Association of adiponectin and fat mass and obesity genetic variants with breast cancer risk in Egyptian females

Manal A Safan; Waheed M Salem; Yostena Mekhail; Mirna M Abdelfattah

doi:10.1016/j.gene.2025.149808

Association of adiponectin and fat mass and obesity genetic variants with breast cancer risk in Egyptian females

Gene. 2025 Nov 5:971:149808. doi: 10.1016/j.gene.2025.149808. Epub 2025 Oct 2.

Authors

Manal A Safan¹, Waheed M Salem², Yostena Mekhail³, Mirna M Abdelfattah⁴

Affiliations

¹ Medical Biochemistry & Molecular Biology, Faculty of Medicine, Menoufia University, Egypt.
² Analytical Chemistry, Faculty of Applied Health Sciences, Menoufia University, Egypt.
³ Clinical Oncology & Nuclear Medicine, Faculty of Medicine, Menoufia University, Egypt.
⁴ Medical Laboratories Technology, Faculty of Applied Health Sciences, Menoufia University, Egypt. Electronic address: Mirna.Muhammad@hsc.menofia.edu.eg.

PMID: 41045977
DOI: 10.1016/j.gene.2025.149808

Abstract

Background: Breast cancer (BC) remains the most common cause of cancer-related mortality in women worldwide, driven by a combination of genetic predisposition and environmental influences. Obesity is a major modifiable risk factor, and recent studies have implicated genetic variants in the Adiponectin (ADIPOQ) and Fat Mass and Obesity-associated (FTO) genes in increasing the risk of both obesity and breast cancer across various populations.

Objective: This study investigates the association between ADIPOQ rs2241766 and FTO rs9939609 polymorphisms with BC risk and clinicopathological features in Egyptian women.

Methods: A case-control study was conducted on 192 female participants (96 BC patients and 96 age- and sex-matched healthy controls). Genotyping was performed using TaqMan real-time PCR assays. serum levels of ADIPOQ, FTO, carcinoembryonic antigen (CEA), and cancer antigen 15-3 (CA15-3) was carried out using enzyme-linked immunoassay techniques. Clinical data were also analyzed.

Results: The TG and GG genotypes, as well as the G allele of ADIPOQ rs2241766, were significantly associated with increased BC risk (OR = 2.300 and 4.836, respectively; p < 0.05). The G allele was associated with younger age and hormone receptor-positive subtypes. Similarly, the TA and AA genotypes and A allele of FTO rs9939609 were significantly associated with increased BC risk (OR = 4.423 and 7.656, respectively; p < 0.001). BMI was significantly higher among BC patients (p < 0.001), highlighting the potential interaction between genetic and metabolic risk factors.

Conclusion: The ADIPOQ rs2241766 and FTO rs9939609 polymorphisms are significantly associated with elevated BC risk in Egyptian women. These variants may serve as genetic markers for susceptibility, supporting their integration into personalized risk assessment and prevention strategies, especially in populations with high obesity prevalence.

Keywords: ADIPOQ rs2241766; Breast cancer; FTO rs9939609; Precision oncology; Risk assessment.

MeSH terms

Adiponectin* / blood
Adiponectin* / genetics
Adult
Alpha-Ketoglutarate-Dependent Dioxygenase FTO* / blood
Alpha-Ketoglutarate-Dependent Dioxygenase FTO* / genetics
Breast Neoplasms* / genetics
Case-Control Studies
Egypt
Female
Genetic Predisposition to Disease
Genotype
Humans
Middle Aged
Obesity* / genetics
Polymorphism, Single Nucleotide
Risk Factors

Substances

Adiponectin
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
ADIPOQ protein, human
FTO protein, human