Dietary modulation of pregnancy estrogen levels and breast cancer risk among female rat offspring.
OBJECTIVE
Against the hypothesis that high estrogen levels in utero increase the risk of developing breast cancer in later life are data showing that pregnancy estrogen levels are significantly higher in Asian women who have low breast cancer risk than in Caucasian women. We investigated whether maternal dietary intake of genistein or n-3 polyunsaturated fatty acids (PUFAs), which are typical to Asian but not Caucasian diet, affect pregnancy estrogen levels and susceptibility to mammary tumorigenesis among offspring.


METHODS
For that purpose, pregnant female Sprague Dawley rats were fed isocaloric AIN-93-based diets containing either at 15 mg (low), 150 mg (medium), or 300 mg (high)/kg genistein/diet or low- or high-fat (16 versus 39% energy from fat) diet composed either of n-3 PUFA menhaden oil or n-6 PUFA corn oil. All diets were switched to regular AIN-93 diet when pups were born.


RESULTS
Maternal intake of n-3 PUFA diets significantly increased pregnancy 17 beta-estradiol (E2) levels (48% increase when compared with high n-6 PUFA diet; P < 0.0045). High genistein exposure also increased pregnancy estrogen levels, but the increase did not reach statistical significance (P < 0.14). The offspring of high-fat n-3 PUFA-consuming dams were significantly less likely to develop 7,12-dimethylbenz-[a]anthracene-induced mammary tumors (38% of these rats developed tumors during week 17 versus 64% of high n-6 PUFA offspring; P < 0.003). Maternal genistein intake did not affect offspring's tumor incidence. The mammary glands of high fat n-3 PUFA offspring contained more lobules (P < 0.07) and were thus more differentiated, whereas the glands of high genistein offspring contained more terminal end buds (P < 0.0015), which are the sites of malignant transformation.


CONCLUSIONS
Our findings indicate that the elevated estrogen levels in the n-3 PUFA mothers were linked to reduced rather than increased breast cancer risk among their offspring, suggesting that other effects of n-3 PUFA may counteract the effects of high fetal estrogenicity on the mammary gland. High maternal genistein intake did not reduce offspring's breast cancer risk, and therefore high maternal soy intake in Asian women may not be associated with daughters' low breast cancer risk.
Hilakivi-Clarke
Leena
L
Department of Oncology, Lombardi Cancer Center, Washington, DC 20007, USA. Clarkel@gunet.georgetown.edu
Cho
Elisabeth
E
Cabanes
Ana
A
DeAssis
Sonia
S
Olivo
Susan
S
Helferich
William
W
Lippman
Marc E
ME
Clarke
Robert
R
D000821:Animal Feed; D000818:Animals; D004041:Dietary Fats; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology; D015674:Mammary Neoplasms, Animal / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D018811:Maternal Exposure; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012306:Risk; D013997:Time Factors
D004041:Dietary Fats; D004967:Estrogens; D005231:Fatty Acids, Unsaturated; D004958:Estradiol; D019833:Genistein