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Do urinary oestrogen metabolites predict breast cancer in Guernsey women
– Reported, January 23, 2012
Women aged 35 and older from Guemsey (n = 5104) were surveyed in 1977-85 and have been continuously monitored for breast cancer and mortality up to the present (Guemsey 1II, Imperial Cancer Research Fund). Incident cases of breast cancer were matched to three control subjects for comparison of urinary oestrogen metabolite levels measured by enzyme immunoassay (EIA) in 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 breast cancer showed about a 15% lower 2:16ct-OHE1 ratio than matched control subjects. Further,subjects with metabolite ratios in the highest tertile of 2:16a-OHE1 had about a 30/o lower risk than women with ratios in the lowest twothirds,although results were not statisticalty significant (OR = 0.71, 95% Cl = 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 modifiable via diet and exercise, offering women the possibility of lowering breast cancer risk through non-pharmacological measures, although this remains to be tested.
This is the first study to examine oestrogen metabolites wele before the onset of breast cancer: median follow-up time to diagnosis
was 9.5 years (quartile 1 = 6 years. quartile 3 = 13 years).Prospective studies have not included measures of oestrogen metabolism as they have been complicated and invasive. involving radiolabelled tracers. The development of a new assay now allows oestrogen metabolites to be measured on stored unrne specimens without the use of tracers. Substantial evidence shows oestrogen to be implicated in breast carcinogenesis. but mechanisms remain unclear. Experimental and case-control study results have shown that metabolism of oestrogen that favours the 1 6a-hydroxyoestrone (16a-OHE1) over the 2-hydroxyoestrone (2-OHEI) pathway may increase risk of breast tumours. To test this hypothesis they measured 2-OHE1 and l6a-0HE1 in stored urine from incident breast cancer cases and matched control subjects among participants in the island of Guemsey (Guemsey HI) population-based prospective study of breast cancer risk.
Women aged 35 and older livina in Guemsey participated in a population-based sun-ey on factors thought to be associated with breast cancer risk. Of the ageeligible women on the island. 31 % volunteered to be surveyed.The survey. conducted by the Imperial Cancer Research Fund (ICRF). included questionnaires. mammography and collection of urne samples. both early morning and 24 h. The ICRF provided breast cancer incidence and mortality sur eillance.
Follow-up of the Guernsey HIl cohort for vital status and incident breast cancer through May 1996 was over 94% complete. Of 146
women identified with incident breast cancer from the Guernsey Ell study follow-up, samples for 111 were shipped for metabolite measurement and 102 are included in the analyses. Samples for two cases were never collected, ten were not found in the frozen sample bank and the remaining 23 cases were not eligible for this study as they reported oophorectomy, use of oestrogen or unclassifiable
menopausal status at baseline. Of the shipped samples, eight cases were diagnosed within 6 months of baseline and were therefore
considered prevalent cases, and the urine sample from one case yielded undetectable 16a-OHE1. Of the total 333 control samples (three per case) shipped for measurement, ten had undetectable levels of 16a-OHEI and/or creatinine. In addition, 24 were matched to the eight (ineligible) prevalent cases and three were matched to the case with no measured ratio, resulting in total number of control subjects with measured metabolites and matched to eligible cases of 296 and a total of 323 with measured metabolites.
If women who metabolize oestrogen predominately via the C2-hydroxylation pathway have a reduced risk of breast cancer, then
risk may be altered favourably by promotion of health behaviours that increase oestrogen hydoxylation by this pathway. We were not
able to examine whether diet or exercise influenced the metabolite ratio as this information was not available for this Guernsey study
cohort: nor did we have complete information on cigarette smoking. although smoking does not appear to influence breast cancer risk (Baron et al. 1996) and. therefore. is not likely to have affected the observed risk estimates. C2-hydroxylation appears to be more inducible than the 16a-OHEI and to be increased by consumption of cruciferous vegetables and possibly by exercise.
This is in contrast to other risk factors for breast cancer such as age at first birth or serum oestrogen concentration, which are not
amenable to change via behavioural means. Thus, although longterm health effects of alteration of oestrogen pathways are
unknown, advice to exercise more and eat more vegetables may provide more than cardiovascular benefit for women: such
behavioral changes may also reduce their risk of breast cancer.
Credits: EN Meilahn, B De Stavolal, DS Allen, I Fentiman, HL Bradlow, DW Sepkovic and LH Kuller
More Information at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063014/pdf/brjcancer00013-0133.pdf
– WF Team