with most weight given to recent meta-analyses
and pooled analyses, particularly those using data from prospective studies.
<B>Reproductive history
<C>Age at menarche and menopause
The relationship between age at menarche and ovarian cancer risk remains unclear. Although
one meta-analysis [11] reported a significantly reduced risk in those with an older age at
menarche, a recent pooled cohort analysis did not confirm this finding except in relation to
clear cell ovarian cancer [12]. The evidence is more consistent for age at menopause. The
pooled analysis found that each five-year increase in age at menopause was associated with a

Frequently asked questions

Q1. What are the main factors that affect the risk of ovarian cancer?

Higher parity, oral contraceptive use and tubal ligation all significantly reduce risk, while family history of ovarian or breast cancer, older menopausal age, obesity, menopausal hormone therapy use, a history of endometriosis and smoking increase risk. 

Q2. What is the common cause of cancer death in women?

ovarian cancer is the seventh most common cancer in women and the eighth most common cause of cancer death, with five-year survival rates below 45%. 

Q3. What is the common type of breastfeeding?

<C>Breastfeeding Several meta-analyses have concluded that parous women who breastfeed their children have a 20-25% lower risk of ovarian cancer than parous women who have not breastfed [21,22] and that longer durations of breastfeeding are associated with greater risk reductions. 

Q4. What is the association between physical activity and ovarian cancer?

<B>Physical activity and sedentary behaviour Vigorous physical activity can lead to anovulation and amenorrhoea and it may also reduce inflammatory biomarkers and enhance immune function, all of which would potentially reduce risk of ovarian cancer. 

Q5. What is the main reason for the increase in cases of ovarian cancer?

Ovarian cancer remains a significant cause of morbidity and mortality globally with rising rates in many low and middle income countries and increasing case numbers in high income countries because of population aging. 

Q6. What is the association between obesity and ovarian cancer?

Obesity is associated with low-grade chronic inflammation and fat cells produce inflammatory cytokines as well as converting androstenedione to oestrone [55]. 

Q7. What is the recent study to show a inverse association with hysterectomy?

The recent pooled analysis of cohort studies [12] also showed no overall inverse association with hysterectomy, but did report a 40% reduction in clear cell cancers. 

Q8. How many women with a family history of ovarian cancer are at higher risk?

The risk for women with one affected first-degree relative is about three times that for women with no affected relatives [4], and even higher for those whoseM ANUS CRIP TAC CEPT EDACCEPTED MANUSCRIPT4relative was diagnosed below the age of 50 [5].