novel variant identified in the enhancer region of host transcription factor, brn3a, is a significant risk factor for hpv-induced uterine cervix cancer

Among hpv-mediated cervical cancers, cellular factor brn3a has gained considerable attention due to its role in promoting an anti-apoptotic cellular environment and in facilitating epitheliotropic transformations of the host. the majority of previous studies looked at brn3a’s molecular characteristics; however, the possibility of genetic variations in brn3a’s auto-regulatory region in relation to cervical cancer risk has been underestimated until now. in a retrospective study in the eastern up population, india, we detected genetic variations in the cis-regulatory proximal enhancer region located around 5.6 kb upstream of transcription start site of brn3a. our analysis of pcr and dna sequencing confirmed this novel snp (brn3a g.60163379a>g) within the auto-regulatory region of brn3a. as compared to control subjects, cancer cases exhibited a 1.32-fold higher allele frequency (χ2 = 6.315, p = 0.012). in homozygous (gg) but not in heterozygous conditions, odds ratio (or) analysis suggests a significant association of cancer risk with the snp (or = 2.60, p ≤ 0.004). we further confirmed using the functional analysis that this snp increased the luciferase gene activity in hpv-positive cervical cancer siha cells that were exposed to progesterone. as a result of the association of polymorphisms in a non-coding region of an oncogene with increased cancer risks, we are suggesting that this genetic variation in non-coding region can be used in prediction, diagnosis, or predicting the progression of the disease.