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Clinical significance of MYT1L gene polymorphisms in Chinese patients with gastric cancer.

Zhang Y, Zhu H, Zhang X, Gu D, Zhou X, Wang M, Cao C, Zhang X, Wu X, Gong W, Tang Y, Zhou J, Tang C, Zhang Z, Chen J - PLoS ONE (2013)

Bottom Line: There are evidences from several cytology experiments showing that MYT1 is associated with carcinoma.Multivariate Cox regression analyses showed that the AG/GG genotypes were associated with a significantly decreased risk of death from gastric cancer (adjusted hazard ratio (HR) = 0.57, 95% confidence interval (CI) = 0.40-0.81).Further validation in other larger studies with different ethnic populations and functional evaluations are needed.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China ; Department of Oncology, Xuzhou Central Hospital, Affiliated Xuzhou Hospital, College of Medicine, Southeast University, Xuzhou, Nanjing.

ABSTRACT

Background: Myelin transcription factor 1 (MYT1) and its homologue MYT1-like (MYT1L) are the two main members of MYT/NZF family transcription factors, which are highly related, share a high degree of identity and show similar regulatory functions in neural development. There are evidences from several cytology experiments showing that MYT1 is associated with carcinoma.

Methodology/principal findings: In the present study, we genotyped 944 surgically resected gastric cancer patients by the SNaPshot method to explore the association of MYT1L rs17039396 polymorphism with survival of gastric cancer in a Chinese population. We found that cardia cancer patients carrying MYT1L rs17039396 GG genotype survived for a significantly shorter time than those carrying the GA genotype. This significance was enhanced in the dominant model (GG vs. GA/AA, log-rank P = 0.001), suggesting a potential protect role of the variant A allele. Multivariate Cox regression analyses showed that the AG/GG genotypes were associated with a significantly decreased risk of death from gastric cancer (adjusted hazard ratio (HR) = 0.57, 95% confidence interval (CI) = 0.40-0.81). Stratification analyses further showed that such protective effect was statistically significant in subgroups of patients with tumor size ≤5 cm (adjusted HR = 0.34, 95%CI = 0.19-0.64), well-moderate gastric cancer (adjusted HR = 0.59, 95%CI = 0.35-0.98), no lymph-node metastasis (adjusted HR = 0.49, 95%CI = 0.31-0.76), no distant metastasis (adjusted HR = 0.59, 95%CI = 0.41-0.84).

Conclusions/significance: In conclusion, these data represents the first demonstration that MYT1L rs17039396 variants could indentified as a favorable prognostic indicator for gastric cancer, particularly among the cardia gastric cancer. Further validation in other larger studies with different ethnic populations and functional evaluations are needed.

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Overall survival curve in relation to MYT1L rs17039396 polymorphism in patients with cardia gastric cancer in dominant model.Figure 2 represents the Kaplan-Meier survival curve in relation to the effect of MYT1L rs17039396 polymorphism on overall survival of the patients with cardia gastric cancer in dominant model. Patients with GA or AA genotypes was at lower risk of death, compared with those with GG homozygotes. P value is 0.001, suggesting that MYT1L rs17039396 GA+AA genotypes were associated with better overall survival in 309 patients with cardia gastric cancer.
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pone-0071979-g002: Overall survival curve in relation to MYT1L rs17039396 polymorphism in patients with cardia gastric cancer in dominant model.Figure 2 represents the Kaplan-Meier survival curve in relation to the effect of MYT1L rs17039396 polymorphism on overall survival of the patients with cardia gastric cancer in dominant model. Patients with GA or AA genotypes was at lower risk of death, compared with those with GG homozygotes. P value is 0.001, suggesting that MYT1L rs17039396 GA+AA genotypes were associated with better overall survival in 309 patients with cardia gastric cancer.

Mentions: Among 944 specimens of GC patients, MYT1L rs17039396 was successfully genotyped in 909 specimens. The frequency of each genotypes was 57.0% (518 specimens) for the GG variant, 37.8% (344 specimens) for the GA variant, and 5.2% (47 specimens) for the AA variant. The genotype frequencies of MYT1L rs17039396 in the cases followed HWE (P = 0.21). The Kaplan-Meier survival analysis and Cox proportional hazard models were used to assess the prognostic effect of MYT1L rs17039396 on GC patients in different genetic models (Table 2). No significant associations were observed between the MYT1L rs17039396 genotypes and OS of GC patients in any genetic models. We further evaluated the associations by stratified analysis of tumor location and histological types. In the overall model, MYT1L rs17039396 polymorphism was associated with the survival of cardia cancer (log-rank P = 0.015, Fig. 1). Survival time of patients with the GA genotype (MST 98 months) was significantly different compared with that of patients with the GG genotype (MST 47 months), who had a 44% higher risk of death (HR = 0.56, 95% CI = 0.39–0.81). In the dominant model, a significantly lower risk of death (HR = 0.57, 95% CI = 0.40–0.81) was found (log-rank P = 0.001), as shown in Fig. 2.


Clinical significance of MYT1L gene polymorphisms in Chinese patients with gastric cancer.

Zhang Y, Zhu H, Zhang X, Gu D, Zhou X, Wang M, Cao C, Zhang X, Wu X, Gong W, Tang Y, Zhou J, Tang C, Zhang Z, Chen J - PLoS ONE (2013)

Overall survival curve in relation to MYT1L rs17039396 polymorphism in patients with cardia gastric cancer in dominant model.Figure 2 represents the Kaplan-Meier survival curve in relation to the effect of MYT1L rs17039396 polymorphism on overall survival of the patients with cardia gastric cancer in dominant model. Patients with GA or AA genotypes was at lower risk of death, compared with those with GG homozygotes. P value is 0.001, suggesting that MYT1L rs17039396 GA+AA genotypes were associated with better overall survival in 309 patients with cardia gastric cancer.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756043&req=5

pone-0071979-g002: Overall survival curve in relation to MYT1L rs17039396 polymorphism in patients with cardia gastric cancer in dominant model.Figure 2 represents the Kaplan-Meier survival curve in relation to the effect of MYT1L rs17039396 polymorphism on overall survival of the patients with cardia gastric cancer in dominant model. Patients with GA or AA genotypes was at lower risk of death, compared with those with GG homozygotes. P value is 0.001, suggesting that MYT1L rs17039396 GA+AA genotypes were associated with better overall survival in 309 patients with cardia gastric cancer.
Mentions: Among 944 specimens of GC patients, MYT1L rs17039396 was successfully genotyped in 909 specimens. The frequency of each genotypes was 57.0% (518 specimens) for the GG variant, 37.8% (344 specimens) for the GA variant, and 5.2% (47 specimens) for the AA variant. The genotype frequencies of MYT1L rs17039396 in the cases followed HWE (P = 0.21). The Kaplan-Meier survival analysis and Cox proportional hazard models were used to assess the prognostic effect of MYT1L rs17039396 on GC patients in different genetic models (Table 2). No significant associations were observed between the MYT1L rs17039396 genotypes and OS of GC patients in any genetic models. We further evaluated the associations by stratified analysis of tumor location and histological types. In the overall model, MYT1L rs17039396 polymorphism was associated with the survival of cardia cancer (log-rank P = 0.015, Fig. 1). Survival time of patients with the GA genotype (MST 98 months) was significantly different compared with that of patients with the GG genotype (MST 47 months), who had a 44% higher risk of death (HR = 0.56, 95% CI = 0.39–0.81). In the dominant model, a significantly lower risk of death (HR = 0.57, 95% CI = 0.40–0.81) was found (log-rank P = 0.001), as shown in Fig. 2.

Bottom Line: There are evidences from several cytology experiments showing that MYT1 is associated with carcinoma.Multivariate Cox regression analyses showed that the AG/GG genotypes were associated with a significantly decreased risk of death from gastric cancer (adjusted hazard ratio (HR) = 0.57, 95% confidence interval (CI) = 0.40-0.81).Further validation in other larger studies with different ethnic populations and functional evaluations are needed.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China ; Department of Oncology, Xuzhou Central Hospital, Affiliated Xuzhou Hospital, College of Medicine, Southeast University, Xuzhou, Nanjing.

ABSTRACT

Background: Myelin transcription factor 1 (MYT1) and its homologue MYT1-like (MYT1L) are the two main members of MYT/NZF family transcription factors, which are highly related, share a high degree of identity and show similar regulatory functions in neural development. There are evidences from several cytology experiments showing that MYT1 is associated with carcinoma.

Methodology/principal findings: In the present study, we genotyped 944 surgically resected gastric cancer patients by the SNaPshot method to explore the association of MYT1L rs17039396 polymorphism with survival of gastric cancer in a Chinese population. We found that cardia cancer patients carrying MYT1L rs17039396 GG genotype survived for a significantly shorter time than those carrying the GA genotype. This significance was enhanced in the dominant model (GG vs. GA/AA, log-rank P = 0.001), suggesting a potential protect role of the variant A allele. Multivariate Cox regression analyses showed that the AG/GG genotypes were associated with a significantly decreased risk of death from gastric cancer (adjusted hazard ratio (HR) = 0.57, 95% confidence interval (CI) = 0.40-0.81). Stratification analyses further showed that such protective effect was statistically significant in subgroups of patients with tumor size ≤5 cm (adjusted HR = 0.34, 95%CI = 0.19-0.64), well-moderate gastric cancer (adjusted HR = 0.59, 95%CI = 0.35-0.98), no lymph-node metastasis (adjusted HR = 0.49, 95%CI = 0.31-0.76), no distant metastasis (adjusted HR = 0.59, 95%CI = 0.41-0.84).

Conclusions/significance: In conclusion, these data represents the first demonstration that MYT1L rs17039396 variants could indentified as a favorable prognostic indicator for gastric cancer, particularly among the cardia gastric cancer. Further validation in other larger studies with different ethnic populations and functional evaluations are needed.

Show MeSH
Related in: MedlinePlus