En. Meilahn et al., DO URINARY ESTROGEN METABOLITES PREDICT BREAST-CANCER - GUERNSEY-III COHORT FOLLOW-UP, British Journal of Cancer, 78(9), 1998, pp. 1250-1255
This is the first prospective study of urinary measures of the two maj
or competing pathways of oestrogen metabolism, 16 alpha-hydroxyoestron
e (16 alpha-OHE1) and 2-hydroxyoestrone (2-OHE1), in relation to incid
ent breast cancer risk, Experimental and case-control study results su
ggest that metabolism favouring the more oestrogenic 16 alpha-OHE1 pat
hway may be linked to higher breast cancer risk. Women aged 35 and old
er from Guernsey (n = 5104) were surveyed in 1977-85 and have been con
tinuously monitored for breast cancer and mortality up to the present
(Guernsey ill, Imperial Cancer Research Fund). Incident cases of breas
t cancer were matched to three control subjects for comparison of urin
ary oestrogen metabolite levels measured by enzyme immunoassay (EIA) i
n spot urine samples collected at baseline and stored frozen for up to
19 years. Consistent with case-control study results, post-menopausal
(but not premenopausal) women at baseline who went on to develop brea
st cancer showed about a 15% lower 2:16 alpha-OHE1 ratio than matched
control subjects. Further, subjects with metabolite ratios in the high
est tertile of 2:16 alpha-OHE1 had about a 30% lower risk than women w
ith ratios in the lowest two-thirds, although results were not statist
ically significant (OR = 0.71, 95% CI = 0.29-1.75). It is of potential
importance that, in contrast to most risk factors for breast cancer,
such as late age at first birth, oestrogen metabolism appears to be mo
difiable via diet and exercise, offering women the possibility of lowe
ring breast cancer risk through non-pharmacological measures, although
this remains to be tested.