Projects / Programmes
Genetics of breast cancer and hormone replacement therapy
| Code |
Science |
Field |
Subfield |
| 3.05.00 |
Medical sciences |
Human reproduction |
|
| Code |
Science |
Field |
| B790 |
Biomedical sciences |
Clinical genetics |
hormone replacement therapy, estrogen metabolism, polymorphisms, breast cancer
Researchers (20)
Organisations (4)
Abstract
Genetics of breast cancer and hormone replacement therapy
Breast cancer is the most common cancer in women in Slovenia; in the period 2000-2004, its crude incidence rate was 101/100,000. Hormone replacement therapy (HRT) is one of the known risk factors for breast cancer. The mechanism of carcinogenic estrogen action is related to the production of excessive concentrations of some metabolites in the process of inactivation of sex hormones.
Epidemiological data on HRT use among Slovenian patients diagnosed with breast cancer in a certain observation period will be collected. In these patients, certain SNP and microsatellite polymorphisms in the genes, CYP19, CYP1A2, CYP1B1, COMT, AKR1C4, involved in the estrogen and progesterone inactivation, will be determined. The analysis will involve the expression profiles of the selected genes in tumour and healthy tissue samples. The expected results have an important practical value in health care and in improvement of quality of life. Prior to HRT prescription, the women could be offered a genetic counselling, genotype determination, and appropriate adjustment of their postmenopausal management to their individual needs.
Significance for science
The project was successfully realized and contributed to the pool of knowledge in the fields of medicine (human reproduction, oncology) and natural sciences (pharmacology, molecular biology). Interdisciplinary approach to the most frequent cancer in woman provided the basis for identification of: some new breast cancer risk factors risk factors for its development and contributed to the field of personal genomics.
Our results showed that hormone replacement therapy (HRT) use was inversely associated with breast cancer risk. The effect was most pronounced with estrogen use only but longer duration of HRT use did not result in evident improvement. Our analysis revealed some differences from the previously published literature, which might reflect underlying demographic changes. A comprehensive medical care in HRT users without preexisting breast abnormalities probably reduces the incidence of new breast cancer cases in Slovenia.
When the effects of some genotypes in estrogen metabolic genes were investigated, our results suggest that individual susceptibility to breast cancer incidence may be increased by combined effects of the high-risk genotypes in CYP1B1, COMT and MnSOD genes.
A significant interaction was observed between MnSOD 47T>C and HRT use; the wild-type allele in interaction with long-term HRT use may modify the risk of breast cancer.
The project results are presented in 11 completed works:
- 3 published original scientific articles (COBISS.SI-ID 28234457, 1089147, 1027195)
- 3 original scientific articles in press
- 2 published conference contribution (invited lecture) (COBISS.SI-ID 26212569, 25009369)
- 2 published scientific conference contribution (COBISS.SI-ID 27112409, 27434969)
- 1 Doctoral Dissertation (PhD defense in May 2011)
Significance for the country
As far as we know this was the first study to examine the influence of hormone replacement therapy (HRT) use and of some generally recognized risk factors on breast cancer risk among Slovenian postmenopausal women.
This was also the first evaluation of the associations between HRT use and breast tumor characteristics in Slovenian postmenopausal women diagnosed with invasive breast cancer.
Our results suggest that individual susceptibility to breast cancer incidence among Slovenian postmenopausal women may be increased by combined effects of the high-risk genotypes in CYP1B1, COMT and MnSOD estrogen metabolic genes.
Results have an important practical impact on the detection of risk factors in breast cancer in our population and can improve public health care. To offer genetic counselling and identification of the genotype and we can contribute to the individual management of the postmenopausal period for each women prior to the prescription of HRT.
The results were presented as two invited lectures at the annual symposia of Slovenian menopausal association 2008 and at 4th Congress of Slovene Association of Gynaecologists and Obstetricians 2009.
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
