Determinants of p14/ARF methylation in healthy females: association with reproductive and non-reproductive risk factors of breast cancer

Abstract

BackgroundDNA methylation is associated with the risk factors of breast cancer. However, the impact of the reproductive and non-reproductive risk factors of breast cancer on p14/ARF methylation is not well known. Therefore, we investigated the relationships between p14/ARF methylation percentage and risk factors of breast cancer including age, family history, obesity, and reproductive risk factors in 120 breast cancer-free subjects; 60 women with a first-degree family history of breast cancer and 60 age-matched women with no family history of breast cancer. Extracted DNA from the whole blood was bisulfite-treated by EZ DNA modification kit. Quantitative methylation of p14/ARF was analyzed by methylation-specific PCR then methylation percentage of p14/ARF was calculated.ResultsP14/ARF methylation percentage was not related to any of the risk factors of breast cancer except age. Our study showed that p14/ARF methylation percentage was significantly higher in females with age ≥ 40 years than in females with age < 40 years (p=0.029). Also, a positive significant correlation between the p14/ARF methylation percentage and age was detected (r = 0.285, p = 0.014). Furthermore, univariate regression analysis showed that the age is independently associated with high p14/ARF methylation percentage (β = 1. 46, p = 0.029).ConclusionAmong healthy females, the age is strongly linked to the peripheral p14/ARF methylation percentage. The present study suggests that p14/ARF methylation is not associated with other breast cancer risk factors. These results need oncoming research on a large cohort to define the interactions between p14/ARF methylation and the risk factors of breast cancer.