Early Parity Epigenetic Footprint of FOXA1 Gene Body in Normal Breast Tissue of Iranian Women

Authors
Zahra Zendehbad 1
Pantea Izadi 1
Abdolreza Daraei 2
Mir Saeed Yekaninejad 3
Nahid Nafissi 4
Nasim Younosi 5
Ghasemali Khorasani 6
Javad Tavakkoly Bazzaz 1
1 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2 Genetic Department, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
3 Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
4 Surgical Department, School of Medicine, Iran University of Medical Science, Tehran, Iran
5 Surgical Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
6 Division of Plastic and Reconstructive Surgery, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
10.29252/ibj.23.2.99
Abstract
Background: Young age at first full-term pregnancy (FFTP) is an important factor in breast cancer risk reduction. It is postulated that this protective effect is the result of stable molecular signatures imprinted by physiological process of pregnancy, but the molecular mechanism of this protective role is unclear. The aim of the current study was to identify the effect of early FFTP on methylation status of FOXA1 gene body. FOXA1 is an essential transcription factor for mammary gland development and estrogen responsiveness of breast tissue. Methods: Fresh frozen normal breast tissues (n = 51) were collected from Iranian women who underwent cosmetic mammoplasty (27 nulliparous women and 24 parous women who have experienced first pregnancy before the age of 25). DNA was extracted and then methylated DNA immunoprecipitation (MeDIP) real-time PCR was used to assess FOXA1 gene body methylation. Results: Our results revealed that FOXA1 methylation level is significantly higher in early parous compared with nulliparous group (p = 0.041). Conclusion: Our study provides new hint about the association between early FFTP and epigenetic modifications within gene body of FOXA1 in normal breast tissue. More investigation is required for clarifying molecular mechanisms underlying this association in order to develop breast cancer prevention strategies.
Keywords
Breast cancer
DNA methylation
Epigenetics
FOXA1
Pregnancy