H. Adlercreutz et al., ESTROGEN METABOLISM AND EXCRETION IN ORIENTAL AND CAUCASIAN WOMEN, Journal of the National Cancer Institute, 86(14), 1994, pp. 1076-1082
Background: Caucasian and Oriental women have different incidence rate
s of breast cancer. Among the underlying risk factors for the developm
ent of breast cancer in the women of these two groups may be their dif
ferent diets and patterns of estrogen metabolism and excretion. The ab
solute levels and relative ratios of 16 alpha-hydroxylated estrogens a
nd 2-hydroxylated estrogens (catechol estrogens) in the body may have
a role in the etiology of breast cancer, but studies so far have provi
ded only conflicting results. Purpose: Our goal was to study estrogen
metabolism, in particular, the extent of 2-hydroxylation and 16 alpha-
hydroxylation of estrogens in two groups of women, one Caucasian and o
ne Oriental, with inherently different breast cancer risks. Methods: D
ietary records were analyzed over 3-day periods in the midfollicular p
hase, twice, at 6-month intervals for 13 premenopausal Oriental women,
recent immigrant arrivals in Hawaii with presumed low risk of breast
cancer, and for 12 premenopausal Finnish women with presumed higher ri
sk. The urinary estrogen profile was measured by gas chromatography-ma
ss spectrometry and plasma and fecal estrogens were assayed by chromat
ographic radioimmunoassays. Results: Mean fat intake per 1000 kcal was
73% higher (P<.001) in the Finnish women, but the mean fiber intake a
nd fecal weights were similar to those of the Oriental women. Compared
with Oriental women, Finnish women had 46% higher plasma estradiol (P
<.01) and 124% higher plasma estrone sulfate (P<.01); however, after a
djustment for differences in age and body mass index, only the differe
nce in estrone sulfate remained statistically significant (P<.05). Mea
n plasma levels of estrone and estradiol correlated with height after
adjustment for body mass index (P<.05). Mean plasma levels of estrone
and sex hormone-binding globulin were similar. The Finns had higher me
an urinary estrone (193%), estradiol (166%), various catechol estrogen
s (130%-439%), and total estrogen excretion (123%) (all P<.001), but s
imilar 16 alpha-hydroxylated estrogen excretion. As calculated, 16 alp
ha-hydroxylation of estrone was significantly increased (P<.01) in Ori
ental women, but 2-hydroxylation, 4-hydroxylation, and 16 beta-hydroxy
lation of estrone were similar in both groups. The ratio of catechol e
strogen to 16 alpha-hydroxylated estrogen was four to five times highe
r (P<.001) in the Finnish women. The Oriental women had two to three t
imes higher fecal excretion of estrogens than the Finnish women (P<.01
). Conclusions: Our results indicate that high catechol estrogen forma
tion may be a greater risk factor for breast cancer than high 16 alpha
-hydroxylation of estrogens. However, the main risk factor for the Fin
nish women, as opposed to the Oriental women, may be their higher estr
ogen levels that result from a higher fat diet, higher estrogen produc
tion related to their greater height, and lower fecal estrogen excreti
on.