17.3 Risk factors

Table 17.2 Risk factors for ovarian cancer, by direction of association and strength of evidence


Increases risk

Decreases risk

Convincing or probable

Family history of ovarian cancer1,2

Tubal ligation13 or hysterectomy with ovarian conservation11,14



Oral contraceptives6,15,16,17


Hormone replacement therapy4,5,6




Tobacco smoking8,9




Fertility drugs3,11

Breast feeding18

Greater body fatness7,12

Non-starchy vegetables19,20

Physical activity21

1 one or more first degree relative(s) with cancer of the ovary; 2 Stratton et al., 1998; 3 Ness et al., 2002; 4 particularly oestrogen-only formulations; 5 Pearce et al., 2009; 6 International Agency for Research on Cancer, 2011a; 7 Schouten et al., 2008; 8 associated with mucinous tumours only; 9 Secretan et al., 2009; 10 Straif et al., 2009; 11 Whittemore et al., 1992; 12 Lahmann et al., 2010;

13 surgical procedure involving cutting or blocking a woman’s fallopian tubes; 14 Cibula et al., 2011; 15 combined oestrogen-progestogen formulations; 16 Collaborative Group, 2008; 17 Cibula et al., 2010; 18 Ip et al., 2009; 19 includes broccoli, cabbage, carrots, cauliflower, celery, leeks, lettuce, onions, peas, peppers and spinach; 20 World Cancer Research Fund / American Institute of Cancer Research, 2007; 21 Olsen et al., 2007

Family history of the disease is the most important risk factor for ovarian cancer. Women with at least one affected first degree relative have a three-fold increased risk of developing ovarian cancer themselves. Together with breast cancer, ovarian cancer is a component of several autosomal dominant cancer syndromes, most notably the BRCA1 and BRCA2 mutation syndromes. Women who have mutations in the BRCA1 or BRCA2 genes have a high chance of developing ovarian cancer over their lifetime (39% risk for BRCA1 mutation carriers and 11% for BRCA2 mutation carriers up to the age of 70; Antoniou et al., 2003).

Endogenous and exogenous oestrogens play a key role in the aetiology of ovarian cancer. Not having children (nulliparity) is associated with increased risk and, by contrast, each additional child confers a 20% reduction in risk (Riman et al., 2004). Women who have used fertility drugs may also have raised risk, especially if they remain nulligravid. Risk is reduced in women who have had bilateral tubal ligation (their fallopian tubes “tied”) or hysterectomy with ovarian conservation. In terms of exogenous hormones, use of hormone replacement therapy, particularly oestrogen-only formulations, is clearly related to increased risk, although formulations which include progestin are associated with only a modest risk. Women who have used combined oestrogen-progestogen oral contraceptives have decreased risk. Protection increases with increasing duration of use, and the reduction in risk persists for more than 30 years after use has ceased. Breastfeeding has also been associated with lower risk of ovarian cancer, but uncertainties remain in the evidence.

Risk of ovarian cancer is raised in taller women, but tallness in itself is unlikely to be a causal factor; it is most likely a marker for factors relating to promoters of growth in childhood (World Cancer Research Fund / American Institute of Cancer Research, 2007).

Several lifestyle factors have been related to ovarian cancer risk, but most of the associations remain somewhat uncertain. The exception is smoking, which is causally related to mucinous ovarian tumours, but not to other tumour types (Jordan et al., 2006). Higher intake of non-starchy vegetables may be associated with reduced risk, but this category includes a wide and disparate group of vegetables with many different plant food constituents (e.g. fibre, folate, flavonoids) and the contributions of the different constituents have not been unravelled (World Cancer Research Fund / American Institute of Cancer Research, 2007). There may be a modest (approximately 20%) reduction in risk among women with the highest, versus those with the lowest, levels of recreational physical activity. Body fatness and/or obesity may also be related to increased risk.

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