Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer
- Resource Type
- Authors
- Vida Stegel; Srdjan Novaković; Ksenija Gersak; Maja Pohar-Perme; Snjezana Frkovic-Grazio; Jasmina Ziva Cerne
- Source
- Oncology Reports.
- Subject
- Oncology
Cancer Research
medicine.medical_specialty
Genotype
Hormone Replacement Therapy
medicine.drug_class
Breast Neoplasms
Biology
Catechol O-Methyltransferase
GSTP1
Breast cancer
Risk Factors
Internal medicine
medicine
Humans
Aged
Aged, 80 and over
Polymorphism, Genetic
Superoxide Dismutase
Case-control study
Cancer
Estrogens
General Medicine
Odds ratio
Middle Aged
medicine.disease
Postmenopause
Endocrinology
Glutathione S-Transferase pi
Estrogen
Case-Control Studies
Cytochrome P-450 CYP1B1
Female
Aryl Hydrocarbon Hydroxylases
Breast disease
- Language
- ISSN
- 1791-2431
1021-335X
Association between long-term hormone replacement therapy (HRT) use and increased risk of breast cancer is still under debate. Functionally relevant genetic variants within the estrogen metabolic pathway may alter exposure to exogenous sex hormones and affect the risk of postmenopausal breast cancer. We investigated the associations of common polymorphisms in 4 genes encoding key proteins of the estrogen metabolic pathway, duration of HRT use and their interactions with breast cancer risk. We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women. Duration of HRT use was ascertained through a postal questionnaire. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695) and MnSOD (rs4880) polymorphisms by PCR-based RFLP and TaqMan® allelic discrimination method. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression analysis. HRT use was significantly associated with decreased breast cancer risk (p0.001). None of the polymorphisms studied was associated with breast cancer risk. A significant interaction was observed between MnSOD 47TC and HRT use (pinteraction=0.036); the risk of breast cancer associated with long-term vs. short-term HRT use was decreased in women homozygous for the wild-type allele and increased in women with at least one variant allele of the MnSOD 47TC polymorphism. Our results suggest that MnSOD 47TC polymorphism in interaction with long-term HRT use may modify the risk of breast cancer.