Volume 2 Supplement 1

Second International Symposium on the Molecular Biology of Breast Cancer

Open Access

Genetic variants of CYP19 (aromatase) and breast cancer risk

  • V Nedelcheva Kristensen1,
  • N Harada3,
  • N Yoshimura3,
  • E Haraldsen1,
  • PE Lønning4,
  • B Erikstein2,
  • R Kåresen5,
  • T Kristensen6 and
  • A-L Børresen-Dale1
Breast Cancer Research20002(Suppl 1):P2.04

https://doi.org/10.1186/bcr153

Published: 12 March 2000

Full text

The effect of an SNP in exon 10 of CYP19 on tumour mRNA levels and splice variants was studied and correlated with clinical parameters and risk of breast cancer. In the vast majority of breast cancers, the estrogen levels modulate the tumour growth and depend on the activity of CYP19. Patients (n =481) and controls (n =236) were genotyped by T-tracks in a single sequencing reaction (SSR). The frequency of TT genotypes was significantly higher in patients versus controls (P =0.007) particularly among those with stage III and IV disease (P =0.004) and with tumours larger than 5 cm (P =0.001). A significant association between presence of the T allele and the level of aromatase mRNA in the tumours was observed (P =0.018), as well as with a switch from adipose promoter to ovary promoter (P =0.004). Previously, we reported a rare polymorphic allele of CYP19 (repeat (TTTA)12) to be significantly more frequent in breast cancer patients than in controls. Here we describe another polymorphism, a C-T substitution in exon 10 of the CYP19 gene which is in strong linkage disequilibrium with the (TTTA)n polymorphism but with higher frequency of the variant allele. Our data suggest that the T-allele of the CYP19 gene is associated with a `high activity' phenotype.

Authors’ Affiliations

(1)
Department of Genetics
(2)
Department of Oncology, Institute of Cancer Research, The Norwegian Radium Hospital
(3)
Department of Biochemistry, School of Medicine, Fujita Health University
(4)
Department of Oncology, Haukeland Hospital, University of Bergen
(5)
Department of Oncology, Ulleval Hospital
(6)
Department of Biochemistry, University of Oslo

Copyright

© Current Science Ltd 2000

Advertisement