This single nucleotide polymorphism (SNP) modified associations of soy isoflavones and tea consumption but not fiber intake with endometrial cancer, with the inverse association of soy intake and tea consumption being more evident for those with the Asp/Asp genotype of the SHBG gene at rs6259" genes_norm="6462">Asp(327)Asn (rs6259), particularly premenopausal women (P(interaction) = 0.06 and 0.02, respectively, for soy isoflavones and tea intake).
DNA samples from 150 cases of endometrial cancer and healthy controls (n = 165) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypic frequency of 13 different polymorphic loci on the CYP1A1 (m1, m2, m3, m4), CYP1A2 1F, CYP1B1 codon432, COMT codon158, CYP17, SULT1A1 (Arg213His, 14A/G, 85C/T in the 3' flanking region), SULT1E1-64G/A promoter region, and SHBG genes.
On the other hand, alteration to a relative increase in SHBG wild-type mRNA expression in the metastatic lesions occurred in only 3 cases (1/10 cases of uterine endometrial cancers and 2/10 cases of uterine cervical cancers) analyzed.
These findings suggest that intracellular SHBG suppression might partly contribute to the abolition of the intracellular estrogen-dominant milieu, and may be involved as one of the mechanisms of the antitumoral effects of high-dose MPA on the development and growth of some well-differentiated endometrial cancer cells.
These results suggest that dedifferentiation of endometrial cancers might induce a reduction in their estrogen-dependent properties via intracellular SHBG.
A decrease of intracellular SHBG caused by high-dose danazol or progesterone might partly contribute to the abolition of the intracellular estrogen-dominant milieu, and be related to the inhibition of estrogen-dependent growth of some endometrial cancer cells.