Table 5 Possible pathways underlying growth–breast cancer associations (adapted from Okasha et al., 2002)

From: Associations of adult measures of childhood growth with breast cancer: findings from the British Women's Heart and Health Study

Growth as a biomarker for other exposures that influence breast cancer risk

1. In utero exposures

 Foetal nutrition is influenced by maternal steroids with greater exposure resulting in greater foetal growth

 Exposure to maternal steroids during breast development in utero may increase cancer risk

2. Infections

 Chronic infection may stunt growth – in particular trunk length

 Absence of childhood infection may make individuals susceptible to infections, which if acquired in later life are associated with cancer risk and may result in an underdeveloped immune function

3. Calorie intake

 Lower calorie intake in childhood results in shorter stature and in particular shorter leg length

 Lower incidence of cancer in rats fed a calorie-restricted diet

 Childhood calorie intake may be related to adult cancer

 Calorie intake may also influence growth-promoting hormones (see below)

Growth as a biomarker for biological mediators of risk

4. Cellularity

 Greater trunk length may reflect a larger number of breast cells

 A larger number of cells increases the risk that one will undergo malignant transformation

5. Growth-promoting hormones

 IGF is related to growth, particularly leg length

 IGF is affected by nutritional intake during childhood

 IGF is associated with cancer in animal studies although results from epidemiological studies are inconsistent

6. Oestrogen

 Low lifetime exposure to oestrogen will result in shorter trunk length because of osteoporotic collapse

 Later age at menarche will result in greater leg length and total height and may be associated with reduced lifetime exposure to oestrogen

 Breast cancer risk is associated with increased exposure to oestrogen

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