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ABSTRACT: Gastric cancer is the second leading cause of cancer-related death worldwide with a low 5-year survival (S5y) after initial diagnosis. Although aberrant Wnt/β-catenin (CTNNB1) signaling has been observed in multiple human cancers, there is no information on the role of CTNNB1 polymorphisms in gastric cancer risk and S5y. We performed a genetic association study to analyse the correlation between the five tagged SNPs (tSNPs) (rs4135385, rs1798808, rs1880481, rs11564465 and rs2293303) of CTNNB1 and gastric cancer risk and survival. A total of 944 patients with complete follow-up information and 848 cancer-free controls were enrolled in this study. The rs1880481 polymorphism was correlated with decreased risk of gastric cancer [AC/AA vs. CC: adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.63-0.91], whereas the three other SNPs showed opposite effect (AG/AA vs. GG: adjusted OR = 1.31, 95% CI = 1.08-1.57 for rs4135385; GG vs. AA/AG: 2.09, 1.02-4.28 for rs11564475; TT vs. CC/CT: 4.87, 2.72-8.71 for rs2293303). We further investigated if these tSNPs were related to the S5y of gastric cancer, and the results displayed that only the SNP rs4135385 AG/AA genotypes were significantly associated with a favorable gastric cancer survival compared with the GG genotype [adjusted hazard ratio (HR) = 0.80, 95% CI = 0.66-0.97], and the association was more prominent among patients with non-cardia gastric cancer (NCGC) than those with cardia gastric cancer (CGC) (Log-rank P = 0.007 for NCGC and 0.417 for CGC). Our results indicated that the genetic variants of CTNNB1 could be used as predictors of gastric cancer susceptibility and prognosis.
Mutagenesis 07/2012; · 3.18 Impact Factor
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ABSTRACT: Recent genome-wide association study (GWAS) has identified that the prostate stem cell antigen (PSCA) rs2294008 is involving in regulating gastric epithelial-cell proliferation, influencing the risk of diffuse-type gastric cancer. We hypothesized that PSCA rs2294008 is also associated with gastric cancer survival. We genotyped PSCA rs2294008 using TaqMan method in 943 patients with surgically resected gastric cancer. Analyses of genotype association with survival outcomes were assessed by the Kaplan-Meier method, Cox proportional hazards models and the log-rank test. There was no significant association between rs2294008 and survival of gastric cancer (log-rank p=0.085 for CT/TT versus CC). However, in the stratification analysis of histology, we found that rs2294008 CT/TT genotypes were associated with significantly improved survival among diffuse-type gastric cancer (log-rank p=0.025, hazard ratio [HR]=0.75, 95% confidence interval [CI]=0.59-0.96), compared to the CC genotype. Moreover, this protective effect was more predominant for diffuse-type gastric cancer patients with tumor size >5 cm and distant metastasis. If validated in further studies, PSCA rs2294008 could be useful marker of survival assessment and individualized clinical therapy for gastric cancer, particularly among the diffuse-type gastric cancer.
International Journal of Cancer 11/2010; 129(5):1207-13. · 5.44 Impact Factor
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Na Tong,
Yongjun Fang,
Jie Li,
Meilin Wang,
Qin Lu,
Shizhi Wang, Yuanyuan Tian,
Liucheng Rong,
Jielin Sun,
Jianfeng Xu,
Zhengdong Zhang
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ABSTRACT: Methylenetetrahydrofolate reductase (MTHFR), involved in DNA methylation and nucleotide synthesis, is thought to be associated with a decreased risk of adult and childhood acute lymphoblastic leukemia (ALL). Accumulating evidence has indicated that two common genetic variants, C677T and A1298C, are associated with cancer risk. We hypothesized that these two variants were associated with childhood ALL susceptibility and influence serum MTHFR levels. We genotyped these two polymorphisms and detected MTHFR levels in a case-control study of 361 cases and 508 controls. Compared with the 677CC and 677CC/CT genotypes, the 677TT genotype was associated with a statistically significantly decreased risk of childhood ALL (odds ratio = 0.53, 95% confidence interval = 0.32-0.88, and odds ratio = 0.55, 95% confidence interval = 0.35-0.88, respectively). In addition, a pronounced reduced risk of ALL was observed among low-risk ALL and B-phenotype ALL. Moreover, the mean serum MTHFR level was 8.01 ng/mL (+/-4.38) in cases and 9.27 ng/mL (+/-4.80) in controls (P < 0.001). MTHFR levels in subjects with 677TT genotype was significantly higher than those with 677CC genotype (P = 0.010) or 677CT genotype (P = 0.043) in controls. In conclusion, our results provide evidence that the MTHFR polymorphisms might contribute to reduced childhood ALL risk in this population.
Cancer Science 11/2009; 101(3):782-6. · 3.33 Impact Factor
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ABSTRACT: P53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies revealing conflicting results on the role of p53 codon 72 polymorphism (G>C) on breast cancer risk led us to perform a meta-analysis to investigate this relationship. Thirty-nine published studies, including 26,041 breast cancer cases and 29,679 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. The overall results suggested that the variant genotypes were associated with a significantly reduced breast cancer risk (GC vs. GG: OR = 0.91, 95% CI: 0.83-1.00; CC/GC vs. GG: OR = 0.90, 95% CI: 0.82-0.99). In the stratified analyses, significantly decreased risks were also found among European populations (GC vs. GG: OR = 0.89, 95% CI: 0.80-0.99; CC/GC vs. GG: OR = 0.88, 95% CI: 0.80-0.98) and studies with population-based controls (GC vs. GG: OR = 0.88, 95% CI: 0.78-0.98; CC/GC vs. GG: OR = 0.87, 95% CI: 0.78-0.97). The results suggested that p53 codon 72 polymorphism may contribute to susceptibility to breast cancer, especially in Europeans. Additional well-designed large studies were required to validate this association in different populations.
Breast Cancer Research and Treatment 08/2009; 120(2):509-17. · 4.43 Impact Factor
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ABSTRACT: Caspase-8 (CASP8) is a key regulator of apoptosis or programmed cell death, an essential defense mechanism against hyperproliferation and malignancy. We hypothesized that the variants in the CASP8 gene are associated with risk of bladder cancer.
In a hospital-based case-control study of 365 case patients with newly diagnosed bladder transitional cell carcinoma and 368 cancer-free controls frequency-matched by age and sex, we genotyped the functional -652 6N ins/del polymorphism (rs3834129) in the promoter of CASP8 and assessed its associations with risk of bladder cancer and interaction with tobacco smoking.
A significant decreased risk of bladder cancer was found for the CASP8 -652 6N ins/del (adjusted odds ratio, 0.72; 95% confidence interval, 0.53-0.99) and del/del (odds ratio, 0.37; 95% confidence interval, 0.18-0.77) genotypes. Furthermore, a significant additive interaction between CASP8 polymorphism and tobacco smoking on bladder cancer risk was observed.
These results suggested that the CASP8 -652 6N ins/del polymorphism is involved in etiology of bladder cancer and thus may be a marker for genetic susceptibility to bladder cancer in Chinese populations. Larger studies are warranted to validate our findings.
Clinical Cancer Research 05/2009; 15(7):2567-72. · 7.74 Impact Factor
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ABSTRACT: Runt-related transcription factor 3 (RUNX3) is a well known gene for its functions in gastric cancer suppression, but the effect of its genetic variations on the risk of gastric cancer remains unclear. In this study, ten tagging single nucleotide polymorphisms (tSNPs) of the RUNX3 gene were selected and genotyped in a hospital-based case-control study of 312 gastric cancer patients and 329 cancer-free controls in a Chinese population. In the single-locus analysis, three RUNX3 intronic tSNPs associated with significantly increased risk of gastric cancer were observed: the SNP3 rs11249206 CC genotype (adjusted odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.03-2.99), compared with the TT genotype; the SNP7 rs760805 AA genotype (adjusted OR = 1.82, 95% CI = 1.14-2.92), compared with the TT genotype; and the SNP8 rs2236852 GG genotype (adjusted OR = 1.69, 95% CI = 1.05-2.72), compared with the AA genotype. In the combined analyses of these three tSNPs, we found that the combined genotypes with four to six variant (risk) alleles (i.e. SNP3 C, SNP7 A, and SNP8 G alleles) were associated with an increased risk of gastric cancer compared with those with one to three variant (risk) alleles (adjusted OR = 2.00, 95% CI = 1.41-2.85), and this increased risk was more pronounced among subgroups of age > or =65 years, never smokers, and never drinkers. However, no significant association was observed in the clinicopathological features analyses. In conclusion, the RUNX3 genetic variants may modulate the risk of gastric cancer in a Chinese population. Further larger and functional studies are warranted to validate the findings.
Cancer Science 05/2009; 100(9):1688-94. · 3.33 Impact Factor
