Ovarian cancer risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Huda A. Karman, M.D.

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

• Common risk factors in the development of ovarian cancer include:
  • Age: there is a proportional association between age and ovarian cancer, as age increases, ovarian cancer incidence increases.
  • Hormonal and reproductive factors:
    • Early menarche and late menopause: both increase the frequency of the ovulation and the ovarian epithelium exposure to persistent injury
    • Nulliparity: studies have shown that multiparity and full term pregnancies decrease the risk of ovarian cancer and fallopian tubal carcinoma
    • Infertility:
    • Type of infertility and its causes should be taken in consideration as different causes can increase the risk of ovarian cancer such as
      • Primary infertility
      • Secondary infertility as endometriosis
      • The role of medications used for ovulation induction in increasing the risks of ovarian cancer is controversial. The association between the fertility drugs and ovarian cancer could be due to the stimulating effect of these drug, however this association is not a causal relation
      • Regardless to the fertility medications use, infertility is an independent risk factor of ovarian cancer
    • Endometriosis: Ovarian cancers that arise from endometriotic tissue usually affect young women and have better prognosis and survival rates
    • Polycystic ovarian syndrome: The association is controversial and complex. Meta-analysis found an association between PCOS and endometrial cancer in general but not with ovarian cancer specifically
    • Postmenopausal hormone therapy: a non statistical significant association found between combined estrogen-progesteron therapy and ovarian carcinoma. Meta-analysis found small significant association between ovarian cancer and estrogen therapy alone
    • Intrauterine device: regardless of the type of the IUD, studies have shown an increased risk of ovarian cancer with IUD use.
  • Genetic factors
    • BRCA gene mutations: the risk of both ovarian and breast cancers increases in women with BRCA mutations. The risk is more with BRCA1 carriers than BRCA2 carriers. Ovarian cancer develops at an earlier age in BRCA1-carrier women compared to BRCA2-carrier women. Serous adenocarcinoma is the most common type.General women and women with BRCA mutations usually present with stage III or IV. However, the grade is higher in women who are BRCA mutations' carries. The short-term survival rate of ovarian cancer in women with BRCA mutations is higher than non-carriers. Prophylactic bilateral salpingo-oophorectomy can be done in BRCA mutation carries who are at higher risk of developing fallopian tube cancer and primary peritoneal carcinoma
    • Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) : 1 percent of cases with ovarian cancer have Lynch syndrome.
    • Family history of breast cancer: BRCA mutation carriers with personal or family history of breast cancer have higher risk of developing ovarian cancer that those without BRCA mutation
    • Other genetic factors: the genes in the Fanconi anemias pathway can undergo different mutations and lead to the development of ovarian and/or breast cancer. The genes that are associated with ovarian cancer are: BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, PALB2, and BARD1
  • Environmental factors such as: cigarette smoking associated with mucinous ovarian cancer, asbestos,Talc (Its association is controversial).
  • Other factors such as: Diet: dairy food with high animal fat intake is claimed to be associated with ovarian cancer but data are not sufficient to confirm this association, exercise: No clear evidence about the association between physical activity and breast cancer, and obesity: can increases the risk of ovarian cancer and the risk of its mortality, Pelvic inflammatory disease can increase the risk of and might be used as tumor marker for ovarian tumor

Known risk factors

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

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 tumors 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 cancer in the lining of the abdominal cavity. But there may be a more favorable 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.
• 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.

Nullipara

• 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 tumors 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 fibers 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 fibers which 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

• Endometriosis occurs when the lining of the uterus (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 tumors, 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.