A single nucleotide polymorphism (SNP) in a microRNA (miRNA)-binding site of KRT81 and time to recurrence (TTR) in patients (p) with surgically resected non-small cell lung cancer (NSCLC).

Abstract

10587 Background: miRNAs play an important role in carcinogenesis through the regulation of different genes. miR-SNPs are a novel class of SNPs that can affect miRNA biogenesis and miRNA target sites and can alter miRNA expression and functions. We have evaluated 11 miR-SNPs in a series of 175 resected NSCLC p and correlated our findings with TTR. Methods: In 175 NSCLC p who underwent complete surgical resection between March 1996 and December 2009, we examined 11 miR-SNPs: 5 in miRNA genes (miR-194-2 rs11231898; miR-196a-2 rs11614913; miR-149 rs2292832; miR-423 rs6505162; miR-146a rs2910164); 3 in miRNA binding sites (KRT81 rs3660; FAM179B rs1053667; AFF1 rs17703261) and 3 in miRNA-processing machinery (XPO5 rs11077; RAN rs14035; TRBP rs784567). DNA was obtained from paraffin-embedded or fresh frozen tumor tissue and allelic discrimination assay with ABI Prism 7500 was performed. Results: p characteristics: mean age, 65 (35-85); 88% male; 149 (85.1%) PS 1; 98 (56%) stage I, 40 (22.9%) stage II, 37 (21.1%) stage III; 80 (45.7%) adenocarcinoma, 84 (48%) squamous cell carcinoma, 11 (6.3%) other histologies; 28 (16%) received adjuvant treatment, 9 (5.1%) received neoadjuvant treatment; mean follow-up 35 months (m); 75 (42.9%) p relapsed. Only stage (P=0.008) and KRT81 genotype were associated with TTR. Median TTR for 45 p (25.9%) with the CC genotype was 20.3 m vs 86.8 m for p with the CG or GG genotype (P=0.003). Among 98 p with stage I disease, median TTR was 23.9 m for 25 p (25.5%) with the CC genotype vs 100.2 m for p with the CG or GG genotype (P=0.002). In the multivariate analysis, KRT81 CC genotype (OR, 2.14; 95%CI, 1.29-3.55; P=0.003), stage I disease (OR, 0.36; 95%CI, 0.18-0.73; P=0.005) and male sex (OR, 5.25; 95%CI, 1.56-17.73; P=0.008) emerged as independent variables for TTR. Conclusions: KRT81 rs3660 SNP may be a novel marker for TTR in resected NSCLC, mainly in stage I, where it can help to detect high-risk patients who may be candidates for adjuvant treatment.