All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate.
As a result, 15 SNPs on or near 12 genes and one miRNA with strong evidence of association with lung cancer risk were identified, including TERT (rs2736098), CHRNA3 (rs1051730), AGPHD1 (rs8034191), CLPTM1L (rs401681 and rs402710), BAT3 (rs3117582), TRNAA (rs4324798), ERCC2 (Lys751Gln), miR-146a2 (rs2910164), CYP1B1 (Arg48Gly), GSTM1 (null/present), SOD2 (C47T), IL-10 (-592C/A and -819C/T), and TP53 (intron 6).
Immunohistochemistry was used to examine CLPTM1L expression levels on a tissue microarray containing 73 sets of human lung cancer specimens with adjacent normal tissue.
Our results verified that certain CLPTM1L polymorphisms are protective factors against lung cancer in a southern Chinese Han population and may be potential diagnostic and molecular markers for lung cancer patients.
We observed statistically significant associations with melanoma for two lung cancer SNPs in the TERT-CLPTM1L locus (Bonferroni-corrected p<2.8x10-4), replicating known pleiotropic effects at this locus.
The long TL genetic score was significantly associated with increased risk of lung adenocarcinoma (P = 6.3 × 10(-15)), even after exclusion of a SNP residing in a known lung cancer susceptibility region (TERT-CLPTM1L) P = 6.6 × 10(-6)).
The differences in risk level between Israeli Jews and non-Jews could not be explained by lung cancer genetic risk variants which were identified in GWAS (genes in the CHRNA5, TERT and CLPTM1L regions).
This study examined associations between five single nucleotide polymorphisms (SNPs) of TERT-CLPTM1L (rs402710, rs401681, rs465498, rs4975616, and rs2736100) and lung cancer in a Chinese Han population in the Hubei Province.
Taken together, our results establish a protumorigenic role for CLPTM1L that is critical for Ras-driven lung cancers, with potential implications for therapy and chemosensitization.
Taken together, our results establish a protumorigenic role for CLPTM1L that is critical for Ras-driven lung cancers, with potential implications for therapy and chemosensitization.
In conclusion, our study indicated that the CLPTM1L - rs401681 (G>A) polymorphism was significantly associated with decreased lung cancer risk, especially among European populations.
We evaluated 23 single nucleotide polymorphisms (SNPs) in the five nicotinic receptor related genes (CHRNB3, CHRNA6, and CHRNA5/A3/B4) previously reported to be associated with lung cancer risk and smoking behavior and 14 SNPs in the four 'control' genes (TERT, CLPTM1L, CYP1A1, and TP53), which were not reported in the smoking GWA studies.
This study aimed to investigate the association between polymorphisms in TERT and CLPTM1L genes with the risk of lung cancer, as well as the interaction of the polymorphisms and the environmental risk factors in Chinese non-smoking females.
However, the joint effect of TERT and CLPTM1L variants increased the risk of lung cancer, especially squamous cell carcinoma, with an adjusted OR of 3.274.