Genetic Variants of CLPP and M1AP Are Associated With Risk of Non-Small Cell Lung Cancer.

Background: Single nucleotide polymorphisms (SNPs) are often associated with distinct phenotypes in cancer. The present study investigated associations of cancer risk and outcomes with SNPs discovered by whole exome sequencing of the normal lung tissue DNA of 15 non-small cell lung cancer (NSCLC) patients, 10 early stage and 5 advanced stage. Methods: DNA extracted from the normal lung tissue of the 15 NSCLC patients was subjected to whole genome amplification and sequencing and analyzed for the occurrence of SNPs. The association of SNPs with the risk of lung cancer and survival was surveyed using the OncoArray study dataset of 85,716 patients (29,266 cases and 56,450 cancer-free controls) and the Prostate, Lung, Colorectal and Ovarian study subset of 1,175 lung cancer patients. Results: We identified 4 SNPs exclusive to the 5 patients with advanced stage NSCLC: rs10420388 and rs10418574 in the CLPP gene, and rs11126435 and rs2021725 in the M1AP gene. The variant alleles G of SNP rs10420388 and A of SNP rs10418574 in the CLPP gene were associated with increased risk of squamous cell carcinoma (OR = 1.07 and 1.07; P = 0.013 and 0.016, respectively). The variant allele T of SNP rs11126435 in the M1AP gene was associated with decreased risk of adenocarcinoma (OR = 0.95; P = 0.027). There was no significant association of these SNPs with the overall survival of lung cancer patients (P > 0.05). Conclusions: SNPs identified in the CLPP and M1AP genes may be useful in risk prediction models for lung cancer. The previously established association of the CLPP gene with cancer progression lends relevance to our findings.