Genetic variants of PTPN2 are associated with lung cancer risk: a re-analysis of eight GWASs in the TRICL-ILCCO consortium.

Sci Rep 2017 04 11;7(1):825. Epub 2017 Apr 11.

Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA.

The T-cell protein tyrosine phosphatase (TCPTP) pathway consists of signaling events mediated by TCPTP. Mutations and genetic variants of some genes in the TCPTP pathway are associated with lung cancer risk and survival. In the present study, we first investigated associations of 5,162 single nucleotide polymorphisms (SNPs) in 43 genes of this TCPTP pathway with lung cancer risk by using summary data of six published genome-wide association studies (GWAS) of 12,160 cases and 16,838 controls. We identified 11 independent SNPs in eight genes after correction for multiple comparisons by a false discovery rate <0.20. Then, we performed in silico functional analyses for these 11 SNPs by eQTL analysis, two of which, PTPN2 SNPs rs2847297 and rs2847282, were chosen as tagSNPs. We further included two additional GWAS datasets of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls), and the overall effects of these two SNPs among all eight GWAS studies remained significant (OR = 0.95, 95% CI = 0.92-0.98, and P = 0.004 for rs2847297; OR = 0.95, 95% CI = 0.92-0.99, and P = 0.009 for rs2847282). In conclusion, the PTPN2 rs2847297 and rs2847282 may be potential susceptible loci for lung cancer risk.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-00850-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429754PMC
April 2017
58 Reads
5.080 Impact Factor

Publication Analysis

Top Keywords

lung cancer
12
tcptp pathway
12
cancer risk
12
associated lung
8
snps genes
8
genetic variants
8
genes tcptp
8
pathway associated
4
controls identified
4
16838 controls
4
study investigated
4
survival study
4
risk survival
4
mutations genetic
4
association studies
4
independent snps
4
mediated tcptp
4
identified independent
4
investigated associations
4
tcptp mutations
4

Similar Publications