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Haplotype block map for part of the SNPs in the OBFC1 gene. Darker shades of red indicate higher D' and display statistically significant associations between a pair of SNPs. Rs3814220-rs12765878-rs11191865 block in the figure was found have the linkage disequilibrium, and the D value was 1.
Source publication
Colorectal cancer (CRC) is one of the most common diseases worldwide, and telomere length has been reported correlate with CRC. This study aimed to investigate whether polymorphisms of telomere length related genes are associated with susceptibility to CRC in Chinese Han population. 11 SNPs from TERT, TNIP1 and OBFC1 genes were selected and genotyp...
Context in source publication
Context 1
... we performed haplotype analysis for the TERT, TNIP1 and OBFC1 genes and found 3 strong linkage of these candidate SNPs, containing rs10069690- rs2242652 block in TERT (Figure 1), rs7708392- rs10039748 block in TNIP1 (Figure 2), and rs3814220- rs12765878-rs11191865 block in OBFC1 ( Figure 3). The associations between haplotypes of the 3 blocks and the CRC risk are listed in Table 4. ...
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... Loss-of-function mutations in CTC1 and STN1 cause two complex genetic diseases Coats plus and Dyskeratosis congenita [32][33][34][35][36][37][38] . Moreover, CST has been implicated in tumor development, as STN1 variants are associated with various types of cancer [39][40][41][42][43][44] , and STN1 deficiency promotes colorectal cancer development in young adult mice 45 . We have found that, in response to hydroxyurea (HU) treatment, CTC1 and STN1 proteins localize at stalled forks and inhibit MRE11-mediated NSD after fork reversal. ...
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... Recent TCGA Pan-Cancer analyses show that down-regulation of CST genes is associated with poor outcomes of patients in various cancers, identifying CTC1 and STN1 as the protective factors in several types of cancers (40,41). Similarly, genome-wide association studies analyses have shown that STN1 variants are associated with increased risks of melanoma, leukemia, ovarian, colon, and liver cancers (42)(43)(44)(45)(46)(47). These observations suggest that CTC1 or STN1 may suppress the development of cancers in humans. ...
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... However, the assimilation of available biological information could lead to increased prediction performance of HGIMDA. This method may also act biased toward miRNAs, especially those with several associated disease archives [12,63,64]. ...
Background
Small, non-coding microRNAs, usually of 20–25 nucleotides, are known to regulate the post-transcriptional gene expression, which has a significant role in human biological processes, including immune-biogenesis, homeostasis and infection control as differential expression of such miRNAs is responsible for fine-tuning the organismic development.
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... And they also observed that the haplotype "GC" of rs7708392 and rs10036748 was more frequent among CRC patients and correlated with a 1.58-fold increased CRC susceptibility in Chinese Han population. [27] In this study, we similarly found the two TNIP1 SNPs rs7708392 and rs10036748 were in strong linkage disequilibrium in our subjects and "GC" haplotype of rs7708392 and rs10036748 was significantly associated with increased risk of HCC. Taken together, these data provide support for the notion that TNIP1 polymorphisms might have similar effects on carcinoma risk in same population of China. ...
Study has demonstrated that TNIP1 polymorphisms are associated with an increased risk of HBV-induced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the correlation between polymorphisms in TNIP1 and HCC risk in a Northwest Chinese Han population.
A case–control study was conducted including 473 Hepatocellular carcinoma patients and 564 healthy controls. Three SNPs (rs3792792, rs7708392, and rs10036748) were genotyped with Sequenom MassARRAY technology and their associations with HCC risk were analyzed. These data were evaluated using the Chi-square test/Fisher's exact test, genetic model analysis, and haplotype analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association.
Patients with the “G” allele of TNIP1 rs7708392 showed a significantly increased risk of HCC (OR = 1.24, 95%CI: 1.01–1.52, P = .042). Significant association was also shown between TNIP1 rs7708392 and HCC susceptibility in Additive model (OR = 1.25; 95% CI = 1.01–1.54; P = .040). Besides, we also found that the “GC” haplotype of rs7708392 and rs10036748 was significantly associated with higher occurrence of HCC (OR = 1.25, 95% CI: 1.01–1.54, P = .039).
These results demonstrate that TNIP1 polymorphisms are associated with increased HCC risk in a Northwest Chinese Han population for the first time, which warrants further investigation in the future.
... Thus, CST dysregulation might be linked to carcinogenesis and/or clinical response to radiotherapy and chemotherapy. Indeed, genetic variants of STN1 and STN1 downregulation are associated with a number of cancers including epithelial ovarian cancer, colorectal cancer, leukemia, thyroid cancer, melanoma, and uterine cancer [106][107][108][109][110][111]. In addition, higher expression of CTC1 and STN1 appears to correlate with better disease-free survival in breast cancer patients [25,112]. ...
The human CST (CTC1-STN1-TEN1) complex is an RPA-like single-stranded DNA binding protein complex. While its telomeric functions have been well investigated, numerous studies have revealed that hCST also plays important roles in maintaining genome stability beyond telomeres. Here, we review and discuss recent discoveries on CST in various global genome maintenance pathways, including findings on the CST supercomplex structure, its functions in unperturbed DNA replication, stalled replication, double-strand break repair, and the ATR-CHK1 activation pathway. By summarizing these recent discoveries, we hope to offer new insights into genome maintenance mechanisms and the pathogenesis of CST mutation-associated diseases.
... 19,20 The TNIP1 (TNFAIP3 interacting protein 1) gene plays an important role in the immune system and homeostasis by regulating nuclear transcription factor κB activation and is related to telomere length. 21,22 The OBFC1 (oligonucleotide/oligosaccharide-binding foldcontaining protein 1) gene protects the telomere structure from degradation, maintains telomere length and participates in DNA metabolism. [22][23][24] The MPHOSPH6 (m-phase phosphoprotein 6) gene, which encodes for a RNA-binding protein, participates in the synthesis of 5.8s ribosomal rRNA from a 7S ribosomal precursor, plays a role in the recruitment of ribosomal precursor and is also related to telomere length. ...
... 21,22 The OBFC1 (oligonucleotide/oligosaccharide-binding foldcontaining protein 1) gene protects the telomere structure from degradation, maintains telomere length and participates in DNA metabolism. [22][23][24] The MPHOSPH6 (m-phase phosphoprotein 6) gene, which encodes for a RNA-binding protein, participates in the synthesis of 5.8s ribosomal rRNA from a 7S ribosomal precursor, plays a role in the recruitment of ribosomal precursor and is also related to telomere length. 25,26 The ZNF208 (zinc finger protein 208) gene, which is located on chromosome 19 (19p12), regulates gene transcription by binding downstream genes and maintains telomere length. ...
Background
Single nucleotide polymorphisms (SNPs) in telomere-related genes are associated with a high risk of hepatocellular carcinoma (HCC). In this study, we investigated the SNPs of telomere length-related genes and their correlation with HCC risk in the Chinese Han population.
Materials and methods
A total of 473 HCC patients and 564 healthy volunteers were recruited. Overall, 42 SNPs distributed in telomere-related genes were selected and identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.
Results
We found rs6713088 (OR = 1.27, 95% CI = 1.07–1.52, p = 0.007), rs843711 (OR = 1.29, 95% CI = 1.09–1.54, p = 0.004) and rs843706 (OR = 1.30, 95% CI = 1.09–1.55, p = 0.003) in the ACYP2 gene, rs10936599 (OR = 1.21, 95% CI = 1.02–1.44, p = 0.032) in the TERC gene and rs7708392 (OR = 1.24, 95% CI = 1.00–1.52, p = 0.042) in the TNIP1 gene were associated with high HCC risk (OR > 1). In contrast, rs1682111 (OR = 0.77, 95% CI = 0.64–0.94, p = 0.008) in the ACYP2 gene, rs2320615 (OR = 0.79, 95% CI = 0.64–0.99, p = 0.038) in the NAF1 gene, rs10069690 (OR = 0.75, 95% CI = 0.59–0.96, p = 0.021) and rs2242652 (OR = 0.70, 95% CI = 0.55–0.90, p = 0.004) in the TERT gene were associated with low HCC risk (OR < 1). Based on genotype frequency distributions, rs6713088, rs843645, rs843711 and rs843706 located in the ACYP2 gene as well as rs10936599 in the TERC gene were associated with a high incidence of HCC ( p < 0.05). In addition, SNPs in these genes could form a linkage imbalance haplotype. Specifically, the haploid ‘GC’ formed by rs10069690 and rs2242652 within the TERT gene increased the risk of HCC ( p < 0.05).
Conclusion
SNPs in ACYP2, TERC, TERT and other genes were correlated with HCC risk in the Chinese Han population. These data may provide new insights into early diagnosis and screening of HCC.
