Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy

Jia, Zhifang; Wu, Xing; Cao, Donghui; Wang, Chuan; You, Lili; Jin, Meishan; Wen, Simin; Cao, Xueyuan; Jiang, Jing

doi:10.1155/2016/8578064

Cited by 13 publications

(10 citation statements)

References 34 publications

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“…In addition, we did not find rs2228611 associated with GC, but it was recently reported that patients carrying the mutant genotypes significantly lived longer than those bearing the wild, indicating that rs2228611 might be a positive prognostic marker for GC survival (Jia et al, 2016). …”

Section: Discussioncontrasting

confidence: 77%

DNMT1 , DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis

Liu

et al. 2016

EBioMedicine

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BackgroundIncreasing studies showed that abnormal changes in single nucleotide polymorphisms (SNPs) of DNMTs (DNMT1, DNMT3A and DNMT3B) were associated with occurrence or decrease of various tumors. However, the associations between DNMTs variations and gastric cancer (GC) risk were still conflicting. We aimed to assess the effect of DNMTs polymorphisms on the susceptibility to GC.MethodsFirstly, we did a meta-analysis for 7 SNPs (rs16999593, rs2228611, rs8101866 in DNMT1, rs1550117, rs13420827 in DNMT3A, rs1569686, rs2424913 in DNMT3B). Four genetic models (homozygote, heterozygote, dominant and recessive model) were used. Moreover, a meta-sensitivity and subgroup analysis was performed to clarify heterogeneity source. Lastly, 17 SNPs that couldn't be meta-analyzed were presented in a systematic review.Findings20 studies were included, 13 studies could be meta-analyzed and 7 ones could not. Firstly, a meta-analysis on 13 studies (3959 GC cases and 5992 controls) for 7 SNPs showed that GC risk increased in rs16999593 (heterozygote model: OR 1.36, 95%CI 1.14–1.61; dominant model: OR 1.36, 95%CI 1.15–1.60) and rs1550117 (homozygote model: OR 2.03, 95%CI 1.38–3.00; dominant model: OR 1.20, 95%CI 1.01–1.42; recessive model: OR 1.96, 95%CI 1.33–2.89) but decreased in rs1569686 (dominant model: OR 0.74, 95%CI 0.61–0.90). The remaining SNPs were not found associated with GC risk. Furthermore, the subgroup analysis indicated that for rs1550117 and rs1569686, the significant associations were particularly found in people from Chinese Jiangsu province (rs1550117, OR 1.77, 95%CI 1.25–2.51; rs1569686, OR 0.48, 95%CI 0.36–0.64) and that PCR-RFLP was a sensitive method to discover significant associations (rs1550117, OR 1.77, 95%CI 1.25–2.51; rs1569686, OR 0.49, 95%CI 0.37–0.65). Lastly, a systematic review on 7 studies for 17 SNPs suggested that rs36012910, rs7560488 and rs6087990 might have a potential effect on GC initiation.ConclusionThis meta-analysis demonstrated that rs16999593 and rs1550117 could contribute to GC risk and that rs1569686 might be a protective factor against gastric carcinogenesis. By using these SNPs as biomarkers, it is feasible to estimate the risk of acquiring GC and thus formulate timely preventive strategy.

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Section: Discussioncontrasting

confidence: 77%

DNMT1 , DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis

Liu

et al. 2016

EBioMedicine

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“…Minor alleles of rs2114724 and rs2228611 have been reported to be associated with SZ, gastric, ovarian, and breast cancers, hypertension, and hearing loss [19][20][21][22][23][24]. e results reported here support a significant association of these alleles with SZ.…”

Section: Discussionsupporting

confidence: 70%

Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia

et al. 2021

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A recent study showed the association of minor alleles of rs2228611 (T allele) and rs2114724 (T allele) of DNMT1 with schizophrenia (SZ) and suggested their effects on splicing of the transcripts. We performed a replication study using 310 controls and 304 SZ patients and confirmed the association of the homozygous minor allele genotypes with SZ ( P = 0.04 for rs2114724 and P = 0.007 for rs2228611). This significant association persisted after Bonferroni correction when the previously published data of 301 controls and 325 patients were also considered ( P ≤ 0.0002). In addition, we found that the proportion of male patients with homozygous minor alleles at rs2114724 was significantly higher than that of females ( P = 0.002). When haplotype analysis of both loci was performed, we observed a significant association of T/T–T/T and T/T–C/T ( P = 0.04) haplotypes with SZ. To gain insights into the functional effects of the two SNPs on the levels of DNMT1 transcripts, quantitative real-time PCR experiments were performed using peripheral blood monocytes from 10 individuals each with T/T–T/T (homozygous minor allele), C/T–C/T (heterozygous), and C/C–C/C (homozygous major allele) haplotypes. Independently, the levels of DNMT1 protein were also compared in three individuals each by immunofluorescence. These results suggest that neither DNMT1 transcript nor the protein levels were significantly different in the peripheral blood monocytes among the individuals studied for the three groups. Taken together, our results confirm that the two minor alleles in homozygosity are associated with SZ but with no discernible effects on transcript or protein levels of DNMT1 in the peripheral blood monocytes of the small number of samples tested.

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“…Previous studies have showed that changes in DNA methylation of cancer‐related genes can be an elementary process accounting for tumorigenesis. The polymorphisms of the DNMT1 gene rs2228611 contributes to favorable prognosis in gastric cancer . The DNMT1 rs2228611 and rs759920 SNPs are associated with an increased risk of ovarian cancer development .…”

Section: Discussionmentioning

confidence: 99%

Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival

Wang

et al. 2018

Intl Journal of Cancer

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Cutaneous melanoma (CM) is considered as a steroid hormone-related malignancy. However, few studies have evaluated the roles of genetic variants encoding steroid hormone receptor genes and their related regulators (SHR-related genes) in CM-specific survival (CMSS). Here, we performed a pathway-based analysis to evaluate genetic variants of 191 SHR-related genes in 858 CMSS patients using a dataset from a genome-wide association study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC), and then validated the results in an additional dataset of 409 patients from the Harvard GWAS. Using multivariate Cox proportional hazards regression analysis, we identified three-independent SNPs (RORA rs782917 G > A, RORA rs17204952 C > T and DNMT1 rs7253062 G > A) as predictors of CMSS, with a variant-allele attributed hazards ratio (HR) and 95% confidence interval of 1.62 (1.25-2.09), 1.60 (1.20-2.13) and 1.52 (1.20-1.94), respectively. Combined analysis of risk genotypes of these three SNPs revealed a decreased CMSS in a dose-response manner as the number of risk genotypes increased (p < 0.001); however, no improvement in the prediction model was observed (area under the curve [AUC] = 79.6-80.8%, p = 0.656), when these risk genotypes were added to the model containing clinical variables. Our findings suggest that genetic variants of RORA and DNMT1 may be promising biomarkers for CMSS, but these results needed to be validated in future larger studies.

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Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy

Cited by 13 publications

References 34 publications

DNMT1 , DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis

DNMT1 , DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis

Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia

Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival

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