OP0016 Two novel loci of low-density lipoprotein receptor-related protein 5 associated with non-small-cell lung cancer risk

Abstract

Background Low-density lipoprotein receptor-related protein 5 (LRP5) acts as a co-receptor with Frizzled protein family members for transducing Wnt/β-catenin signalling, alteration of which contributes to human carcinogenesis; thus, LRP5 polymorphisms could contribute to cancer susceptibility. This study investigated single nucleotide polymorphisms (SNPs) in LRP5 on risk of developing non-small-cell lung cancer (NSCLC). Methods A total of 500 NSCLC patients and 500 healthy controls were recruited for genotyping of 11 SNPs in LRP5 . The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses. Findings A total of 1000 samples were collected in this study, including 500 patients (350 male, 150 female; 331 with adenocarcinoma [ADC], 169 with squamous cell carcinomas [SCC]; 281 male patients who were smokers or former smokers, 21 female patients who were smokers or former smokers) and 500 controls (359 male, 240 female [gender information for one control subject was missed]; 268 male controls who were smokers or former smokers, 14 female controls who were smokers or former smokers). Eleven tagSNPs were detected. Frequency of LRP5 rs3736228 T allele (18.9% in male patients and 23.9% in male controls) differed significantly between male patients and male controls ( p = 0.03) and the T allele was associated with a lower risk of NSCLC (OR = 0.74, 95% CI 0.56–0.67), whereas the C/C homozygous genotype and LRP5 rs64843 T/T genotype were associated with risk of NSCLC and SCC, respectively (OR = 1.43 and 1.77, respectively). Haploview identified two blocks in which the frequency of the haplotypes of 11 tagSNPs were non-significantly different between controls and cases or between control subgroups and cases subgroups. Interpretation LRP5 rs3736228 and rs64843 SNPs were significantly associated with increased risk of NSCLC and SCC, respectively. Further study will investigate functional changes in LRP5 expression and activity in NSCLC in vitro.