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CYP1B1 Gene Polymorphisms Have Higher Risk for Endometrial Cancer, and Positive Correlations with Estrogen Receptor and Estrogen Receptor ß Expressions

Department of Urology, University of California San Francisco and Veterans Affairs Medical Center, San Francisco, California 94121 [M. S., Y. T., M. K., R. D.], and Department of Obstetrics and Gynecology, School of Medicine, Hokkaido University, Kitaku, Sapporo, Japan [N. S.]

The estradiol metabolites by CYP1B1 received particular attention because of their causative role in malignant transformation of endometrium. We hypothesize that polymorphisms of CYP1B1 gene can predict higher incidence of endometrial cancer. To test this hypothesis, the genetic distributions of six different CYP1B1 gene polymorphisms were investigated, by sequence-specific PCR and direct DNA sequencing, in 113 Japanese endometrial cancer patients and 202 healthy controls. We also investigated whether the expression of estrogen receptors (ER and ERß), progesterone receptor, and androgen receptor genes are influenced by the CYP1B1 genotypes in endometrial cancer. The results of our study demonstrated that the distributions of CYP1B1 genotypes at codons 119 and 432 were significantly different between endometrial cancer patients and healthy normal controls. The relative risks of 119T/T and 432G/G in endometrial cancer were calculated as 3.32 and 2.49 compared with wild-types. The 119T/T showed significant correlation for positivities of ER and ERß. The 432G/G also showed weak correlations for ER positivity. Other loci, intron 1, codon 48, and codon 449 were not different between endometrial cancer patients and healthy normal control.

This is the first report that demonstrates that the rare polymorphisms at codons 119 and 432 of CYP1B1 gene have higher risk for endometrial cancer, and positive correlations with ER and ERß expressions in endometrial cancer.

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