Clear cell ovarian cancer

Oral contraceptive use provides clear, long-term protection against epithelial ovarian cancer, according to results from a Swedish case-control study. (1) Analyses contrasting 655 women with ovarian cancer and 3,899 controls revealed that ever-users of the pill have a substantially reduced risk of developing any type of invasive ovarian cancer compared with never-users (odds ratio, 0.7). Moreover, pill use protects against ovarian cancer for up to 25 years after use ceases. In contrast, women who have used hormone replacement therapy are at significantly increased risk of ovarian cancer (odds ratio, 1.4).

Swedish women aged 50-74 were recruited for the study between October 1993 and December 1995. A total of 914 women with any type of ovarian cancer, identified through regional cancer registries, agreed to participate in the research; data on 655 with epithelial ovarian cancer were used for the analysis. The 3,899 controls were identified from a population register of all Swedish residents. On average, cases and controls were 62-63 years of age, had reached menopause at approximately age 50, had had two births, had been about 25 years of age at first birth and 30 at last birth, and had breastfed for around 10-11 months.

Thirty-two percent of women with cancer and 35% of controls had ever used oral contraceptives, while 26% and 21%, respectively, had ever used hormone replacement therapy (estrogen with or without progestin). Twelve percent of cases and 10% of controls had a family history of breast cancer; 6% and 3%, respectively, had a family history of ovarian cancer. Nineteen percent of those with cancer and 11% of controls had never given birth.

Women who had ever used the pill were at significantly reduced risk of epithelial ovarian cancer (odds ratio, 0.7). When the researchers conducted separate analyses by type of ovarian tumor, they found comparably reduced odds for the two most common ones (serous and endometrioid). However, the risk of developing a mucinous ovarian tumor (a type that constituted about 9% of all ovarian cancer cases) was significantly elevated among pill users, relative to nonusers (odds ratio, 2.0).

Duration of pill use was associated with the occurrence of ovarian cancer: The odds of developing epithelial ovarian cancer were not significantly affected among women who had used the pill for fewer than five years. However, these odds were substantially reduced among women who had used the pill for 5-9 years (0.5) or for 10 or more years (0.4).

The protective effect of past oral contraceptive use was evident for up to 25 years following cessation of use: Overall odds ratios were significantly reduced among women who had stopped using the pill fewer than 15 years before the study (odds ratio, 0.5), 15-19 years before (0.7) or 20-24 years before (0.7).

For women who had used hormone replacement therapy, the overall risk of epithelial ovarian cancer was elevated (odds ratio, 1.4), as were the risks of developing the two most common types of ovarian tumors, serous (1.5) and endometrioid (1.4). Ovarian cancer risk was most elevated among women who had used replacement hormones for 10 or more years (odds ratio, 2.0). However, there was no association between the recency of hormone replacement therapy and the risk of ovarian cancer.

Reproductive factors beside hormone exposure had a substantial impact on women's likelihood of developing epithelial ovarian cancer. The analyses confirmed the consistent protective effect of childbearing. The likelihood of developing ovarian cancer fell as women's number of births increased (odds ratios declined from 0.6 among women who had had one birth to 0.3 among those who had had five or more). In contrast, age at first birth was associated with the risk of ovarian cancer only among women who first delivered at age 35 or older (0.5). Duration of breastfeeding did not affect the overall risk of epithelial ovarian cancer, although the risk of clear-cell carcinoma (a relatively rare type of ovarian tumor) was substantially reduced among women who breastfed for at least six months (0.2).

There were no significant associations between cancer risk and women's age at menarche. However, women who reached menopause before age 49 were significantly less likely than those who did so at ages 49-52 to develop epithelial ovarian cancer (0.8). Women who had had irregular menstrual cycles were marginally more likely to develop ovarian cancer than were those who had not (1.2), and were significantly more likely to develop an endometrioid ovarian tumor (1.6).

Finally, as might be expected, one of the strongest factors in the incidence of ovarian cancer was a family history of it: Women whose mother or sister had had ovarian cancer were substantially more likely than other women to have developed any type of epithelial ovarian cancer (2.9). Such women also had a significantly elevated risk of serous (3.8) and endometrioid (2.9) cancers.

The investigators observe that while the causes of ovarian cancer have never been determined, a number of hypotheses have been advanced--incessant ovulation, high levels of circulating gonadotropins, ovarian exposure to contaminants via the fallopian tubes and low progesterone levels. They argue that their results, and those of other investigators, suggest that exposure to contaminants "seems compatible with most established epidemiologic associations."

REFERENCE

(1.) Riman T et al., Risk factors for invasive ovarian cancer: results from a Swedish case-control study, American Journal of Epidemiology, 2002, 156(4):363-373.