Identification of a Low-Frequency Missense Variant in E2F Transcription Factor 7 Associated with Colorectal Cancer Risk In A Chinese Population

Background: Transcription factors regulate gene expression and play important role in tumor genesis. Especially, the E2F transcription factor family controls the cell cycle and regulate many tumor suppressors. Missense variants in E2F family genes, which change the amino acid sequence, may alter the capacity for DNA binding or the protein structure, leading to a functional alteration. Material and Methods: We here searched for missense variants in E2F transcription family genes (E2F1~E2F8) and identified two (rs2075995 for E2F2 and rs3829295 for E2F7) with minor allele frequencies >0.01 in Chinese Han Beijing population from the 1000 genome project. We genotyped these two variants in 1,055 colorectal cancer (CRC) patients and 1,936 healthy controls using Taqman genotyping assays and assessed associations between SNPs and risk of CRC using logistic regression adjusted for gender and age. Results: We found rs3829295 at E2F7 to be significantly associated with risk of CRC. Compared with TT genotype carriers, CT and CT+CC genotype carriers had lower risks of CRC with ORs of 0.61 (95% CI: 0.44-0.85, P=0.003) and 0.61 (95% CI: 0.44-0.84, P=0.003), respectively. When stratified by gender and age, significant associations were observed in males (OR= 0.56, 95% CI: 0.38-0.83, P=0.004) for rs3829295, but not females (OR= 0.73, 95% CI: 0.43-1.22, P=0.232). Conclusion: Through a systematic assessment of variants in the E2F transcription factor family, we identified a lowfrequent missense variant in E2F7 significantly associated with CRC risk, indicating that E2F7 may play an important role in development of this tumor type.