Association of CYP17 genetic polymorphism with intra-tumoral estradiol concentrations but not with CYP17 messenger RNA levels in breast cancer tissue

• Published in: Cancer letters 2003-05, Vol.195 (1), p.81-86
• Main Authors: Miyoshi, Yasuo, Ando, Akiko, Ooka, Masaru, Shiba, Eiichi, Taguchi, Tetsuya, Tamaki, Yasuhiro, Noguchi, Shinzaburo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alleles; Amino Acid Substitution; Binding sites; Biological and medical sciences; Biosynthesis; Breast cancer; Breast Neoplasms - enzymology; Breast Neoplasms - pathology; CYP17; Enzymes; Estradiol - analysis; Estrogens; Female; Genotype & phenotype; Humans; Medical sciences; Menopause; Messenger RNA; Middle Aged; Neoplasm Proteins - chemistry; Neoplasm Proteins - genetics; Neoplasms, Hormone-Dependent - enzymology; Patients; Polymerase Chain Reaction; Polymorphism; Polymorphism, Single Nucleotide; Receptors, Estrogen - analysis; RNA, Messenger - analysis; RNA, Neoplasm - analysis; Steroid 17-alpha-Hydroxylase - chemistry; Steroid 17-alpha-Hydroxylase - genetics
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(02)00211-2

The variant allele 1931C of CYP17 (1931C/T), which is one of the key enzymes involved in estrogens synthesis, has been shown to be associated with breast cancer risk. Since this variant allele creates an additional putative Sp-1 binding site (CCAC C ) in the promoter region, it is speculated that it enhances the transcription of CYP17, leading to the enhanced estrogens synthesis in breast tumors. CYP17 messenger RNA (mRNA) expression could be detected in all the normal breast ( n=51) and tumor tissues ( n=67) by a real-time polymerase chain reaction but CYP17 mRNA expression was not significantly different between the variant allele carriers and non-carriers. In addition, no significant correlation was observed between CYP17 mRNA and E2 levels in tumors, indicating an unimportant role of CYP17 in in situ synthesis of E2. On the other hand, intra-tumoral E2 levels were significantly ( P=0.025) higher in the variant allele carriers (127.2±11.0 pg/g) than non-carriers (88.2±8.5 pg/g). Since it has been previously reported that serum E2 levels are higher in variant allele carriers than non-carriers, it is speculated that the higher intra-tumoral E2 levels in the variant allele carriers might be ascribed to the higher serum E2 levels.