• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.1
• /
• pp.261-267
• /
• 2012

Purpose: The relationship between thymidylate synthase (TS) expression and outcomes in gastric cancer (GC) patients remains controversial, although most studies reported poor survival and reduced response to fluoropyrimidine were related to high TS in tumors. We carried out a systematic review of the literature with meta-analysis to estimate the predictive value of TS expression from published studies. Methods: We indentified 24 studies analysing the outcome data in gastric cancer stratified by TS expression. Effect measures of outcome were hazard ratios (HRs) for overall survival (OS) and event-free survival (EFS), or the odds ratio (OR) for overall response rate (ORR). HRs and ORs from these eligible studies were pooled using random-effects meta-analysis. Results: Fifteen studies investigated outcomes in a total of 844 patients with advanced GC, and nine studies investigated outcomes in a total of 1,235 patients with localized GC undergoing adjuvant therapy. Meta-analysis of estimates showed high TS expression was significantly associated with poor OS in the advanced setting (HR: 1.43, 95%CI: 1.08 - 1.90), and poor EFS in the adjuvant setting (HR: 1.53, 95%CI: 1.01 - 2.32). Subgroup analysis demonstrated TS expression to haves even greater value in predicting OS, EFS and ORR in advanced GC patients treated with fluoropyrimidine monotherapy (HR for OS: 2.32, 95%CI: 1.53 - 3.50; HR for EFS: 1.76, 95%CI: 1.19 - 2.60; OR for ORR: 0.32, 95%CI: 0.11 - 0.95). Conclusion: High levels of TS expression were asssociated with a poorer OS for advanced GC patients compared with low levels. In the adjuvant setting, high TS expression was also associated with a worse EFS. Additional studies with consistent methodology are needed to define the precise predictive value of TS.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.11
• /
• pp.5451-5454
• /
• 2012

Objective: The objective of this study was to evaluate the association of MDR1 gene polymorphisms with susceptibility to hepatocellular carcinoma (HCC). Methods: A total of 689 HCC patients and 680 cancer-free subjects were enrolled. Human MDR1 gene polymorphisms were investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Multiple logistic regression models were applied to estimate the association between MDR1 gene polymorphisms and susceptibility to HCC. Results: We detected a novel c.4125A>C polymorphism and our findings suggested that this variant was significantly associated with susceptibility to HCC. A significantly increased susceptibility to HCC was noted in the homozygote comparison (CC versus AA: OR=1.621, 95% CI 1.143-2.300, ${\chi}^2$=7.4095, P=0.0065), recessive model (CC versus AC+AA: OR=1.625, 95% CI 1.167-2.264, ${\chi}^2$=8.3544, P=0.0039) and allele contrast (C versus A: OR=1.185, 95% CI 1.011-1.389, ${\chi}^2$=4.4046, P=0.0358). However, no significant increase was observed in the heterozygote comparison (AC versus AA: OR=0.995, 95% CI 0.794-1.248, ${\chi}^2$=0.0017, P=0.9672) and dominant model (CC+AC versus AA: OR=1.106, 95% CI 0.894-1.369, ${\chi}^2$=0.8560, P=0.3549). Conclusions: These findings suggest that the c.4125A>C polymorphism of the MDR1 gene might contribute to susceptibility to HCC in the Chinese population. Further work will be necessary to clarify the relationship between the c.4125A>C polymorphism and susceptibility to HCC on larger populations of diverse ethnicity.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.1
• /
• pp.191-194
• /
• 2012

We conducted a case-control study in China to clarify the association between XRCC1-Arg399Gln polymorphism and HCC risk. A total of 150 cases and 158 controls were selected from the the Affiliated Hospital of Qingdao University from May 2008 to May 2010. XRCC1-Arg399Gln polymorphism was based upon duplex polymerase-chain-reaction with the confronting-two-pairprimer (PCR-CTPP) method. All analyses were performed using the STATA statistical package. A significantly increased risk was associated with the Arg/Gln genotype (adjusted OR 1.78, 95%CI=1.13-2.79) compared with genotype Arg/Arg. In contrast, the Gln/Gln genotype had non-significant increased risk of HCC with adjusted OR (95%CI) of 1.69 (0.93-2.66). A significant association was found between positive HBsAg and Arg/Gln, with an OR of 3.43 (95% CI=1.45-8.13). Patients carrying Gln/Gln genotypes showed significantly lower median survival than Arg/Arg genotypes (HR=1.38, 95% CI=1.04-1.84). Further Kaplan-Meier analysis showed decreased median survival in Arg/Gln+Gln/Gln genotype carriers in comparison to Arg/Arg carriers (HR=1.33, 95% CI=1.02-1.76). In conclusion, we observed that XRCC1-Arg399Cln polymorphism is associated with susceptibility to HCC, and XRCC1 Gln allele genotype showed significant prognostic associations.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.19
• /
• pp.8271-8277
• /
• 2014

Aims: Apparent diffusion coefficient (ADC) values of nodes in diffusion-weighted imaging (DWI) are widely used in differentiating metastatic from non-metastatic lymph nodes. The purpose of this meta-analysis was to demonstrate whether DWI could contribute to the precise diagnosis of breast cancer (BC) with and without lymph node metastasis (LNM). Materials and Methods: English and Chinese electronic databases were searched for relevant studies followed by a comprehensive literature search. Two reviewers independently assessed the methodological quality of the included trials based on the quality assessment of diagnostic accuracy studies (QUADAS). Summary odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated. Results: Final analysis of 624 BC subjects (patients with LNM = 254, patients without LNM = 370) were incorporated into the current meta-analysis from 9 eligible cohort studies. Combined ORs of ADCs suggested that ADC values in BC patients without LNM were higher than in patients with LNM (OR=0.56, 95%CI: 0.11-1.01, p=0.015). Subgroup analysis stratified by country indicated a low ADC value in BC patients with LNM rather than those without LNM among Chinese (OR=1.27, 95%CI: 0.89-1.66, p<0.001), Italians (OR=0.75, 95%CI: 0.13-1.38, p=0.018), and Egyptians (OR=1.27, 95%CI: 0.71-1.84, p<0.001). The findings of subgroup analysis by MRI machine type revealed that ADC values from diffusion MRI may be potential diagnostic indicators for BC using Non-Philips 1.5T (OR=1.10, 95%CI: 0.84-1.36, p<0.001). Conclusions: The main findings of our meta-analysis demonstrated that increased signal intensity on DWI and decreased signals on ADC are helpful in diagnosis of BC patients with or without LNM. DWI could therefore be an important imaging investigation in patients suspected of BC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.23
• /
• pp.10175-10179
• /
• 2015

Background: The association between the RTEL1 rs6010620 single nucleotide polymorphism (SNP) and glioma risk has been extensively studied. However, the results remain inconclusive. To further examine this association, we performed a meta-analysis. Materials and Methods: A computerized search of the PubMed and Embase databases for publications regarding the RTEL1 rs6010620 polymorphism and glioma cancer risk was performed. Genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analyses, tests of heterogeneity, cumulative meta-analyses, and assessments of bias were performed in our meta-analysis. Results: Our meta-analysis confirmed that risk with allele A is lower than with allele G for glioma. The A allele of rs6010620 in RTEL1 decreased the risk of developing glioma in the 12 case-control studies for all genetic models: the allele model (OR=0.752, 95%CI: 0.715-0.792), the dominant model (OR=0.729, 95%CI: 0.685-0.776), the recessive model (OR=0.647, 95%CI: 0.569-0.734), the homozygote comparison (OR=0.528, 95%CI: 0.456-0.612), and the heterozygote comparison (OR=0.761, 95%CI: 0.713-0.812). Conclusions: In all genetic models, the association between the RTEL1 rs6010620 polymorphism and glioma risk was significant. This meta-analysis suggests that the RTEL1 rs6010620 polymorphism may be a risk factor for glioma. Further functional studies evaluating this polymorphism and glioma risk are warranted.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.6
• /
• pp.2605-2610
• /
• 2012

Background: Studies investigating the association of 2R/3R polymorphism in the thymidylate synthase 5'-untranslated enhanced region (TSER) and colorectal cancer (CRC) risk have reported conflicting results. Thus, a meta-analysis was performed to summarize the data on the potential association. Methods: Pubmed, Embase and CBM databases were searched for all available studies. Links between the TSER 2R/3R polymorphism and CRC risk were estimated by odds ratios (ORs) with 95% confidence intervals (CIs). Results: Seven case-control studies with a total of 2723 cases and 4030 controls were included in this meta-analysis. The results showed that the 3R variant of TSER 2R/3R polymorphism contributes to CRC risk in two comparison models (OR 3R vs. 2R =1.10, 95%CI 1.02-1.18, P = 0.015; OR Homozygote comparison model = 1.22 1.04-1.43, 95%CI 1.04-1.43, P = 0.012). Subgroup analyses by ethnicity further demonstrated a contribution in Caucasians with three comparison models (OR 3R vs. 2R = 1.10, 95%CI 1.02-1.19, P = 0.015; OR Homozygote comparison model = 1.21, 95%CI 1.03-1.41, P = 0.019; OR Recessive comparison model = 1.18, 95%CI 1.05-1.33, P = 0.008). However, the association in the Asian population was still uncertain due to the limited data (all P values were more than 0.05). Conclusions: Our meta-analysis suggests that the 3R variant of Thymidylate synthase 5'-untranslated enhanced region 2R/3R polymorphism contributes to gastric cancer risk in the Caucasian population, while any association in Asian populations needs further study.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.16
• /
• pp.6923-6928
• /
• 2014

In recent years, mounting evidence has indicated that the CCND1 G870A gene polymorphism, which impacts the mitotic cell cycle, may influence leukemia or non-Hodgkin lymphoma risk. Unfortunately, the previous results were inconsistent. Therefore, a meta-analysis was performed to obtain a more precise estimation of any association. We conducted a search in PubMed, Embase and CNKI covering all published papers up to March, 2014. A total of 9 publications including 10 case-control studies met the inclusion criteria. Odds ratios (ORs) and their 95% confidence intervals (95%CIs) were applied to assess association. The pooled ORs showed significant association in non-Hodgkin lymphoma (comparison A vs G: OR= 1.114, 95%CI=1.053-1.179, p=0.000; homozygote comparison AA vs GG: OR=1.245, 95%CI=1.110-1.396, p=0.000; heterozygote comparison AG vs GG: OR=1.095, 95%CI=1.000-1.199, p=0.05; dominant model AA/GA vs GG: OR=1.137, 95%CI=1.043-1.239, p=0.003; and recessive model AA vs GA/GG: OR=1.177, 95%CI=1.066-1.301, p=0.001). However, there was no association between the CCND1 G870A polymorphism and leukemia risk. In conclusion, the CCND1 G870A polymorphism may increase risk of non-Hodgkin lymphoma, but not leukemia. However, more primary large scale and well-designed studies are still required to evaluate the interaction of CCND1 G870A polymorphism with leukemia and non-Hodgkin lymphoma risk.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.12
• /
• pp.6423-6427
• /
• 2012

Background: Functional single nucleotide polymorphisms of x-ray repair cross-complementing protein 1 (XRCC1) have been suspected to contribute to uterine cervical cancer risk for a long time; however, most previous case-control studies were small sized and biased. Additionally, recent studies suggested that XRCC1 polymorphisms could be a biomarker of response to platinum-based chemotherapy. Methods: A comprehensive search was conducted to retrieve eligible studies and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to measure association strength. Results: A total of 13 studies were identified and analyzed. We found that the Arg194Trp polymorphism (Trp vs. Arg, OR=1.342, 95% CI: 1.176) was associated with increased risk of cervical cancer, while no significant association was found with Arg280His (His vs. Arg, OR=1.059, 95% CI: 0.863, 1.299) or Arg399Gln (Gln vs. Arg, OR=1.144, 95% CI: 0.938, 1.394). As for response to platinum-based chemotherapy, the variant XRCC1 399Gln allele (Gln vs. Arg, OR=0.345, 95% CI: 0.163, 0.729) was linked with a poor response; however, the Arg194Trp polymorphism (TrpArg vs. ArgArg, OR=6.421, 95% CI: 1.573, 26.205) predicted a good response. Conclusion: The Arg194Trp polymorphism of XRCC1 increases risk of cervical cancer; the variant 399Gln allele predicts poor response to platinum-based chemotherapy, while the Arg194Trp polymorphism indicates a good response.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.8
• /
• pp.3943-3947
• /
• 2012

Objective: Findings for associations between the methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and head and neck cancer risk have been conflicting. We therefore performed a meta-analysis to derive a more precise relationship. Methods: Ten published case-control studies were collected and odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR A1298C polymorphism and head and neck cancer risk. Sensitivity analysis and publication bias assessment also were performed to guarantee the statistical power. Results: Overall, no significant association between MTHFR A1298C polymorphism and head and neck cancer risk was found in this meta-analysis (C vs. A: OR=1.04, 95%CI=0.87-1.25, P=0.668, Pheterogeneity<0.001; CC vs. AA: OR=1.07, 95%CI=0.70-1.65, P=0.748, $P_{heterogeneity}<0.001$; AC vs. AA: OR=1.06, 95%CI=0.88-1.27, P=0.565, $P_{heterogeneity}<0.001$; CC+AC vs. AA: OR=1.06, 95%CI=0.86-1.30, P=0.571, $P_{heterogeneity}<0.001$; CC vs. AA+AC: OR=1.02, 95%CI=0.69-1.52, P=0.910, $P_{heterogeneity}<0.001$). Similar results were also been found in succeeding analysis of HWE and stratified analysis of ethnicity. Conclusion: In conclusion, our meta-analysis demonstrates that MTHFR A1298C polymorphism may not be a risk factor for developing head and neck cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.7
• /
• pp.3299-3303
• /
• 2012

Objective: To investigate the association between xeroderma pigmentosum group D (XPD) Asp312Asn polymorphism and esophageal cancer (EC) susceptibility by meta-analysis. Methods: We searched PubMed up to April 9th, 2012, to identify relevant papers, and 8 published case-control studies including 2165 EC patients and 3141 healthy controls were yielded. Odds ratios (ORs) with relevant 95% confidence intervals (CIs) were applied to assess the association between XPD Asp312Asn polymorphism and EC susceptibility with the Comprehensive Meta-Analysis software, version 2.2. Results: Overall, the meta-analysis results suggested the XPD Asp312Asn polymorphism to be significantly associated with EC susceptibility [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.20, 95%CI=1.05-1.36, p=0.01; and Asp/Asn vs. Asp/Asp: OR=1.15, 95%CI =1.01-1.31, p=0.04]. In the subgroup analysis by ethnicity and cancer type, significantly associations were found for Caucasian populations [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.26, 95%CI =1.08-1.47, p<0.001; Asp/Asn vs. Asp/Asp: OR=1.19, 95%CI =1.02-1.40, p=0.03] and esophageal squamous cell carcinoma [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.19, 95%CI=1.01-1.41, p=0.04]. There was no heterogeneity and no publication bias existed. Conclusions: This meta-analysis shows that the XPD Asp312Asn polymorphism may be a risk factor for developing EC, especially for Caucasian populations and esophageal squamous cell carcinoma.