Association between FTO gene polymorphisms and breast cancer: the role of estrogen

ABSTRACT

Introduction: The fat mass and obesity-associated (FTO) gene may be associated with breast cancer risk. This study aimed to systematically investigate the association between FTO gene polymorphisms and breast cancer and the possible role of estrogen in this association.

Areas covered: We performed an extensive search of electronic databases such as PubMed, Science Direct, Scopus, and Cochran for published original studies on the association of FTO gene polymorphisms with breast cancer risk. Keywords such as breast cancer and/or FTO gene and/or polymorphism were used in order to identify the related articles. We excluded studies unrelated to the FTO genotype and the outcome of breast cancer.

Expert opinion: FTO gene may have a significant association with the risk of breast cancer. The association between FTO gene polymorphisms and breast cancer was influenced by the status of estrogen receptors. Estrogen may promote breast cancer cell proliferation through up-regulation of FTO gene expression and activation of the PI3 K/Akt signaling pathway in estrogen receptor positive patients. Further studies are warranted to identify the underlying mechanisms and signaling pathways involved in the interactions between FTO gene, estrogen, and the risk of breast cancer.

KEYWORDS:

• Breast cancer
• FTO gene
• genotype
• polymorphism

Article highlights

• FTO genotype may play an important role in breast cancer.

• The association between FTO gene polymorphisms and breast cancer was different between studies.

• The association between FTO genotype and breast cancer may be influenced by the stage of cancer, the status of estrogen/progesterone receptors, and BMI.

• It is possible that estrogen exerts its effects on BC through the FTO gene.

• FTO polymorphisms had a strong association with BC only in estrogen receptor-positive patients.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership, or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study is related to the project NO. 1397/3900 from Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran.