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last updated in 2004 

Ovarian Cancer is a Killer

Even though not common, ovarian cancer is the fifth leading cause of cancer deaths for women in the United States. Ovarian cancer is expected to cause 16,000 deaths in the U.S. in 2004 . It causes so many deaths in part because it is often not detected until a late stage.

Ovarian cancer strikes women living in the US, Canada, and Europe more frequently than in the rest of the world. In countries where ovarian cancer is more common, its incidence is fairly stable , but in countries where ovarian cancer is less common, its incidence is increasing.

The American Cancer Society estimates that about 25,580 new cases of ovarian cancer will be diagnosed in the United States during 2004. White women have a 50% greater risk of ovarian cancer compared to black women, in the U.S., although the reasons why are not fully understood.

What Causes Ovarian Cancer? Ovarian cancer is almost certainly caused by a combination of genetic, hormonal, and environmental factors.

• Hormonal Factors : Women who have not had children face a greater risk of ovarian cancer than do women who have borne children, and women with multiple pregnancies and who breast feed longer have a lower risk compared to those with one or no pregnancies or with little or no breast-feeding history. For example, a woman who has had three children is half as likely to develop ovarian cancer as a woman who has had no children. While women who take oral contraceptives for prolonged periods appear to have a lower risk of ovarian cancer, women that use hormone replacement therapy (HRT) in an estrogen-only form, or in a form where estrogen and then progestin are used in sequence, appear to have an increased risk of ovarian cancer.

• Inherited Factors : Having a mother or sister with ovarian cancer means your risk of ovarian cancer is greater compared to someone without this family history. Overall, family history is estimated to account for only 4-5 percent of cases of ovarian cancer.
• A small fraction of ovarian cancer has been linked to a gene mutation on the BRCA genes, called “the breast cancer genes.” Women with a mutation on one of the BRCA or breast cancer genes face a much higher risk of breast or ovarian cancer compared to women without this mutation.
• Women with one or more Jewish grandparents have more than double the odds of having ovarian cancer, compared to women without Jewish grandparents. This may be due to the higher prevalence of the BRCA or breast cancer genes among Jewish women.
• Another gene important in metabolizing the hormone estrogen and in detoxifying many chemical carcinogens (such as those found in smoke and soot), called the CYP1A1 gene, can also affect one’s risk of ovarian cancer. Having a certain form of the CYP1A1 gene can increase one’s risk of ovarian cancer. For example, one study in Turkish women found that having a certain form of the CYP1A1 gene resulted in a six-fold greater risk of ovarian cancer. Another study in Hawaii looked at a similar gene and found that it resulted in a four-fold increase in the odds of ovarian cancer, in all ethnic groups studied.

 

• Environmental Factors : A number of different environmental factors are under investigation for their role in ovarian cancer, including solvents, dyes, organic dusts (paper dust, wood dust), triazine herbicides, and talc (when used in the genital area). Vitamin D may play a role in protecting against ovarian cancer. For most of these, the evidence is limited and their role is still uncertain.

Investigations into some of these environmental factors have been prompted by observations that women in certain occupations seem to have higher rates of ovarian cancer. For example, working in the graphics and printing industries is associated with an increased risk of ovarian cancer, suggesting that solvents used in those industries might be involved. Studies linking work in the telephone industry with an increased risk of ovarian cancer have raised questions about electromagnetic field (EMF) exposures.

A large Swedish study has suggested that women who work in the paper and packaging industry, the lumber and carpentry industry, and the textile and shoe industry, may also be at increased risk of ovarian cancer. Carcinogenic dyes are used in the shoe, graphics, and textile industries, and these may be responsible. The same Swedish study did not find any association between ovarian cancer and exposure to solvents, pesticides, electromagnetic fields, sunlight, and physical activity. Most studies suggest a slight increase in risk of ovarian cancer in women who used talc on the genital area.

Why are ovarian cancer rates different in different countries?

Ovarian cancer occurs more often in industrialized countries except Japan. For example, in St. Gall, Switzerland, the incidence of ovarian cancer is 17 times that in Bamako, Borneo. It isn’t clear whether these geographical differences are due to genetic differences, environmental factors, differences in reproduction patterns, or some combination of these. One study found that when Japanese women move to the United States to live, the occurrence of ovarian cancer in their daughters increased to be closer to the occurrence in the United States – suggesting that environmental factors, more than genetic factors, probably account for the differences between countries. Another study found no difference between Asian Americans born in Asia and those born in America with respect to their risk of ovarian cancer.

Researchers are investigating whether the difference might be related to sunlight and vitamin D. Countries where ovarian cancer are lower –countries in Africa, and South America—are sunnier than those where ovarian cancer is higher—countries in North America, and northern and central Europe. Vitamin D is naturally produced in the skin in sunlight, and has anti-cancer properties. A number of studies lend weight to this hypothesis.

Another possibility is that genetics and the environment interact together to influence ovarian cancer risk. The gene CYP1A1 may be an important clue in understanding how our genes interact with environmental factors to influence cancer risk. This gene is important both in how the body processes or metabolizes estrogen, and in detoxifying certain chemical carcinogens. Some forms of the CYP1A1 gene are linked to an increased risk of ovarian cancer, as mentioned above, and are more common in different racial and ethnic groups. The gene can be passed down in families and may make people more susceptible to carcinogens.

Where does this leave us now?

A combination of genetic, hormonal, and environmental factors are important in causing ovarian cancer. The changes in DNA that cause normal ovarian cells to become cancerous are more likely to be acquired during a woman’s life rather than having been inherited, meaning that environmental factors are very important.

• The available scientific evidence does not prove definitively which environmental factors are involved in the causation of ovarian cancer.
• Since hormonal factors are important in ovarian cancer, one hypothesis is that chemicals that mimic or otherwise interfere with hormones may increase the risk the ovarian cancer. Some chemicals that disrupt hormonal systems, such as dioxin and the herbicide atrazine may cause or at least promote ovarian cancer in women based on evidence in animals.
• Prevention and early detection are key, in particular for those who may be at high risk. Ashkenazi Jewish women (Jewish women of Eastern European or German descent) should consider testing to see if they carry the BRCA1 or BRCA2 genes so that they can make more informed choices on how best to limit their cancer risk—which could include exercise, diet, removal of ovaries, family planning decisions, career and other choices that reduce exposures to agents that cause or are suspected of causing cancer, or a combination of these.
• Clearly, more research is needed to confirm and better understand geographical and occupational differences in ovarian cancer risks and rates and which environmental factors cause ovarian cancer.

For more details, read CHE's peer-reviewed analysis of environmental links to ovarian cancer.