Two novel susceptibility loci for non-small cell lung cancer map to low-density lipoprotein receptor-related protein 5.

This study investigated the effect of single-nucleotide polymorphisms (SNPs) of low-density lipoprotein receptor-related protein 5 (LRP5) on the risk of developing non-small cell lung cancer (NSCLC). A total of 500 NSCLC patients and 500 healthy controls were recruited for genotyping of 11 SNPs of 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. Eleven Tag SNPs were detected. The frequency of the LRP5 rs3736228 T allele (18.9% in male NSCLC cases and 23.9% in male controls) was statistically different between male NSCLCs 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 the LRP5 rs64843 T/T genotype were associated with an increased risk of NSCLC and squamous cell carcinoma (SCC), respectively (OR=1.43 and 1.77, respectively). Using Haploview software, the frequency of the haplotypes of rs312009/rs3120015/rs3120014 CCC was was significantly higher in female SCC cases compared with female controls (0.064 vs. 0.009, P=0.04). LRP5 rs3736228 and rs64843 SNPs were significantly associated with an increased risk of NSCLC and SCC, respectively. Further studies are required to investigate the functional changes in LRP5 expression and activity in NSCLC in vitro.