Offspring of women exposed in utero to diethylstilbestrol (DES): a preliminary report of benign and malignant pathology in the third generation.
BACKGROUND
Animal studies suggest that prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) causes epigenetic changes that may be transmitted to the next generation. Specifically, these studies show an elevated incidence of reproductive tumors in the female offspring of prenatally-exposed mice.


METHODS
We assessed cancer and benign pathology diagnoses occurring in the offspring of women whose prenatal exposure to DES (or lack of exposure) was verified by medical record. Our data arose from 2 sources: the mothers' reports of cancers occurring in 8216 sons and daughters, and pathology-confirmed cancers and benign diagnoses self-reported by a subset of 793 daughters.


RESULTS
Although statistical power is limited, our data are consistent with no overall increase of cancer in the sons or daughters of women exposed in utero to DES. Based on pathology-confirmed diagnoses reported by the daughters, we saw no association between DES and risk of benign breast disease or reproductive tract conditions. Based on 3 cases, the incidence of ovarian cancer was higher than expected in the daughters of women exposed prenatally to DES.


CONCLUSIONS
Our data do not support an overall increase of cancer risk in the sons or daughters of women exposed prenatally to DES, but the number of ovarian cancer cases was greater than expected. While preliminary, this finding supports continued monitoring of these daughters.
Titus-Ernstoff
Linda
L
Department of Community and Family Medicine, Dartmouth Medical School, and the Norris Cotton Cancer Center, Lebanon, NH 03756, USA. linda.titus-ernstoff@dartmouth.edu
Troisi
Rebecca
R
Hatch
Elizabeth E
EE
Hyer
Marianne
M
Wise
Lauren A
LA
Palmer
Julie R
JR
Kaufman
Raymond
R
Adam
Ervin
E
Noller
Kenneth
K
Herbst
Arthur L
AL
Strohsnitter
William
W
Cole
Bernard F
BF
Hartge
Patricia
P
Hoover
Robert N
RN
D000293:Adolescent; D000328:Adult; D001943:Breast Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004054:Diethylstilbestrol / Q000009:adverse effects*; D004968:Estrogens, Non-Steroidal / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007938:Leukemia / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D009679:Nuclear Family; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016016:Proportional Hazards Models; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology; D014565:Urogenital Neoplasms / Q000139:chemically induced / Q000453:epidemiology
D004968:Estrogens, Non-Steroidal; D004054:Diethylstilbestrol