ESTROGEN-RECEPTOR POLYMORPHISM, SPONTANEOUS-ABORTION, AND BREAST-CANCER RISK
- S LEHRER
- S HARLAP
- J RABIN
- BS SCHACHTER
Affiliations: MEM SLOAN KETTERING CANC CTR,DEPT RADIAT ONCOL,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT EPIDEMIOL & BIOSTAT,NEW YORK,NY 10021. LONG ISL JEWISH MED CTR,DEPT OBSTET & GYNECOL,NEW HYDE PK,NY 11042. CUNY MT SINAI SCH MED,DEPT CELL BIOL & ANAT,NEW YORK,NY 10029.
- Published online on: October 1, 1994 https://doi.org/10.3892/ijo.5.4.861
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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.