Genetic and epigenetic modifications of adiponectin gene: Potential association with breast cancer risk

Abstract

Background: Adipokines produced by adipose tissue are directly linked to obesity and may contribute to the pathogenesis of cancer. We hypothesized that genetic and epigenetic modifications in the adiponectin (ADIPOQ) gene and their impact on serum ADIPOQ levels may participate in increasing breast cancer (BC) risk. The present study aimed to investigate ADIPOQ +45 T/G gene polymorphism, methylation status at CpG sites −74 nucleotides (nt) and −283 nt of the ADIPOQ gene, and ADIPOQ serum levels in BC obese women.Methods: Serum ADIPOQ was measured by an enzyme-linked immunosorbent assay. ADIPOQ +45 T/G gene polymorphism and ADIPOQ promoter methylation status were determined using a polymerase chain reaction (PCR) and a methylationspecific PCR, respectively, in 120 obese women with BC and 120 age-matched controls.Results: ADIPOQ +45 GG genotype carriers had a significant increased risk of developing BC (odds ratio = 6.2, 95% confidence interval = 1.3-29.6, p = 0.02).ADIPOQ gene methylation at site −74 nt resulted in a 1.7-fold increased BC risk.Methylation at site -283 nt resulted in a 1.9-fold increased BC risk. Moreover serum levels of ADIPOQ were significantly decreased in BC patients and down-regulated in the presence of methylation in both examined sites. By contrast, no association between ADIPOQ gene polymorphism and serum ADIPOQ level was detected. Using both methylated sites in one panel detected cancer breast with 76.67% sensitivity and 62.18% accuracy.Conclusions: ADIPOQ +45 T/G polymorphism and ADIPOQ promoter methylation were found to be associated with BC risk in obese Egyptian women.

Diagnostic and prognostic value of FOXD1 expression in head and neck squamous cell carcinoma

“…Cancer results from accumulation of genetic and epigenetic modifications of oncogenes and tumor-suppressor genes, resulting in metabolic dysfunction and uncontrolled proliferation 41 , 42 . Amplification of DNA is the major genetic change that results in cancer-specific expression of critical genes 43 , 44 .…”

Interactions Between Adiponectin-Pathway Polymorphisms and Obesity on Postmenopausal Breast Cancer Risk Among African American Women: The WHI SHARe Study

“…The evidence on the association of SNPs in ADIPOQ and ADIPOR1 with breast cancer risk has been inconsistent (21)(22)(23)(24)(25). A previous study found that ADIPOQ rs17366568 influenced adiponectin plasma levels in non-Hispanic White women but not in AA women (55).…”

“…Only a few studies have identified genetic variants (i.e., single nucleotide polymorphisms [SNPs]) that were associated with functional and structural regulation of adiponectin and their association with breast cancer risk; but the findings were inconsistent and conducted mostly in population with European or Asian ancestry (21)(22)(23)(24)(25). In particular, rs1501299 in the adiponectin gene (ADIPOQ) was associated with an increased risk of breast cancer in some studies (21,23), but not in others (22).…”

“…In particular, rs1501299 in the adiponectin gene (ADIPOQ) was associated with an increased risk of breast cancer in some studies (21,23), but not in others (22). No consensus could be reached for ADIPOQ rs2241766, where a positive, a negative, and no associations with breast cancer risk have been reported across different studies (21)(22)(23)(24). Of these studies, one study was conducted in AA women reporting that only ADIPOQ rs1501299 was associated with increased breast cancer incidence (23).…”

Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer

“…Mahmoud et al confirmed that there was an association between adiponectin gene polymorphism, serum adiponectin level, and the risk of BC in obese and overweight postmenopausal women (42). Besides, Pasha et al simultaneously studied the genetic and epigenetic changes of the serum level of adiponectin gene and uncovered that polymorphism and promoter methylation of the adiponectin gene were associated with BC risk in obesity (43). A new noninvasive biomarker designed by evaluating the methylation status of the adiponectin gene promoter can be produced and used as an encouraging tool for early detection of BC.…”