Cancer Research UK : UK Ovarian Cancer risk factors

UK Ovarian Cancer risk factors

This section contains information on the risk factors of ovarian cancer including parity, breastfeeding, infertility, fertility treatment, oral contraceptives, tubal ligation, hormone replacement therapy (HRT), talc, body mass index and height (BMI), Ovarian cysts and endometriosis, medication usage, family history and smoking.

The causes of ovarian cancer are unknown, but several factors are considered to exert an influence over its development. The two most influential risk factors are increasing age (Figure 4.1) and the presence of certain gene mutations. Associations with other risk (and protective) factors are outlined below.

Figure 4.1: Numbers of new cases and age-specific incidence rates, ovarian cancer, UK, 2002

Download this chart (27.5KB)

Parity and ovarian cancer risk

The risk of ovarian cancer is lower in women that have had children compared to women who have no children. Risk reduces the more children a women has, and women that have no children have double the risk of women with three or more children, as shown in Table 4.1.53, 2.

Table 4.1: Risk ratios for risk of ovarian cancer by number of children

Download this table 20.0(KB)

Breastfeeding and ovarian cancer risk

There was an approximate 20% reduced risk of ovarian cancer in parous women who had ever breastfed compared to those who had never breastfed in one collaborative study2. However, other studies found an effect only in certain histological subtypes of ovarian cancer3, 4. The only prospective study to examine this issue showed a significant reduction in risk for women breastfeeding for 18 months or longer.32 Thus, although some uncertainty remains, the evidence suggests breastfeeding may be protective.

Infertility and ovarian cancer risk

A recent pooled analysis of eight case-control studies investigating the relationship between infertility and ovarian cancer reported that nulligravid women who had been attempting pregnancy for more than five years had an increased odds ratio of 2.67 (95%CI 1.91 to 3.74) compared to women who had been trying to conceive for less than a year1.

Fertility treatment and ovarian cancer risk

The evidence does not support a link between fertility treatments and risk of ovarian cancer.1, 33

Oral contraceptives and ovarian cancer risk

The use of oral contraceptives is protective, perhaps due to cessation of ovulation. A recent collaborative analysis of six case-control studies, using data from 2,768 incident cases and 6,274 hospital controls, showed a significant reduction in ovarian cancer risk in ever versus never users (odds ratio 0.66, 95%CI 0.56 to 0.79). This protective effect of the oral contraceptive pill appeared to be prolonged, with no significant differences between women who discontinued use within the last 10 years compared to those who ceased use over 20 years ago.6, 34

There is a larger effect in long-term users (five years or longer) than in those with shorter duration of use (under five years) (odds ratio 0.5, 95%CI 0.33 to 0.76) 6.

Tubal ligation and ovarian cancer risk

Tubal ligation has a protective effect on ovarian cancer with an estimated reduced risk of between 18% and 70%7, 8,35. Hysterectomy may also reduce risk8.

Hormone replacement therapy (HRT) and ovarian cancer risk

Ever use of hormone replacement therapy (HRT) is associated with a 19-24% increase in risk of ovarian cancer, according to the most recent meta-analysis. The results support a greater risk of oestrogen-only therapy compared to oestrogen-progestin therapy.36 Risk is not increased in women using HRT for less than five years and reduces once a woman stops taking it.47

Talc and ovarian cancer risk

Several epidemiological studies have reported an association between ovarian cancer and perineal talc application (talc is a mineral compound that consists of magnesium silicate and is the principal component in baby powder and cosmetic talcum powders). However, many of the studies were small and no consistent relationship between talcum powder usage and increased risk of ovarian cancer has been reported.

A systematic review has been conducted to attempt to clarify the evidence regarding this potential risk factor. Sixteen papers contributed data to the meta-analysis (a total of 11,933 subjects from 15 case control studies and one cohort study). Overall results showed a statistically significant increased risk associated with talc use, RR = 1.33 (95%CI 1.16 to 1.45). However, further inspection of the data failed to show any clear relationship between dose and response, and therefore the authors of the review concluded that this association is likely to be spurious and due to uncontrolled confounding or selection biases13. Since then, a combined analysis of two case-control studies showed a RR of 1.36 (95%CI 1.14 to 1.63) for regular talc use, and a significant trend of increasing risk with more frequent use.37 A third case-control study reported an OR of 1.17 (95%CI 1.01 to 1.36) for ovarian cancer for women who reported perineal use of talcum powder and a significant trend with years of use.49

Body mass index (BMI) and height and ovarian cancer risk

The International Agency for Research in Cancer (IARC) was unable to draw a conclusion on a possible association between body mass index (BMI) and ovarian cancer because the published studies were inconsistent in their results17. A meta-analysis of prospective studies published since the IARC review showed that pre-menopausal women with a BMI of 30 or above have a RR of 1.72 (95%CI 1.02-2.89) compared to lean women, but there is no effect of BMI on risk in post-menopausal women.18. This study also showed that taller women have an increased risk of pre-menopausal and post-menopausal ovarian cancer, with relative risks of 1.79 (95%CI 1.07 to 3) and 1.25 (95%CI 1.04 to 1.49), respectively.

Ovarian cysts and endometriosis and ovarian cancer risk

Polycystic ovary syndrome is a common endocrine disturbance affecting women of reproductive age, which is linked to an increased risk of endometrial cancer.48 Limited research has been conducted into the relationship between PCOS and ovarian cancer and further investigation is needed22, 23. A large study linking records of women with ovarian cysts to cancer registry data showed that women with a hospital discharge diagnosis of ovarian cysts before the age of 29 had a higher risk of ovarian cancer, with a RR of 2.2 (95%CI 1.3 to 3.9), and women who had surgical resection of cysts or a unilateral oophorectomy as treatment had a RR of 8.8 (95%CI 5.2 to 15). This study also showed that women with a hospital discharge diagnosis of endometriosis had a RR of 1.34 (95%CI 1.03 to 1.75) for ovarian cancer.42

Medication usage and ovarian cancer risk

A meta-analysis did not provide evidence that use of aspirin or non-aspirin anti-inflammatory drugs reduce risk of ovarian cancer.30 A meta-analysis of paracetamol specifically provided some evidence that regular use reduces risk (RR 0.7, 95%CI 0.51 to 0.95).31. Since these studies, findings have been inconsistent.49-52

Family history and previous cancers and ovarian cancer risk

On average, women with a mother or sister diagnosed with ovarian cancer have a RR of 2.6 (95%CI 2.2 to 3.08) for ovarian cancer.53 BRCA1 and BRCA2 mutations are known to increase the risk of ovarian cancer, with cumulative risks of developing ovarian cancer by the age of 70 among carriers of 40% (95% CI 35% to 46%) and 18% (95%CI 13% to 23%), respectively.43 However, only about one in ten ovarian cancer cases occur in patients with a BRCA1 or 2 mutation or other genetic mutation known to predispose to the disease.44 Women with a previous breast cancer have a doubled risk of ovarian cancer, and the risk is almost four-fold for women diagnosed with breast cancer before the age of 40. Risk in former breast cancer patients with a family history of breast or ovarian cancer is even higher.45

Smoking and ovarian cancer risk

A meta-analysis showed a RR of 2.1 (95%CI 1.7 to 2.7) for mucinous ovarian tumours in current smokers. On the other hand, the same analysis showed a reduction in risk of clear cell cancers in current smokers, with a RR of 0.6 (95%CI 0.3 to 0.9).46

References for ovarian cancer risk factors

Ness, R.B., et al., Infertility, fertility drugs, and ovarian cancer: a pooled analysis of case-control studies. Am J Epidemiol, 2002. 155(3): p. 217-24.
Whittemore, A., et al., Characteristics relating to ovarian cancer risk: Collaborative analysis of 12 US case-control studies. American Journal of Epidemiology, 1992. 136 (10): p. 1184-1203.
Riman, T., et al., Risk factors for invasive epithelial ovarian cancer: results from a Swedish case-control study. Am J Epidemiol, 2002. 156(4): p. 363-73.
Siskind, V., et al., Breastfeeding, menopause, and epithelial ovarian cancer. Epidemiology, 1997. 8(2): p. 188-91.
Riman, T., I. Persson, and S. Nilsson, Hormonal aspects of epithelial ovarian cancer: review of epidemiological evidence. Clin Endocrinol (Oxf), 1998. 49(6): p. 695-707.
Bosetti, C., et al., Long-term effects of oral contraceptives on ovarian cancer risk. Int J Cancer, 2002. 102(3): p. 262-5.
Green, A., et al., Tubal sterilisation, hysterectomy and decreased risk of ovarian cancer. Survey of Women's Health Study Group. Int J Cancer, 1997. 71(6): p. 948-51.
Hankinson, S.E., et al., Tubal ligation, hysterectomy, and risk of ovarian cancer. A prospective study. JAMA, 1993. 270(23): p. 2813-8.
Garg, P.P., et al., Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis. Obstet Gynecol, 1998. 92(3): p. 472-9.
Coughlin, S.S., et al., A meta-analysis of estrogen replacement therapy and risk of epithelial ovarian cancer. J Clin Epidemiol, 2000. 53(4): p. 367-75.
Rodriguez, C., et al., Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. JAMA, 2001. 285(11): p. 1460-5.
Anderson, G.L., et al., Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. JAMA, 2003. 290(13): p. 1739-48.
Huncharek, M., J.F. Geschwind, and B. Kupelnick, Perineal application of cosmetic talc and risk of invasive epithelial ovarian cancer: a meta-analysis of 11,933 subjects from sixteen observational studies. Anticancer Res, 2003. 23(2C): p. 1955-60.
Huncharek, M., H. Klassen, and B. Kupelnick, Dietary beta-carotene intake and the risk of epithelial ovarian cancer: a meta-analysis of 3,782 subjects from five observational studies. In Vivo, 2001. 15(4): p. 339-43.
Huncharek, M. and B. Kupelnick, Dietary fat intake and risk of epithelial ovarian cancer: a meta-analysis of 6,689 subjects from 8 observational studies. Nutr Cancer, 2001. 40(2): p. 87-91.
Koushik, A., et al., Intake of the major carotenoids and the risk of epithelial ovarian cancer in a pooled analysis of 10 cohort studies. Int J Cancer, 2006. 119(9): p. 2148-54.
International Agency for Research on Cancer, IARC Handbooks of Cancer Prevention: Weight Control and Physical Activity, ed. H. Vaino and F. Bianchini. Vol. 6. 2002, Lyon: IARC Press.
Schouten, L.J., et al., Height, body mass index, and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol Biomarkers Prev, 2008. 17(4): p. 902-12.
Calle, E.E., et al., Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med, 2003. 348(17): p. 1625-38.
Purdie, D.M., et al., Body size and ovarian cancer: case-control study and systematic review (Australia). Cancer Causes Control, 2001. 12(9): p. 855-63.
Lubin, F., et al., Body mass index at age 18 years and during adult life and ovarian cancer risk. Am J Epidemiol, 2003. 157(2): p. 113-20.
Solomon, C.G., The epidemiology of polycystic ovary syndrome. Prevalence and associated disease risks. Endocrinol Metab Clin North Am, 1999. 28(2): p. 247-63.
Schildkraut, J.M., et al., Epithelial ovarian cancer risk among women with polycystic ovary syndrome. Obstet Gynecol, 1996. 88(4 Pt 1): p. 554-9.
Ness, R., et al., Serologic evidence of past infection with Chlamydia trachomatis in relation to ovarian cancer. Journal of Infectious Diseases, 2003. 187: p. 1147-1152.
Parazzini, F., et al., Pelvic inflammatory disease and risk of ovarian cancer. Cancer Epidemiology Biomarkers and Prevention, 1996. 5 (8): p. 667-669.
Risch, H. and G. Howe, Pelvic inflammatory disease and the risk of epithelial ovarian cancer. Cancer Epidemiology Biomarkers and Prevention, 1995. 4 (5): p. 447-451.
Ip, S.M., et al., Detection of human papillomavirus DNA in malignant lesions from Chinese women with carcinomas of the upper genital tract. Gynecol Oncol, 2002. 87(1): p. 104-11.
Wu, Q.J., et al., Detection of human papillomavirus-16 in ovarian malignancy. Br J Cancer, 2003. 89(4): p. 672-5.
Hisada, M., et al., Prospective study of antibody to human papilloma virus type 16 and risk of cervical, endometrial, and ovarian cancers (United States). Cancer Causes Control, 2001. 12(4): p. 335-41.
Bonovas, S., et al., Do nonsteroidal anti-inflammatory drugs affect the risk of developing ovarian cancer? A meta-analysis. Br J Clin Pharmacol, 2005. 60(2): p. 194-203.
Bonovas, S., et al., Paracetamol use and risk of ovarian cancer: a meta-analysis. Br J Clin Pharmacol, 2006. 62(1): p. 113-21.
Danforth, K.N., et al., Breastfeeding and risk of ovarian cancer in two prospective cohorts. Cancer Causes Control, 2007. 18(5): p. 517-23.
Kashyap, S., et al., Assisted reproductive technology and the incidence of ovarian cancer: a meta-analysis. Obstet Gynecol, 2004. 103(4): p. 785-94.
Collaborative Group on Epidemiological Studies of Ovarian Cancer Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls Lancet, 2008. 371(9609): p. 303-14.
Kjaer, S.K., et al., Tubal sterilization and risk of ovarian, endometrial and cervical cancer. A Danish population-based follow-up study of more than 65 000 sterilized women Int J Epidemiol, 2004. 33(3): p. 596-602.
Zhou, B., et al., Hormone replacement therapy and ovarian cancer risk: a meta-analysis Gynecol Oncol, 2008. 108(3): p. 641-51.
Gates, M.A., et al., Talc use, variants of the GSTM1, GSTT1, and NAT2 genes, and risk of epithelial ovarian cancer Cancer Epidemiol Biomarkers Prev, 2008. 17(9): p. 2436-44.
Genkinger, J.M., et al., A pooled analysis of 12 cohort studies of dietary fat, cholesterol and egg intake and ovarian cancer Cancer Causes Control, 2006. 17(3): p. 273-85.
Prentice, R.L., et al., Low-fat dietary pattern and cancer incidence in the Women's Health Initiative Dietary Modification Randomized Controlled Trial J Natl Cancer Inst, 2007. 99(20): p. 1534-43.
Genkinger, J.M., et al., Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies Cancer Epidemiol Biomarkers Prev, 2006. 15(2): p. 364-72.
Steevens, J., et al., Tea and coffee drinking and ovarian cancer risk: results from the Netherlands Cohort Study and a meta-analysis Br J Cancer, 2007. 97(9): p. 1291-4.
Borgfeldt, C., and Andolf, E., Cancer risk after hospital discharge diagnosis of benign ovarian cysts and endometriosis Acta Obstet Gynecol Scand, 2004. 83(4): p. 395-400.
Chen, S., and Parmigiani, G., Meta-analysis of BRCA1 and BRCA2 penetrance J Clin Oncol, 2007. 25(11): p. 1329-33.
Rubin, S.C., et al., BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing Am J Obstet Gynecol, 1998. 178(4): p. 670-7.
Bergfeldt, K., et al., Risk of ovarian cancer in breast-cancer patients with a family history of breast or ovarian cancer: a population-based cohort study Lancet, 2002. 360(9337): p. 891-4.
Jordan, S.J., et al., Does smoking increase risk of ovarian cancer? A systematic review Gynecol Oncol, 2006. 103(3): p. 1122-9.
Beral, V., et al., Ovarian cancer and hormone replacement therapy in the Million Women Study Lancet, 2007. 369(9574): p. 1703-10.
Norman, R.J., et al., Polycystic ovary syndrome Lancet, 2007. 370(9588): p. 685-97.
Merritt, M.A., et al., Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer Int J Cancer, 2007. 122: p. 170-76.
Wernli, K.J., et al., Inverse association of NSAID use and ovarian cancer in relation to oral contraceptive use and parity Br J Cancer, 2008. 98(11): p. 1781-3.
Schildkraut, J.M., et al., Analgesic drug use and risk of ovarian cancer Epidemiology, 2006. 17(1): p. 104-7.
Hannibal, C.G., et al., Analgesic drug use and risk of epithelial ovarian cancer Am J Epidemiol, 2008. 167(12): p. 1430-7.
Granstrom, C., et al., Population attributable fractions for ovarian cancer in Swedish women by morphological type Br J Cancer, 2008. 98(1): p. 199-205.

Next section - Molecular Biology and Genetics