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. [ABSTRACT FROM AUTHOR]