Abstract 81P
Background
Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and no amplification of the human epidermal growth factors 2 (HER2) receptor. ATP-binding cassette superfamily G member 2 (ABCG2) is a transport protein that functions to eliminate xenobiotics in ATP dependent manner. The genetic variations might alter the gene expression, substrate specificity, and xenobiotics elimination function which ultimately affect the susceptibility of individuals towards cancer. The aim of this study is to investigate the association of ABCG2 34 G>A and 421 C>A polymorphisms in modulating TNBC susceptibility.
Methods
Genomic DNA was extracted from blood samples of 75 TNBC patients and 100 normal controls. The genotyping was performed by using the PCR-RFLP method and the genotype pattern was grouped into three, which are homozygous wildtype, heterozygous and homozygous variant. The genotype, allele, and haplotype frequencies with TNBC and pathological variables were calculated by using the independent χ2 test whereas the level of association was evaluated by deriving odds ratio (OR) with 95% confidence intervals (CI) using binary logistic regression analysis.
Results
The ABCG2 421 AA genotype was found to be significantly higher in stage III and metaplastic/medullary histology subtype as compared to stage I &II and infiltrating ductal carcinoma (p=0.015 and 0.028) respectively. The logistic regression analysis showed that ABCG2 421 AA genotype was significantly increasing the risk of developing higher tumor staging with OR of 9.042 (95% CI: 1.640-49.837, p=0.011) as compared to the wildtype genotype (CC). The allele analysis showed that the variant A allele significantly increase the risk of stage III by 3.011 times (95% CI: 1.417-6.398, p=0.003). The haplotype analysis suggested that ABCG2 34G/421A was associated with tumor stage III with OR: 2.347 (95% CI: 1.010-5.560, p=0.048).
Conclusions
In conclusion, ABCG2 34 G>A and 421 C>A polymorphisms increase the risk of developing higher tumor staging and could be a potential predictive biomarker for TNBC susceptibility risk and prognosis.
Legal entity responsible for the study
Ahmad Aizat Abdul Aziz.
Funding
This study was supported by Universiti Sains Malaysia Short Term Grant (304/PPSP/6315508).
Disclosure
All authors have declared no conflicts of interest.