Leukocyte telomere length‐related genetic variants in 1p34.2 and 14q21 loci contribute to the risk of esophageal squamous cell carcinoma

Shi, Juan; Sun, Fang; P, Li; Li, Bo; Liu, Li; Zhou, Changchun; Han, Jianjun; Zhang, Li; Zhou, Lixin; Zhang, Xiaojiao; Pu, Honglei; Tong, Lei; Yuan, Qipeng; Song, Xianrang; Yang, Ming

doi:10.1002/ijc.27959

Cited by 25 publications

(19 citation statements)

References 40 publications

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“…In addition, we found that both rs621559 and rs398652 genetic variants have obvious impact on LTL and ESCC susceptibility in Chinese [26]. In line with these findings, our current study also confirmed that only rs621559 and rs398652 influence risk of HBV-related HCC among all eleven GWAS-identified LTL-related SNPs.…”

Section: Discussionsupporting

confidence: 88%

“…Therefore, we believe that the positive association between rs398652 or rs621559 SNPs and HBV-related HCC was not due to predisposition to HBV infection. Interestingly, these two SNPs were associated with LTL in healthy Chinese subjects in our previous study [26]. The rs621559 A allele was a protective allele; subjects with the AG or AA genotype had an OR of 0.72 (95% CI = 0.61–0.85, P = 1.2×10 −4 ) or 0.74 (95% CI = 0.63–0.87, P = 2.2×10 −4 ) for developing HBV-related HCC, respectively, compared with subjects with the GG genotype (Trend test, P = 1.2×10 −6 ) (Table 3).…”

Section: Resultsmentioning

confidence: 72%

“…In a large case–control study, they observed that subjects with the variant allele of rs398652 has a significantly reduced risk of bladder cancer [Odds ratio (OR) = 0.81; 95% Confidence interval (CI) = 0.67–0.97; P = 0.025], consistent with the correlation of this variant allele with longer telomeres. In a previous study, we also investigated whether these four genetic variants are associated with LTL and risk of esophageal squamous cell carcinoma (ESCC) in Chinese populations [26]. After measuring LTL of 550 healthy individuals, we verified that both rs621559 and rs398652 genetic variants are significantly associated with LTL.…”

Section: Introductionmentioning

confidence: 85%

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Leukocyte Telomere Length-Related rs621559 and rs398652 Genetic Variants Influence Risk of HBV-Related Hepatocellular Carcinoma

et al. 2014

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Recent genome-wide association studies (GWAS) have identified eleven leukocyte telomere length (LTL)-related single nucleotide polymorphisms (SNPs). Since LTL has been associated with risk of many malignancies, LTL-related SNPs may contribute to cancer susceptibility. To test this hypothesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we genotyped these eleven LTL-related SNPs in a case-control set including 1186 HBV-related HCC cases, 508 chronic HBV carriers and 1308 healthy controls at the discovery stage. The associations of HCC risk with these SNPs were further confirmed in an independent case-control set. We found that 1p34.2 rs621559 and 14q21 rs398652 were significantly associated with HBV-related HCC risk (both P<0.005 after Bonferroni corrections). There was no significant difference of either rs621559 or rs398652 genotypes between chronic HBV carriers and healthy controls, demonstrating that the association was not due to predisposition to HBV infection. In the pooled analyses (1806 HBV-related HCC cases and 1954 controls), we observed a decreased HCC risk, 0.72-times, associated with the 1p34.2 rs621559 AA genotype compared to the GG genotype (P = 1.6×10−6). Additionally, there was an increased HCC risk, 1.27-fold, associated with the rs398652 GG genotype (P = 3.3×10−6). A statistical joint effect between the rs621559 GG and rs398652 GG genotypes may exist in elevating risk of HBV-related HCC. We show, for the first time, that rs398652 and rs621559 might be marker genetic variants for risk of HBV-related HCC in the Chinese population.

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Section: Discussionsupporting

confidence: 88%

Section: Resultsmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 85%

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Leukocyte Telomere Length-Related rs621559 and rs398652 Genetic Variants Influence Risk of HBV-Related Hepatocellular Carcinoma

et al. 2014

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“…2 Hospital. Part of these case-control sets and the tissue samples has been reported previously (26)(27)(28). The detailed case-control characteristics are described in the Supplementary Material and Methods, available at Carcinogenesis Online.…”

Section: Study Case-control Setsmentioning

confidence: 99%

The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNAHOTAIRvia a novel intronic enhancer

Zhang¹,

Zhou

et al. 2014

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Long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), which could induce genome-wide retargeting of polycomb-repressive complex 2, trimethylates histone H3 lysine-27 (H3K27me3) and deregulation of multiple downstream genes, is involved in development and progression of esophageal squamous cell carcinoma (ESCC). We hypothesized that the functional single nucleotide polymorphisms (SNP) in HOTAIR may affect HOTAIR expression and/or its function and, thus, ESCC risk. Therefore, we examined the association between three haplotypetagging SNPs (htSNP) across the whole HOTAIR locus and ESCC risk as well as the functional relevance of an ESCC susceptibility SNP rs920778. Genotypes were determined in three independent case-control sets consisted of 2098 ESCC patients and 2150 controls. The allele-specific regulation on HOTAIR expression by the rs920778 SNP was investigated in vitro and in vivo. We found that the HOTAIR rs920778 TT carriers had a 1.37-fold, 1.78-fold and 2.08-fold increased ESCC risk in Jinan, Shijiazhuang and Huaian populations, respectively, compared with the CC carriers (P = 0.003, 7.7 × 10 -4 and 5.9 × 10 -4). During inspecting functional relevance of the rs920778 SNP, we identified a novel intronic HOTAIR enhancer locating between +1719bp and +2353bp from the transcriptional start site through reporter assays. Moreover, there is an allelic regulation of rs920778 on HOTAIR expression via this enhancer in both ESCC cell lines and normal esophageal tissue specimens, with higher HOTAIR expression among T allele carriers. These results demonstrate that functional genetic variants influencing lncRNA regulation may explain a fraction of ESCC genetic basis.

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“…Moreover, in recent clinical studies, it was shown that subjects with a variant allele of rs398652 (associated with longer telomeres) have a significantly reduced risk of developing bladder cancer [13]. In addition, rs398652 genetic variants have an obvious impact on TL and esophageal squamous cell carcinoma susceptibility in Chinese populations [14]. While evidence for the causal role of TL variation in some chronic diseases has accumulated [15], the link between SNPs involved in telomere biology and the risk of hypertension (HTN), CHD, and its risk factors, has not been extensively studied in Korean populations.…”

Section: Introductionmentioning

confidence: 99%

Association between Genetic Variations Affecting Mean Telomere Length and the Prevalence of Hypertension and Coronary Heart Disease in Koreans

et al. 2016

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In this study, we investigated whether the single nucleotide polymorphisms (SNPs) associated with telomere length (TL) were associated with the incidence of hypertension (HTN)/coronary heart disease (CHD) and cardiovascular risk factors in the Korean population. Data from 5,705 (ages 39–70) participants in the Korean Genome Epidemiology Study (rural Ansung and urban Ansan cohorts) were studied. Twelve SNPs known to be associated with telomere biology were tested for an association with HTN/CHD. As results, no significant associations were found between the selected TL-related SNPs and prevalence of HTN and CHD. Among non-alcohol users, subjects with minor alleles in rs1269304 and rs10936601 (TERC and LRRC34, respectively) exhibited a higher rate of CHD occurrence (odds ratio [OR], 1.862; 95% confidence intervals [CIs], 1.137, 3.049; OR, 1.855; 95% CIs, 1.111, 2.985; respectively). However, alcohol users with minor alleles in rs398652 (PELI2) were significantly associated with higher HTN prevalence (OR, 1.179; 95% CIs, 1.040, 1.336). Of the 3 SNPs related to disease outcomes, rs1296304 was significantly associated with increased levels of diastolic blood pressure (β estimate, 0.470; 95% CIs, 0.013, 0.926). The minor allele in rs398652 was significantly associated with higher levels of body mass index (OR, 0.128; 95% CIs, 0.010, 0.246) and γ-glutamyl transpeptidase (OR, 0.013; 95% CIs, 0.001, 0.024). In conclusion, there were no significant associations between the selected TL-related SNPs and the occurrence of HTN/CHD in Koreans. However, the results suggest the presence of a possible interaction between related SNPs and alcohol behavior associated with HTN/CHD occurrence.

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Leukocyte telomere length‐related genetic variants in 1p34.2 and 14q21 loci contribute to the risk of esophageal squamous cell carcinoma

Cited by 25 publications

References 40 publications

Leukocyte Telomere Length-Related rs621559 and rs398652 Genetic Variants Influence Risk of HBV-Related Hepatocellular Carcinoma

Leukocyte Telomere Length-Related rs621559 and rs398652 Genetic Variants Influence Risk of HBV-Related Hepatocellular Carcinoma

The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNAHOTAIRvia a novel intronic enhancer

Association between Genetic Variations Affecting Mean Telomere Length and the Prevalence of Hypertension and Coronary Heart Disease in Koreans

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