DNA methylation of the long intergenic noncoding RNA 299 gene in triple-negative breast cancer: results from a prospective study.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with a high rate of recurrence and poor prognosis. Recently we identified a hypermethylation in the long noncoding RNA 299 (LINC00299) gene in blood-derived DNA from TNBC patients compared with healthy controls implying that LINC00299 hypermethylation may serve as a circulating biomarker for TNBC. In the present study, we investigated whether LINC00299 methylation is associated with TNBC in a prospective nested breast cancer case-control study within the Generations Study. Methylation at cg06588802 in LINC00299 was measured in 154 TNBC cases and 159 breast cancer-free matched controls using MethyLight droplet digital PCR. To assess the association between methylation level and TNBC risk, logistic regression was used to calculate odd ratios and 95% confidence intervals, adjusted for smoking status. We found no evidence for association between methylation levels and TNBC overall (P = 0.062). Subgroup analysis according to age at diagnosis and age at blood draw revealed increased methylation levels in TNBC cases compared with controls in the young age groups [age 26-52 (P = 0.0025) and age 22-46 (P = 0.001), respectively]. Our results suggest a potential association of LINC00299 hypermethylation with TNBC in young women.