Decreased risk of developing lung cancer in subjects carrying the CLPTM1L rs401681 (G&gt;A) polymorphism: evidence from a meta-analysis

Zhang, X.L.; Zhang, X.J.; Zhang, Y.M.; Zhang, Q.; Cao, Chunxiang; Gu, Dayong; Gong, Yongling; Chen, J.F.; Tang, Cuiju

doi:10.4238/2014.february.28.10

Cited by 5 publications

(2 citation statements)

References 37 publications

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“…Also associating with lung cancer risk was rs401681, a C/T intronic variant in CLPTM1L gene on chromosome 5p15.33; the T allele of rs401681 was previously found to associate with a lower risk of lung cancer in two meta-analyses 42 43 , and our results confirm these findings. On chromosome 8, we confirmed our previously observed association of the minor allele (G) of rs3019885 with increasing lung cancer risk 15 .…”

Section: Discussionsupporting

confidence: 89%

Genetic susceptibility variants for lung cancer: replication study and assessment as expression quantitative trait loci

Pintarelli¹,

Cotroneo

Noci³

et al. 2017

Sci Rep

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Many single nucleotide polymorphisms (SNPs) have been associated with lung cancer but lack confirmation and functional characterization. We retested the association of 56 candidate SNPs with lung adenocarcinoma risk and overall survival in a cohort of 823 Italian patients and 779 healthy controls, and assessed their function as expression quantitative trait loci (eQTLs). In the replication study, eight SNPs (rs401681, rs3019885, rs732765, rs2568494, rs16969968, rs6495309, rs11634351, and rs4105144) associated with lung adenocarcinoma risk and three (rs9557635, rs4105144, and rs735482) associated with survival. Five of these SNPs acted as cis-eQTLs, being associated with the transcription of IREB2 (rs2568494, rs16969968, rs11634351, rs6495309), PSMA4 (rs6495309) and ERCC1 (rs735482), out of 10,821 genes analyzed in lung. For these three genes, we obtained experimental evidence of differential allelic expression in lung tissue, pointing to the existence of in-cis genomic variants that regulate their transcription. These results suggest that these SNPs exert their effects on cancer risk/outcome through the modulation of mRNA levels of their target genes.The study of genetic factors modulating an individual's predisposition to lung cancer is supported by strong epidemiological evidence obtained from various types of studies. Observational studies have consistently reported an increased risk of lung cancer in first-degree relatives of lung cancer patients 1-5 . Genome-wide association studies (GWAS) on population-based series identified three main susceptibility loci, at 5p15 6-8 , 6p21 6 , and 15q25. The locus at 15q25 harbors genes for three nicotinic acetylcholine receptor subunits (CHRNA3, CHRNA5, and CHRNB4) that have previously been associated with lung cancer risk and nicotine dependence 6,9,10 . Other GWAS found many single nucleotide polymorphisms (SNPs) that associated with lung cancer risk [11][12][13][14][15][16] . However, the results obtained in these studies have not generally been confirmed, even in a large consortium study 17 .Some genetic variants associated with lung cancer risk have also been associated with prognosis. For instance, a polymorphism (rs6495309) in the promoter of CHRNA3 gene has been reported to be associated with the overall survival of patients with early-stage non-small-cell lung cancer (NSCLC) 18 . Moreover, rs667282 in CHRNA5 has recently been proposed as a modifier of prognosis in advanced NSCLC 19 . Several other SNPs, found using a GWAS approach, were proposed to be associated with prognosis or survival of lung cancer patients in different populations [20][21][22][23] . However, these studies did not identify the same candidate polymorphisms, which may be due (at least in part) to the wide genetic heterogeneity of the human population.The GWAS cited here, which aimed to find SNPs associated with lung cancer risk or prognosis, identified mostly non-overlapping subsets of SNPs, hindering progress in lung cancer research. One limitation of these studies is that they investigate...

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Section: Discussionsupporting

confidence: 89%

Genetic susceptibility variants for lung cancer: replication study and assessment as expression quantitative trait loci

Pintarelli¹,

Cotroneo

Noci³

et al. 2017

Sci Rep

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“…And meta-analysis is su cient to address these issues [47] . The results of previous meta-analysis con rmed the risk association between rs2736098, rs2736100, rs401681, rs402710, and rs31489 and LC, and analyzed the differences in LC susceptibility in different ethnic groups [48] [49][50] [51][52] [53][54] [55][56] [57][58] [59][60] [61] . However, most of these studies focused on single or several loci in the TERT-CLPTM1L region, and larger scale meta-analysis was still lacking.Tian J et al [62] recently conducted a large-scale meta-analysis and con rmed that eight sites in the TERT-CLPTM1L region (rs2853677, rs2242652, rs2736098, rs2736100, rs31489, rs401681, rs402710 and rs465498) were associated with LC risk, but they did not nd any other locus effects [2] .…”

Section: Introductionmentioning

confidence: 99%

Six minor allele variants in the TERT-CLPTM1L region are associated with lung cancer risk: a meta-analysis based on different ethnicities and different lung cancer subtypes

Luo

et al. 2023

Preprint

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Background: Although many genome-wide association studies(GWAS) have confirmed the associations between multiple sites in the TERT-CLPTM1L region and lung cancer(LC) susceptibility in different populations, some of them haven’t found the associations between these sites and LC. The purpose of this study is to clarify the associations between TERT-CLPTM1L polymorphism and LC, as well as the differences in these associations between patients of different ethnicities and different LC subtypes. Methods: Relevant literatures published before May 7, 2022 on ‘TERT-CLPTM1L polymorphisms and LC susceptibility’ in PubMed, EMbase,Web of Science, MEDLINE databases were searched through the Internet. Statistical analysis of data was performed in Revman5.3 software, including drawing forest plots, funnel plots and so on. Sensitivity and publication bias analysis were performed in Stata 14.0 software. TSA 0.9.5.10 software was performed for the Trial sequential analysis(TSA) tests to evaluate the stability of the results. Registration number: CRD42023407890. Results: A total of 51 literatures were included in this meta-analysis, including 6 TERT-CLPTM1L polymorphisms and a total of 54 studies (12 GWAS and 42 case-control studies), including 11 studies in Caucasians and 43 studies in Asians. The results showed that the minor allele variants of the 6 polymorphisms were positively or negatively associated with the risk of LC (rs2736098[T]: [OR]=1.24, 95% CI [1.18, 1.31]; rs2736100[C]: [OR]=1.25, 95% CI [1.20, 1.30]; rs31489[A]: [OR]=0.87, 95% CI [0.82, 0.92]; rs401681[T]: [OR]=0.87, 95% CI [0.84, 0.90]; rs402710[T]: [OR]=0.86, 95% CI [0.83, 0.88]; rs4975616[G]: [OR]=0.86, 95% CI [0.82, 0.91]). However, there were clear differences in these associations in LC with different pathological subtypes in Caucasian and Asian populations (Subgroup differences: I2≥50%). Conclusions: Our results confirmed the clear associations between 6 TERT-CLPTM1L polymorphisms and the risk of LC, and there were significant differences in these associations among different ethnicities/pathological subtypes of LC.

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Association of TERT-CLPTM1L and 8q24 Common Genetic Variants with Gallbladder Cancer Susceptibility and Prognosis in North Indian Population

et al. 2018

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Gallbladder carcinoma (GBC) is one of the common malignancy of the biliary tract. Several genome wide and candidate gene studies have reported associations between multiple cancer types and single-nucleotide polymorphisms on 5p15.33 and 8q24.21 loci. However, predisposition potential of these genetic variants has not been assessed in GBC. We performed the present study to assess the potential of five polymorphisms on 5p15.33 and one on 8q24.21 locus in GBC risk and treatment response in patients undergoing chemoradiotherapy. We extracted genomic DNA from peripheral blood and genotyped selected SNPs using TaqMan allelic discrimination assays in 523 GBC cases and 274 controls from the north-Indian population. Statistical tests were performed to assess the association of selected common genetic variants with gallbladder cancer susceptibility and prognosis. Binary logistic regression analysis showed significant association of TERT rs2736100C > A [OR(CI) = 0.690(0.515-0.924), p value = 0.013], CLPTM1L rs401681C > T [OR(CI) = 0.586(0.405-0.847), p value = 0.004], and CASC8 rs6983267G > T [OR(CI) = 1.629(1.215-2.186), p value = 0.001] with GBC risk. Further, using multivariate logistic regression, we observed that haplotype CLPTM1L CC TERT TA MIR4457 G [OR(CI) = 7.52 (1.79-31.52), p value = 0.0064] is significantly associated with poor treatment response. In survival analysis, Kaplan-Meier survival curves showed significantly poor survival and COX regression suggested significantly higher hazard ratio in TT genotype carriers of CASC8 rs6983267 [OR(CI) = 4.28(1. 07-17.10), p value = 0.040] as compared to major allele and heterozygous (GG+GT) genotypes in metastatic GBC cases. The study revealed that 5p15.33 and 8q24.21 genetic variants significantly influence GBC risk and treatment response in north-Indian population.

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Decreased risk of developing lung cancer in subjects carrying the CLPTM1L rs401681 (G>A) polymorphism: evidence from a meta-analysis

Cited by 5 publications

References 37 publications

Genetic susceptibility variants for lung cancer: replication study and assessment as expression quantitative trait loci

Genetic susceptibility variants for lung cancer: replication study and assessment as expression quantitative trait loci

Six minor allele variants in the TERT-CLPTM1L region are associated with lung cancer risk: a meta-analysis based on different ethnicities and different lung cancer subtypes

Association of TERT-CLPTM1L and 8q24 Common Genetic Variants with Gallbladder Cancer Susceptibility and Prognosis in North Indian Population

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