Lehrer S, Harlap S, Rabin J, Schachter BS. Estrogen receptor
polymorphism, spontaneous abortion, and breast cancer risk. Int J Oncol
In 1988 we identified a polymorphism in the estrogen receptor (ER) gene.
The newly identified allele, called B', contains a silent mutation in codon
87, part of the receptor's B domain. Because of the association we previously
reported of the B' allele, spontaneous abortion, and estrogen receptor
positive breast cancer, we have now performed a preliminary case-control study
to estimate the risk of breast cancer in women with the B' allele. Among BB'
heterozygotes with ER-positive breast cancers (23 cases, 27 controls), the
risk of this type of cancer was strongly related to a history of spontaneous
abortion; the age-adjusted odds ratios were 4.1 (95% confidence limits,
0.95-18) after one spontaneous abortion and 9.7 (1 .6-61) after two or more
spontaneous abortions. No such association was seen for the risk of
ER-negative breast cancer in BB' heterozygotes (N=18). Moreover, among BB
homozygotes (137 cancer patients, 235 controls), spontaneous abortion was not
related to an increased risk of breast cancer, either ER-positive or
ER-negative. In BB' patients with ER-positive tumors, receptor concentrations
were significantly lower in those who had a history of spontaneous abortion
than in those without previous spontaneous abortions. These findings suggest
involvement of a functional mutation associated with the B polymorphism, which
is either elsewhere in the ER gene region or in a closely linked gene .