Fact Sheets

Ovarian Cancer

Issue: The etiology of ovarian cancer is poorly understood; however, evidence of a possible relationship between environmental exposures and the risk of ovarian cancer does exist.

Background: Ovarian cancer is both the fifth most diagnosed cancer (accounting for 4% of all new cancers) and the fifth leading cause of cancer deaths (accounting for almost 5%) among Canadian women. Our knowledge of the risk factors for ovarian cancer is mainly related to hormonal and reproductive factors, including nulliparity, late age at menopause, family history of ovarian and breast cancer, and infrequent oral contraceptive use. Epidemiologic studies, animal experiments, and receptor binding studies suggest that malignant ovarian tumors may be endocrine related and hormone dependent. The hormone-dependency of ovarian cancer has led to the hypothesis that exogenous estrogenic compounds may play a role in the etiology of this cancer. Pesticides with endocrine disrupting activity remain legally or illegally in use in different countries, including organochlorine, organophosphorous, arsenic and mercury compounds, phenoxy acid herbicides, atrazine and dithiocarbamates. Scientific research to date suggests a link between atrazine and ovarian cancer.

Trends: Incidence and mortality rates for ovarian cancer have been relatively stable over time, though a modest decline in mortality has been observed. With approximately 2,600 new cases and 1,500 deaths annually, ovarian cancer is the leading cause of death from all gynecologic malignancies in Canada. The disease affects elderly and middle aged women with the highest incidence rates reported in North America and Northern Europe. Over the past 40 years, the rate of ovarian cancer mortality has increased among women aged 65 years and older. The incidence of ovarian cancer increases with age; it is relatively rare in women younger than 30 year of age, with only 1.5/100,000 women diagnosed annually in the 20-30 year age group, and 49/100,000 women diagnosed annually in the 60-69 year age group.

Consistency of the data: The etiology of ovarian cancer is largely unknown. Most established risk factors for the disease relate to reproductive events. Several case-control studies have found a decrease in risk of the epithelial ovarian cancer associated with pregnancy, breast feeding, and use of oral contraceptives (OCs). This prompted the hypothesis of incessant ovulation, which holds that factors which suppress ovulation may reduce the risk of developing ovarian cancer (Franceschi 1989). In a multicenter population-based, case-control study, the estimated relative risk of epithelial ovarian cancer was 0.5 (95% confidence interval 0.5 to 0.7) for women who had ever used oral contraceptives. The estimated risk reduction that occurred with oral contraceptives was 34% with any use, and this reduction increased to 70% with use for 6 or more years. However, several investigators have hypothesized that exposure to environmental toxicants such as pesticides and herbicides can be linked to ovarian cancer. Ovarian cancer has been linked with triazine herbicide exposure in a number of studies. In a case-control study by Donna (1989), women with previous exposure to triazine herbicides showed a two to threefold risk of epithelial ovarian cancer as compared to unexposed women. An association between atrazine and ovarian tumors has been observed in two Italian studies (Donna et al., 1984, 1989). However, two epidemiologic studies have suggested that atrazine may be carcinogenic to humans. Aside from phenoxy acid herbicides, atrazine is the most commonly used herbicide worldwide (Short & Colborn, 1999) and is used in the cultivation of corn, fruits, vegetables and grapes for producing wine. Atrazine has been classified as a possible human carcinogen by the International Agency on Cancer (IARC 1999).

Experimental evidence: A study by Wetzel et al. demonstrated that feeding Sprague-Dawley rats with a high dose of atrazine lengthened their estrus cycle, increased the number of days in estrus, and given in conjunction with estrogen, induced an earlier onset of mammary tumors (Wetzel et al., 1994). Atrazine is a genotoxic compound which induces DNA damage in some cells and increases mammary tumors in rats (but not in mice) treated orally.

Biological plausibility: The causes of ovarian cancer are poorly understood; however, a number of risk factors have been associated with either an increased or decreased likelihood of developing the disease. Epidemiologic studies, animal experiments, and receptor binding studies indicate that both normal ovaries and many malignant ovarian tumors are endocrine related and hormone dependent. The association between ovarian cancer and endogenous or hormonally related events has led to the hypothesis that exposure to exogenous compounds in the environment may increase the risk of this cancer.

Conclusion: Taken together, the evidence of an association between ovarian cancer and environmental toxins is limited, but remains an important issue to consider in future studies of this cancer.