19.3 Risk factors

Table 19.2 Risk factors for uterine cancer, by direction of association and strength of evidence

Increases risk

Decreases risk

Convincing or probable

Hormone replacement therapy1,2

Oral contraceptives2,18

 

Tamoxifen2

Physical activity4

 

Nulliparity3

 

Greater body fatness/abdominal fatness4,5

 

Diabetes6,7

 

Lynch syndrome (hereditary nonpolyposis colorectal cancer (HNPCC))8,9

 

Family history of cancer of the corpus uteri10,11,12

Possible

Early menarche13

Breast feeding19,20

Late natural menopause13

Non-starchy vegetables4,21

Polycystic ovary syndrome14

Soya or soya food products22,23

Red meat4,15

Foods containing fibre24

Diet with a high glycaemia load16,17

 

1 oestrogen-only formulations, and oestrogen-progestogen formulations where the progestogen is taken less than 15 days in the month; 2 International Agency for Research on Cancer, 2011a; 3 Dossus et al., 2010; 4 World Cancer Research Fund / American Institute of Cancer Research, 2007; 5 Crosbie et al., 2010 ; 6 Friberg et al., 2007; 7 Noto et al., 2010; 8 Bonadona et al., 2011;

9 Baglietto et al., 2010; 10 one or more first degree relative(s) with cancer of the corpus uteri; 11 Hemminki et al., 2005; 12 Lucenteforte et al., 2009; 13 Purdie and Green, 2001; 14 Jakimiuk and Issat, 2009; 15 includes beef, pork and lamb ; 16 glycaemic load is a ranking system for carbohydrate quantity and quality of food portions; 17 Mulholland et al., 2008; 18 combined oestrogen-progestogen pills; 19 Salazar-Martinez et al., 1999; 20 Newcomb & Trentham-Dietz, 2000; 21 includes broccoli, cabbage, carrots, cauliflower, celery, leeks, lettuce, onions, peas, peppers and spinach; 22 includes soya beans, edamame, tofu, soya milk; 23 Myung et al., 2009; 24 Bandera et al., 2007

Hormones play a major role in the aetiology of uterine cancer. A surge in incidence of these cancers in the USA in the late-1960s and mid-1970s led to the discovery of the role of hormone replacement therapy (Jick et al., 1980). Oestrogen-only formulations of hormone replacement therapy are now considered to be a causal agent and risk is also increased in women who use regimes which contain both oestrogen and progestogen, but in which the progestogen is taken for less than 15 days per month. Tamoxifen, a selective oestrogen receptor modulator used in the prevention and treatment of breast cancer, also causes uterine cancer. In contrast, use of combined oestrogen-progestogen oral contraceptives is protective. Risk is reduced by about half in women who have taken oral contraceptives, and the protective effect lasts for around two decades after cessation of use. However, it should be noted that these findings have generally been based on older high-dose oral contraceptives. In addition, reproductive factors associated with increased exposure to endogenous oestrogens may also influence risk. Women who have not had children (nulliparous) are at increased risk, while risk reduces with increasing number of full-term pregnancies. Risk may be raised in women with early menarche and late menopause, while breastfeeding may be protective. The strong and consistent association between body fatness and uterine cancer (60% increase in risk per 5 kg/m2 increase in body mass index) may also operate through effects on oestrogens and other hormones, such as insulin (World Cancer Research Fund / American Institute of Cancer Research, 2007). These effects are also a possible explanation for the observed relationship between higher levels of physical activity and reduced disease risk. As regards insulin levels more directly, there is a two to three-fold increased risk in diabetic individuals (both type 1 and type 2 diabetes).

Women who have one or more first-degree relatives affected by uterine cancer have a two-fold increased risk of developing the disease. Part of this is due to women in families affected by hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, also known as Lynch syndrome. Depending on which genetic mutations they carry, these women have a 20-55% chance of developing uterine cancer in their lifetime.

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