Characteristics Relating to Ovarian Cancer Risk: Collaborative Analysis of 12 US Case -Control Studies

Abstract

Data collected from 2,197 white ovarian cancer patients and 8,893 white controls in 12 US case-control studies conducted in the period 1956-1986 were used to evaluate the relation of invasive epithelial ovarian cancer to reproductive and menstrual characteristics, exogenous estrogen use, and prior pelvic surgeries. Clear trends of decreasing risk were evident with increasing number of pregnancies (regardless of outcome) and increasing duration of breast feeding and oral contraceptive use. Ovarian dysfunction leading to both infertility and malignancy is an unlikely explanation for these trends for several reasons: 1) The trends were evident even among the highly parous; 2) risk among nulliparous women did not vary by marital status or gravidity; and 3) risk among ever-married women showed little relation to length of longest pregnancy attempt or history of clinically diagnosed infertility. Risk was increased among women who had used fertility drugs and among women with long total duration of premenopausal sexual activity without birth control; these associations were particularly strong among the nulligravid. No consistent trends in risk were seen with age at menarche, age at menopause, or duration of estrogen replacement therapy. A history of tubal ligation or of hysterectomy with ovarian conservation was associated with reduced ovarian cancer risk. These observations suggest that pregnancy, breast feeding, and oral contraceptive use induce biological changes that protect against ovarian malignancy, that, at most, a small fraction of the excess ovarian cancer risk among nulliparous women is due to infertility, and that any increased risk associated with infertility may be due to the use of fertility drugs.

Mechanisms Regulating the Constitutive Activation of the Extracellular Signal-Regulated Kinase (ERK) Signaling Pathway in Ovarian Cancer and the Effect of Ribonucleic Acid Interference for ERK1/2 on Cancer Cell Proliferation

“…O VARIAN CANCER IS the fifth most commonly diagnosed cancer among United States women and the most frequent cause of death from gynecological malignancy, accounting for 14,500 deaths yearly (1,2). In 75% of new cases, the cancer has spread beyond the ovary at the time of detection and the 5-yr survival in these patients is less than 35% (3).…”

BRCA1 and BRCA2 Mutations in the Ovarian Cancer Population across Race and Ethnicity: Special Reference to Asia

“…The risk factors for the development of ovarian carcinoma include nulliparity, infertility and a history of breast cancer [4,5,6,7,8,9]. The strongest risk factor for ovarian cancer is a positive family history of breast and/or ovarian cancer as reported in approximately 5–15% of ovarian cancer cases.…”

Use of fertility drugs and risk of ovarian cancer

“…In the 1990s, several epidemiological studies, including a meta-analysis of 12 case-control studies, reported an association between use of fertility drugs and the development of ovarian cancer [26–28]. These publications raised substantial concern regarding the safety of ovulation-inducing drugs and prompted multiple other investigations.…”

“…However, concern regarding potential side effects of fertility drugs remained after other studies reported that women who were treated with fertility drugs for more than 12 cycles had an increased risk of ovarian cancer [35,36]. In addition, results from several of these earlier studies indicated that women who remained nulligravid after fertility treatment may be at increased risk for ovarian cancer and also that fertility drugs may preferentially increase the risk of borderline ovarian tumors [26–28,32,37–40]. Results from the few earlier studies that examined the relationship between IVF treatment and risk of ovarian cancer have been conflicting as well, with some reporting no link between IVF treatment and ovarian cancer risk [41–44], while others found an increased risk of ovarian cancer in IVF users [45–47*].…”