These results suggest that genetic variants in the TERT-CLPTM1L gene may predispose individuals to be susceptible to LC, particularly NSCLC, in the Chinese population.
Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China.
In the logistic regression analysis, TERT-rs2853669, rs2736108, and CLPTM1L-rs31490 were significant associated with increased risk of lung cancer (OR = 1.46, 95% CI = 1.22-1.75; OR = 1.22, 95% CI = 1.00-1.49 and OR = 1.74, 95% CI = 1.35-2.23 under additive model, respectively).
Recent genome-wide association studies and consecutive validation supported that the 5p15.33 region containing telomerase reverse transcriptase gene (TERT) and cleft lip and palate transmembrane protein 1-like (CLPTM1L) gene showed significant association with lung cancer in multiple populations.
Common genetic polymorphisms on chromosome 5p15.33, including rs401681 in cleft lip and palate transmembrane 1-like gene (CLPTM1L), have been implicated in susceptibility to lung cancer through genome-wide association studies (GWAS); however, subsequent replication studies yielded controversial results.
CLPTM1L transferred lung cancer cell line 95-D showed no growth inhibition or cell apoptosis, but it did show inhibited sensitivity to cis-diamminedichloroplatinum(II) (cisplatin, CDDP).
The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 × 10(-8)) located in TP63 (rs4488809 at 3q28, P = 7.2 × 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 × 10(-20) and P = 1.0 × 10(-27), respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 × 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 × 10(-11) and P = 6.2 × 10(-13), respectively).
In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.
Chromosome 5p15.33, containing TERT and CLPTM1L genes, was recently identified as one of the susceptible regions for lung cancer in Caucasian populations.
These data demonstrate a potential association between the TERT-CLPTM1L variant and levels of bulky DNA adducts measured by (32)P-postlabeling and hence a basis for susceptibility to the development of lung cancer.