A functional variant in the flanking region of pri-let-7f contributes to colorectal cancer risk in a Chinese population.

Let-7f was reported to be downregulated in patients with colorectal cancer (CRC). However, little is known about the role of let-7f in CRC carcinogenesis. The aim of this study was to investigate the correlation between genetic polymorphisms in the flanking region of pri-let-7f and CRC risk, as well as the potential role of let-7f in CRC cell migration and invasion. The pri-let-7f-1 rs10739971 and pri-let-7f-2 rs17276588 were genotyped using TaqMan (Applied Biosystems, Foster City, CA) assay. The luciferase activity was detected using Dual-Luciferase Reporter Assay. CRC cell migration and invasion were evaluated using transwell chamber assay. The rs17276588 AG and AG/AA genotypes had a significantly increased CRC risk (AG vs. GG: adjusted odds ratio [OR] = 1.48, 95% confidence interval [CI] = 1.19-1.83, p < 0.001; AG/AA vs. GG: adjusted OR = 1.43, 95% CI = 1.17-1.75, p < 0.001). Stratification analyses showed that the increased risk was observed in CRC patients with well-moderately differential status, patients with clinical Stages I-II, and patients without lymph node metastasis. The rs17276588A allele displayed a decreased transcriptional activity and low levels of let-7f. Moreover, let-7f inhibited migration and invasion in Caco-2 and Lovo cells. These findings indicate that the rs17276588 AG/AA genotypes increased CRC risk by reducing the expression of tumor suppressor let-7f.