Zhuoqun Xu

The Effect of hOGG1 Ser326Cys Polymorphism on Cancer Risk: Evidence from a Meta-Analysis

Background Human oxoguanine glycosylase 1 (hOGG1) in base excision repair (BER) pathway plays a vital role in DNA repair. Numerous epidemiological studies have evaluated the association between hOGG1 Ser326Cys polymorphism and the risk of cancer. However, the results of these studies on the association remain conflicting. To derive a more precise estimation of the association, we conducted a meta-analysis. Methodology/Principal Findings A comprehensive search was conducted to identify the eligible studies of hOGG1 Ser326Cys polymorphism and cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. We found that the hOGG1 Ser326Cys polymorphism was significantly associated with overall cancer risk (Cys/Cys vs. Ser/Ser: OR = 1.19, 95%CI = 1.09–1.30, P<0.001; Cys/Cys vs. Cys/Ser+Ser/Ser: OR = 1.16, 95%CI = 1.08–1.26, P<0.001). Moreover, in subgroup analyses by cancer types, the stronger significant association between hOGG1 Ser326Cys polymorphism and lung cancer risk was found (Cys/Cys vs. Ser/Ser: OR = 1.29, 95%CI = 1.16–1.44, P<0.001; Cys/Cys vs. Cys/Ser+Ser/Ser: OR = 1.22, 95%CI = 1.12–1.33, P<0.001). The significant effects of hOGG1 Ser326Cys polymorphism on colorectal, breast, bladder, prostate, esophageal, and gastric cancer were not detected. In addition, in subgroup analyses by ethnicities, we found that the hOGG1 Ser326Cys polymorphism was associated with overall cancer risk in Asians (Cys/Cys vs. Ser/Ser: OR = 1.21, 95%CI = 1.10–1.33, P<0.001). Conclusions This meta-analysis showed that hOGG1 326Cys allele might be a low-penetrant risk factor for lung cancer.

Association of GSTM1 Null Allele with Prostate Cancer Risk: Evidence from 36 Case-Control Studies

Background Glutathione S-transferase M1 (GSTM1) is thought to be involved in detoxifying several carcinogens and may play a vital role in tumorigenesis. Numerous studies have evaluated the association between GSTM1 null/present polymorphism and risk of prostate cancer (PCa). However, the results remain inconsistent. To derive a more precise estimation, we performed a meta-analysis. Methodology/Principal Findings A comprehensive search was conducted to identify all eligible case-control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The overall association was significant (OR = 1.28, 95% CI: 1.11–1.48, P = 0.001). Moreover, subgroup analyses showed GSTM1 null genotype significantly associated with PCa risk among Asians (OR = 1.35, 95% CI: 1.03–1.78, P = 0.03) but not among Caucasians (OR = 1.12, 95% CI: 0.96–1.31, P = 0.16). In addition, we did not find that smoking modified the genotype effect on the risk of PCa. Conclusions/Significance The present meta-analysis suggested that GSTM1 null allele was a low-penetrant risk factor for PCa among Asians.

Genetic variants of the cytochrome P450 and glutathione S-transferase associated with risk of bladder cancer in a south-eastern Chinese population

Objective:  To evaluate the association between genetic polymorphisms of CYP2E1 RsaI and GSTM1 and development of bladder cancer in a south‐eastern Han Chinese population.

Cripto-1 expression and its prognostic value in human bladder cancer patients

Cripto-1 is an important embryonic gene that involved in self-renewal and maintenance of pluripotency of stem cells. Overexpression of Cripto-1 has been found to be correlated with tumorigenesis and may affect tumor recurrence and metastasis. The previous studies indicate that Cripto-1 might be a potential prognostic biomarker for several malignancies. The aim of this study is to examine Cripto-1 expression pattern and clinicopathological significance in human bladder cancer patients. We investigated Cripto-1 expression in 30 paired bladder cancer tissues and corresponding noncancerous bladder tissues using real-time quantitative RT-PCR (qRT-PCR). Moreover, Cripto-1 expression in 130 bladder cancer specimens and bladder cancer T24 and 5637 cells were analyzed using immunohistochemistry and immunofluorescence assays. The recurrence/metastasis-free survival was assessed by Kaplan–Meier method and log-rank test. Cox regression was also used for univariate and multivariate analyses of prognostic factors. The results showed that Cripto-1 expression is increased in bladder cancer tissues and is significantly associated with tumor size (P = 0.005) and tumor grade (P = 0.035). In addition, the expression level of Cripto-1 in bladder cancer was also found to be significantly associated with SRY-related HMG-box gene 2 expression (P = 0.003) and Ki-67 (P = 0.001). Compared with the patients with low Cripto-1 expression, the patients with high Cripto-1 expression had significantly poorer recurrence/metastasis-free survival (P = 0.011). Cox regression showed that Cripto-1 might be an independent prognostic factor for recurrence/metastasis-free survival (P = 0.036). Our findings suggest that high Cripto-1 expression might be involved in the development of bladder cancer and a potentially effective prognostic marker in bladder cancer patients.

GSTP1 Ile105Val Polymorphism and Prostate Cancer Risk: Evidence from a Meta-Analysis

Background Glutathione S-transferase P1 (GSTP1) is thought to be involved in the detoxification of reactive carcinogen metabolites. Numerous epidemiological studies have evaluated the association of GSTP1 Ile105Val polymorphism with the risk of prostate cancer. However, the results remain inconclusive. To derive a more precise estimation, a meta-analysis was performed. Methodology/Principal Findings A comprehensive search was conducted to identify the eligible studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the relationship. The overall association was not significant (Val/Val vs. Ile/Ile OR = 1.06, 95% CI = 0.90–1.25, P = 0.50; Val/Val vs. Val/Ile+Ile/Ile: OR = 1.07, 95% CI = 0.91–1.25, P = 0.44). In subgroup analyses by ethnicity and prostate cancer grade, the similar results were observed. However, in stratified analysis by clinical stage, we found a significant association with low-stage prostate cancer (Val/Val vs. Ile/Ile: OR = 2.70, 95% CI = 1.73–4.22, P<0.001; Val/Val vs. Val/Ile+Ile/Ile: OR = 2.14, 95% CI = 1.38–3.33, P = 0.001). Moreover, there was no statistically significant evidence of multiplicative interactions neither between the GSTP1 Ile105Val polymorphism and GSTM1, nor between smoking status and GSTP1 on prostate cancer risk. Conclusions This meta-analysis showed that GSTP1 Ile105Val polymorphism might not be significantly associated with overall prostate cancer risk. Further stratified analyses showed a significant association with low-stage prostate cancer.

Editorial Comment from Dr Xu and Dr Wei to Murine double minute 2 promoter SNP309 polymorphism and prostate cancer risk: A meta‐analysis

Murine double minute 2 (MDM2) is thought to be a critical negative regulator of p53. It has been suggested that overexpression of MDM2 could lead to inactivation of p53, which might play a vital role in carcinogenesis. It was observed in the study by Leite et al. that overexpression of MDM2 has a role in prostate carcinogenesis, being frequently detected and associated with increased cell proliferation and tumor volume. A single nucleotide polymorphism (SNP) in the MDM2 promoter, SNP309 T>G, has been identified, which might alter MDM2 expression and lead to tumor transformation. In this meta-analysis by Liu et al., the association of MDM2 SNP309 T>G polymorphism with prostate cancer risk was evaluated. Liu et al. found a significant association between MDM2 SNP309 polymorphism and prostate cancer risk. In subgroup analyses, a significant association was also detected in Caucasians. Liu et al. concluded that the MDM2 309G allele might act as a reduced risk factor for prostate cancer. The findings in the meta-analysis were interesting. However, some issues should be addressed regarding the meta-analysis. First, in order to provide a more precise estimation on the basis of adjustment for confounders, well-designed studies are warranted by taking potential confounders into account, such as age and smoking. Further studies are required to investigate the effects of the MDM2 309G allele on familial and sporadic prostate cancer, respectively. Second, quality assessment scores in the meta-analysis were assessed for included studies. According to the more convincing guide in the Cochrane Handbook, the use of scales for assessing quality is explicitly discouraged. Hence, the quality assessment scores for studies included in the meta-analysis should be used cautiously. Third , the MDM2 SNP309 polymorphism should be functionally evaluated in vitro or through knockout or transgene techniques in animals to assess the potential for prostate cancer gene therapy. Collectively, it suggests that the MDM2 309G allele is significantly associated with prostate cancer risk. Further study based on larger sample size is still required, especially in Asians and Africans. If the authors could take into account the aforementioned issues, a more accurate elaboration of the results would be provided.