Multiple Risk Factors Are Associated with the Development of Ovarian Cancer

Multiple risk factors appear to play a role in the development of ovarian cancer (OC), the most fatal of the gynecologic cancers affecting primarily postmenopausal women. These factors fall broadly under reproductive history, lifestyle and exposure factors, and genetic/epigenetic factors. Mutations of BRCA1, BRCA2, and TP53 have been associated with increased OC risk and disease progression.¹ Women with a BRCA1 mutation are estimated to have a 40% to 50% risk of OC development by 70 years of age and a 10% to 20% risk with a BRCA2 mutation.²

The number of lifetime menstrual cycles is a factor reflected through many studies of OC risk-associated reproductive history. The age of menarche and of menopause onset have both been shown to be risk factors in OC, with earlier onset of menarche (although in a minor capacity) and later onset of menopause increasing the risk of OC.³

Parity status is also thought to be a risk factor because of its menstrual cycle relationship in that each full-term pregnancy (beyond a first pregnancy) additionally decreases risk of OC.³ Similarly, breastfeeding has been related inversely to OC risk. A recent population-based case-control study found that breastfeeding was associated with a decreased epithelial OC risk and showed that an average of 3 or more months’ breastfeeding duration significantly decreased OC risk.⁴ The same study found that earlier age of first breastfeeding significantly decreased OC by 37% and that later ages of first breastfeeding were associated with a decrease in its conferred protective effect.⁴ Although it remains to be further clarified, medical interventions to increase fertility in the form of fertility drugs may increase the risk of OC.³

Similar to pregnancy’s protective effects, reproductive prevention (resulting in decreased menstrual cycling) such as surgical and oral methods of contraception have been found to decrease the risk of OC. Tubal ligation and salpingectomy have been associated with a 13% to more than 50% decreased risk of OC.³ Combined oral contraception is known to confer a 25% to 30% protection against OC, providing increased protection with prolonged use.3 Oral contraception is estimated to have prevented 200,000 cases of OC and 100,000 deaths globally and is expected to increase in rate of prevention to 30,000 OC cases per year.³

In addition to contraception, other types of medical interventions have been evaluated for a potential association with OC development. Since the reproductive system is hormonally regulated, hormone replacement therapy has been studied and found to increase OC risk by 50% for every 5 years of use, with the risk plateauing after discontinuance of hormone replacement therapy.³ Another category of medical intervention, analgesia, has been investigated for potential risk of OC. A recent prospective cohort study found that current low-dose aspirin was associated with a decreased OC risk, whereas standard aspirin dosing did not share the association.⁵ The same study found a significant association between long-term use (≥10 years) of nonaspirin, nonsteroidal anti-inflammatory drugs, and increased OC risk.⁵

Lifestyle factors have also been studied for their association with OC risk. Regarding diet, there may be some increase in the risk of OC with meat/fat consumption and some decrease of risk with greater fruit and vegetable consumption.³ There has been no compelling evidence of any association between alcohol consumption and OC risk, and smoking was found to increase risk of mucinous OC but not of other histologic types of OC.³ Finally, application of talcum powder to the genital region has been associated with increased risk of OC.⁶ Additional risk factors may be discovered and further characterized with continued research.

References

1. Chandra A, Pius C, Nabeel M, et al. Ovarian cancer: current status and strategies for improving therapeutic outcomes. Cancer Med. 2019 Sep 27.
2. Webb PM, Jordan SJ. Epidemiology of epithelial ovarian cancer. Best Pract Res Clin Obstet Gynaecol. 2017;41:3-14.
3. La Vecchia C. Ovarian cancer: epidemiology and risk factors. Eur J Cancer Prev. 2017;26(1):55-62.
4. Modugno F, Goughnour SL, Wallack D, et al. Breastfeeding factors and risk of epithelial ovarian cancer. Gynecol Oncol. 2019;153(1):116-122.
5. Barnard ME, Poole EM, Curhan GC, et al. Association of analgesic use with risk of ovarian cancer in the nurses' health studies. JAMA Oncol. 2018;4(12):1675-1682.
6. Taher M, Farhat N, Karyakina NA, et al. Critical review of the association between perineal use of talc powder and risk of ovarian cancer. Reprod Toxicol. 2019;90:88-101.