By analyzing 1000 genomes data for East Asian, we identified only one SNP in nearby region, rs402710, in high linkage disequilibrium with rs401681, which was also associated with lung cancer.
By analyzing 1000 genomes data for East Asian, we identified only one SNP in nearby region, rs402710, in high linkage disequilibrium with rs401681, which was also associated with lung cancer.
The rs401681 polymorphism was significantly associated with a decreased risk of lung cancer, bladder cancer, and basal cell carcinoma in Asians and in hospital-based studies.
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).
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).
After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)).
In conclusion, our study indicated that the CLPTM1L - rs401681 (G>A) polymorphism was significantly associated with decreased lung cancer risk, especially among European populations.
Significant multiplicative interactions were observed between gender and polymorphisms of rs402710, the "T/T" genotype of which was associated with decreased lung cancer risk in male patients (p = 0.016, OR = 0.35, 95 % CI: 0.17-0.73).
After that, a number of studies reported that the rs2736100, rs401681, rs402710, and rs31489 polymorphisms at chromosome 5p15 have been implicated in LC risk.
The results from our replication study and the meta-analysis provided firm evidence that rs402710 T allele significantly contributed to decreased lung cancer risk, and the case-control study implied that the variant may yield stronger effect on NSCLC and never smokers.
The single-nucleotide polymorphisms (SNP) at 5p15 (rs2736100, adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.03-1.67, P = 0.025; rs402710, aOR 0.82, 95% CI 0.69-0.98, P = 0.025; rs401681, aOR 0.82, 95% CI 0.69-0.98, P = 0.026) and at 15q25 (rs2036534, aOR 0.75, 95% CI 0.61-0.93, P = 0.01; rs6495309, aOR 0.81, 95% CI 0.65-1.00, P = 0.052) were significantly associated with lung cancer risk.
For lung cancer, which was the most studied tumor type, the estimated joint population attributable risk for three polymorphisms (TERT rs2736100, intergenic rs4635969, and CLPTM1L rs402710) was 41%.
The single-nucleotide polymorphisms (SNP) at 5p15 (rs2736100, adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.03-1.67, P = 0.025; rs402710, aOR 0.82, 95% CI 0.69-0.98, P = 0.025; rs401681, aOR 0.82, 95% CI 0.69-0.98, P = 0.026) and at 15q25 (rs2036534, aOR 0.75, 95% CI 0.61-0.93, P = 0.01; rs6495309, aOR 0.81, 95% CI 0.65-1.00, P = 0.052) were significantly associated with lung cancer risk.
In conclusion, rs402710 (5p15.33), rs16969968 and rs8034191 (both 15q25.1) and rs4324798 (6p22.1) were found to be unrelated to survival times in this large cohort of lung cancer patients, regardless of whether the cause of death was from lung cancer or not.