Ovarian cancer risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The risk of developing ovarian cancer appears to be affected by several factors; in fact, early age at first pregnancy, older ages of final pregnancy, and the use of low dose hormonal contraception have been associated with a lower incidence of ovarian cancer. There is good evidence that in some women genetic factors are important.

Risk Factors

Fertility medication The link to the use of fertility medication, such as Clomiphene citrate, has been controversial. An analysis in 1991 raised the possibility that use of drugs may increase the risk of ovarian cancer.[1]

Genetic factors There is good evidence that in some women genetic factors are important. Carriers of certain mutations of the BRCA1 or the BRCA2 gene and certain populations (e.g. Ashkenazi Jewish women) are at a higher risk of both breast cancer and ovarian cancer, often at an earlier age than the general population. Patients with a personal history of breast cancer or a family history of breast and/or ovarian cancer, especially if at a young age, may have an elevated risk. A strong family history of uterine cancer, colon cancer, or other gastrointestinal cancers may indicate the presence of a syndrome known as hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch II syndrome), which confers a higher risk for developing ovarian cancer. Patients with strong genetic risk for ovarian cancer may consider the use of prophylactic i.e. preventative oophorectomy after completion of child-bearing.


The most important risk factor for ovarian cancer is a family history of a first-degree relative (e.g., mother, daughter, or sister) with the disease. Approximately 20% of ovarian cancers are familial, and although most of these are linked to mutations in the BRCA1 or BRCA2 genes, several other genes have been implicated in familial ovarian cancers.[6,7] The highest risk appears in women who have two or more first-degree relatives with ovarian cancer.[8] The risk is somewhat less for women who have one first-degree and one second-degree relative (grandmother or aunt) with ovarian cancer.


Known risk factors

There is convincing evidence that the following factors increase your risk of developing epithelial ovarian cancer and tumours of borderline malignancy.

Family history of ovarian cancer

Sometimes more cases of ovarian cancer develop in a family than would be expected by chance. A family history of ovarian cancer means that one or more close blood relatives have or had ovarian cancer. Sometimes it is not clear whether the family’s pattern of cancer is due to chance, shared lifestyle factors, a genetic risk passed from parents to children or a combination of these factors.

Having several relatives who have ovarian cancer can increase your risk of ovarian cancer. About 5%–10% of women with ovarian cancer have a family member who also has this disease. Having relatives with ovarian cancer on either your mother’s or your father’s side of the family increases your risk.

The risk of developing ovarian cancer is increased if:

One first-degree relative (mother, sister or daughter) has ovarian cancer, especially if they were diagnosed with ovarian cancer before the age of 50 or before they went into menopause. Women who have a mother diagnosed with ovarian cancer are at a higher risk than women who have a daughter diagnosed with ovarian cancer. Two or more first-degree relatives have been diagnosed with ovarian cancer. One first-degree relative and one second-degree relative (aunt, grandmother or niece) have been diagnosed with ovarian cancer. This combination means you have a slightly higher risk for ovarian cancer. Back to top

BRCA gene mutations

Only a small number of ovarian cancers (about 5%–10%) are related to a specific inherited genetic abnormality. Breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2) normally help control the growth of cancer cells. BRCA gene mutations were first found in women with breast cancer. They also increase the risk of ovarian cancer. These mutations can be inherited from either parent.

While mutations in BRCA1 or BRCA2 genes increase the risk of ovarian cancer, not all women with mutations in these genes will develop ovarian cancer.

Overall, BRCA1 increases the risk of ovarian cancer more than BRCA2. Ovarian cancer is more likely to occur before age 50 in women with BRCA1 mutations. Ovarian cancer is more likely to occur after age 60 in women with BRCA2 mutations.

BRCA gene mutations may be suspected in families if:

Ovarian cancer occurs in 3 or more first-degree relatives (mother, sisters or daughters). Breast or ovarian cancer develops at a younger age in several first-degree relatives, including at least 2 relatives who have breast cancer and 2 who have ovarian cancer. Ovarian cancers related to BRCA gene mutations are different from ovarian cancers in the general population of women (sporadic ovarian cancer). These cases of ovarian cancer are typically diagnosed at a younger age. The average age of diagnosis is 48 years for genetic forms, compared to 52 years for sporadic ovarian cancer.

Serous epithelial tumours are more commonly linked to BRCA gene mutations than sporadic forms of ovarian cancer. Having ovarian cancer linked to a BRCA gene mutation also increases the risk of developing papillary serous carcinoma of the peritoneum, which is a cancer in the lining of the abdominal cavity. But there may be a more favourable prognosis for forms of the disease linked to BRCA gene mutations.

Women with ovarian cancer related to a BRCA gene mutation are also at higher than average risk of developing breast and other cancers. Talk to your doctor about your risks. Genetic risk assessment and genetic testing may be an option for some women.


Lynch syndrome

Lynch syndrome (also called hereditary non-polyposis colorectal cancer, or HNPCC) is an uncommon genetic condition that increases the risk of colorectal and other cancers, including ovarian cancer. Women with type B Lynch syndrome, or Lynch II, have a higher risk of developing epithelial ovarian cancer in their lifetime.


Never being pregnant

Women who have never been pregnant have a higher risk of developing ovarian cancer than women who have been pregnant. Researchers are not sure if the lower risk in women who have been pregnant is due to the hormones that are present during pregnancy, which may have a protective effect. It is also unclear if the higher risk in women who have never been pregnant is linked to the factors that may make it difficult for her to become pregnant.

The risk for ovarian cancer is also higher in women who have never given birth (nulliparous), whether or not they have ever been pregnant. Researchers are not sure if this increased risk is related to the same factors that increase the risk of ovarian cancer in women who have never been pregnant.


Family history of certain cancers

Women who have a family history of breast cancer have a higher risk of developing ovarian cancer. A strong family history of uterine cancer, colon cancer, or other gastrointestinal cancers may indicate the presence of a syndrome known as hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch II syndrome), which confers a higher risk for developing ovarian cancer.


Personal history of breast cancer

Women who have been diagnosed with breast cancer have a higher risk of developing ovarian cancer. This could be because of a BRCA gene mutation. Some of the same risk factors for breast cancer that are related to a woman's menstruation history may also increase her risk of developing ovarian cancer. These risk factors include starting your period at an early age (younger than 11) or starting menopause at a later age (after age 55).


Ashkenazi Jewish ancestry

Studies have shown that women of Ashkenazi Jewish descent (Eastern European ancestry) are more likely than women in the general population to carry mutations of the BRCA1 and BRCA2 genes. About 1 in 40 Ashkenazi Jewish women carry a BRCA gene mutation, while 1 in 500 women in the general population have the gene mutation. Women with these mutations have a higher chance of developing ovarian cancer.


Hormone replacement therapy

Hormone replacement therapy (HRT) is used to manage the symptoms of menopause, such as hot flashes, vaginal dryness and mood swings. Research shows that using estrogen alone as HRT increases the risk of ovarian cancer. This risk increases with the length of time that the woman takes estrogen.

It is not clear if HRT that uses both estrogen and progestin (combined HRT) increases the risk for ovarian cancer.


Smoking

Smoking increases a woman’s risk of developing mucinous epithelial tumours of the ovary.


Asbestos

Studies have found that women who are heavily exposed to asbestos, especially in the workplace, are at an increased risk of developing ovarian cancer. Other studies have shown that asbestos fibres can accumulate in the ovaries of women exposed to it.


Possible risk factors

The following factors have been linked with ovarian cancer, but there is not enough evidence to say they are known risk factors. Further study is needed to clarify the role of these factors for ovarian cancer.

Being obese

Being obese means having a body mass index, or BMI, of 30 or more. Some studies have shown that being obese may slightly increase the risk of developing ovarian cancer.

Using talc on the genitals

Research studies on the use of talc on the genital, or perineal, area and the risk of ovarian cancer have had mixed results. Some studies show an increased risk, while others do not. Some research suggests that in the past certain sources of talcum powder may have been contaminated with asbestos or may have contained asbestiform fibres, which are fibres that have similar properties as asbestos. Health Canada now ensures that talcum powder does not contain asbestos. Talcum powders made with cornstarch do not increase the risk of ovarian cancer.

Endometriosis

The endometrium is the lining of the uterus. Endometriosis occurs when the endometrium grows outside of the uterus. It can grow on the ovaries, behind the uterus or on the intestines (bowels) or bladder. A recent Canadian study suggested that ovarian cancer and endometriosis may have a similar origin. Other studies have suggested that a woman’s risk of developing ovarian cancer may be higher if she has endometriosis, especially if the endometriosis involves the ovaries. Other studies have shown that the risk of certain types of ovarian cancer, including clear cell and endometrioid tumours, may be higher in women with endometriosis.

Tall adult height

Studies have shown that tall women have a slightly higher risk of ovarian cancer. Researchers think this increased risk may be due to growth and puberty hormones, rather than being tall by itself.



References

  1. Brinton LA, Moghissi KS, Scoccia B, Westhoff CL, Lamb EJ (2005). "Ovulation induction and cancer risk". Fertil. Steril. 83 (2): 261–74, quiz 525-6. doi:10.1016/j.fertnstert.2004.09.016. PMID 15705362.

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