• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6681-6686
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• 2013

Background: Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growth factor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis to determine the overall risk of FAEs associated with sorafenib. Methods: Databases, including PubMed, Embase and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies included randomized controlled trials evaluating sorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed according to tumor type and therapy regimen. Results: 13 trials recruiting 5,546 patients were included in our analysis. The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenib had a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of 1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen. A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99; P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs were hemorrhage (8.6%) and thrombus or embolism (4.9%). Conclusions: It is important for health care practitioners to be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4261-4265
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• 2013

Increasing scientific evidence suggests that ribonucleotide reductase M1 (RRM1) may be a powerful predictor of survival in patients with pancreatic cancer treated with adjuvant gemcitabine-based chemotherapy after operative resection, but many existing studies have yielded inconclusive results. This meta-analysis aimed to assess the prognostic role of RRM1 in predicting survival in patients with pancreatic cancer treated with gemcitabine. An extensive literature search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1st, 2013. This meta-analysis was performed using the STATA 12.0 software and crude hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Eight clinical studies were included in this meta-analysis with a total of 665 pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy, including 373 patients in the high RRM1 expression group and 292 patients in the low RRM1 expression group. Our meta-analysis revealed that high RRM1 expression was associated with improved overall survival (OS) of pancreatic cancer patients (HR=1.56, 95%CI=0.95-2.17, P<0.001). High RRM1 expression also was linked to longer disease-free survival (DFS) than low RRM1 expression (HR=1.37, 95%CI=0.25-2.48, P=0.016). In conclusion, our meta-analysis suggests that high RRM1 expression may be associated with improved OS and DFS of pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy. Detection of RRM1 expression may be a promising biomarker for gemcitabine response and prognosis in pancreatic cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5755-5762
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• 2015

Background: Short-course preoperative radiation (SCRT) with delayed surgery was found to increase pathologic complete response (pCR) rates in several trials. However, there was no clear answer on whether SCRT or long-course chemo-radiotherapy (LCRT) is more effective. Therefore we conducted this meta-analysis to evaluate the safety and efficacy of SCRT versus LCRT, both with delayed surgery, for treatment of rectal cancer. Materials and Methods: The literature was searched from PubMed, EMBASE, Web of Science, Cochrane Library and clinicaltrials.gov up to November, 2014. Quality of the randomized controlled trials (RCTs) was evaluated according to the Cochrane's risk of bias tool of RCT. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to rate the level of evidence. Review Manager 5.3 was employed for statistical analysis. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. Results: Three RCTs, with a total of 357 rectal cancer patients, were included in this systematic review. Metaanalysis results demonstrated there were no significantly differences in sphincter preservation rate, local recurrence rate, grade 3~4 acute toxicity, R0 resection rate and downstaging rate. Compared with SCRT, LCRT was associated with significant increase in the pCR rate [RR=0.49, 95%CI (0.31, 0.78), P=0.003]. Conclusions: In terms of sphincter preservation rate, local recurrence rate, grade 3~4 acute toxicity, R0 resection rate and downstaging rate, SCRT with delayed surgery is as effective as LCRT with delayed surgery for management of rectal cancer. LCRT significantly increased pCR rate compared with SCRT. Due to risk of bias and imprecision, further multi-center large sample RCTs were needed to confirm this conclusion.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3417-3422
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• 2012

Objective: Non-homologous end joining (NHEJ) is one of the pathways of repair of DNA double-strand breaks. A number of genes involved in NHEJ have been implicated as breast cancer susceptibility genes such as LIG4. However, some studies have generated conflicting results. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate association between LIG4 gene polymorphisms in the NHEJ pathway and breast cancer risk. Methods: Studies focusing on the relationship between LIG4 gene polymorphisms and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software, calculating odds ratios (ORs) with 95% confidence intervals (95%CIs). Results: According to the inclusion criteria, we final included seven studies with a total of 10,321 breast cancer cases and 10,160 healthy controls in the meta-analysis. The results showed no association between LIG4 gene polymorphisms (rs1805386 T>C, rs1805389 C>T, rs1805388 C>T and rs2232641 A>G) and breast cancer risk, suggesting that the mutant situation of these SNPs neither increased nor decreased the risk for breast cancer. In the subgroup analysis by Hardy-Weinberg equilibrium (HWE) and ethnicity, we also found no associations between the variants of LIG4 gene and breast cancer risk among HWE, non-HWE, Caucasians, Asians and Africans. Conclusion: This meta-analysis suggests that there is a lack of any association between LIG4 gene polymorphisms and the risk of breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3691-3698
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• 2014

Background: Published studies on the association between the Ras Association Domain Family 1 isoform A (RASSF1A) Ala133Ser polymorphism and cancer susceptibility have yielded conflicting results. Thus, a meta-analysis was here performed to assess the possible association. Materials and Methods: All eligible case-control studies published up to November 2013 on the association between RASSF1A Ala133Ser polymorphism and cancer susceptibility were identified by searching PubMed, Web of Science, Science Direct and hand search. Bothfixed-effect and random-effect models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs) by using the Comprehensive Meta-Analysis software version 2.2. Results: A total of 10 studies including 4,572 cancer cases and 4,320 controls were included in the meta-analysis. Overall, significantly increased cancer risk was associated with the variant Ser133 when all studies were pooled (Ser vs Ala: OR=1.51, 95% CI=1.08-2.12, $P_{heterogeneity}{\leq}0.001$; Ser/Ser+Ala/Ser vs Ala/Ala: OR=1.55, 95% CI=1.08-2.22, $P_{heterogeneity}{\leq}0.001$). Moreover, in subgroup analyses by cancer types, a significant association between RASSF1A Ala133Ser polymorphism and lung cancer risk was found (Ser vs Ala: OR=2.27, 95% CI=1.29-4.02, $P_{heterogeneity}$=0.61; Ser/Ser+Ala/Ser vs Ala/Ala: OR=2.42, 95% CI=1.33-4.42, $P_{heterogeneity}=0.75$). In addition, in subgroup analyses by ethnicity, it was found that the RASSF1A Ala133Ser polymorphism was associated with overall cancer risk in Asians (Ser vs Ala: OR=1.37, 95% CI=1.06-1.77, $P_{heterogeneity}=0.06$) and Caucasians (Ser/Ser+Ala/Ser vs Ala/Ala: OR=2.21, 95% CI=1.01-4.82, $P_{heterogeneity}{\leq}0.001$). Conclusions: This meta-analysis suggests, for the first time, that RASSF1A Ala133Ser polymorphism may contribute to cancer susceptibility, especially for lung cancer. Besides, additional well-designed studies with larger sample size focusing on different ethnicities and cancer types are needed to confirm these findings.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3247-3252
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• 2014

Background: Genetic factors have been shown to play an important role in the development of cancers. However, individual studies may fail to completely demonstrate complicated genetic relationships because of small sample size. Therefore, we performed a meta-analysis to evaluate the association of E-selectin Ser128Arg (S128R) with cancer risk. Materials and Methods: A literature search in PubMed, Embase, Web of Science, Science Direct, SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure databases was carried out to identify studies of the association between E-selectin S128R polymorphism and cancer risk. The odds ratio (OR) with 95% confidence intervals (95%CIs) were used to assess the strength of association. Results: A total of eight studies involving 1,675 cancer cases and 2,285 controls were included in the meta-analysis. In overall populations, S128R polymorphism seemed to be associated with cancer risk (Arg allele vs Ser allele: OR=1.65, 95%CI =1.33-2.04, p<0.01; Arg/Arg+Arg/Ser vs Ser/Ser: OR=1.87, 95%CI =1.48-2.36, p<0.01; Arg/Ser vs Ser/Ser: OR=1.80, 95%CI =1.51-2.14, p<0.01). Similarly, subgroup analysis by ethnicity and source of control also revealed that this polymorphism was related to cancer risk. Conclusions: Our meta-analysis revealed that there was association between the E-selectin S128R polymorphism and the risk of cancer. Further large and well-designed studies are needed to confirm this association.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.897-902
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• 2015

PTEN (phosphatase and tensin homologue), as a tumor suppressor gene, plays a significant role in regulating cell growth, proliferation, and apoptosis. Results from published studies for association between the PTEN IVS4 I/D (rs3830675) polymorphism and cancer risk are inconsistent and inconclusive. We therefore conducted a meta-analysis to evaluate the potential association between PTEN IVS4 I/D polymorphism and risk of cancer in detail. We searched PubMed (Medline) and EMBASE web databases to cover all relevant studies published until December 2013. The meta-analysis was carried out and pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were used to appraise the strength of association. A total of 1,993 confirmed cancer cases and 3,200 controls were included from six eligible case-control studies. Results from overall pooled analysis suggested a significant effect of the PTEN IVS4 I/D polymorphism and cancer risk in all genetic models, i.e., allele (I vs D: OR=0.743, 95%CI=0.648 to 0.852, p=0.001), homozygous (II vs DD: OR=0.673, 95%CI=0.555 to 0.816, p=0.001), heterozygous (ID vs DD: OR=0.641, 95%CI=0.489 to 0.840, p=0.001), dominant (II+ID vs DD: OR=0.626, 95%CI=0.489 to 0.802, p=0.001) and recessive (II vs DD+ID: OR=0.749, 95%CI=0.631 to 0.889, p=0.001). Significant publication bias was detected during the analysis. The present meta-analysis suggests that the PTEN IVS4 I/D polymorphism is significantly associated with reduced risk of cancer. However, future larger studies with other groups of populations are warranted to clarify this association.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2025-2029
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• 2012

Objective: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides needed for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lung cancer (LC). So far, several studies between MTHFR C677T polymorphism and LC provide controversial or inconclusive results. Methods: To better assess the purported relationship, we performed a meta-analysis of 14 publications. Eligible studies were identified by searching the Pubmed, Embase, Web of Science and Google Scholar databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Results: Overall, no significant association was detected between the MTHFR C677T polymorphism and LC risk, the same as in race subgroup. However, in the stratified analysis by histological type, significantly increased non-small-cell lung cancer (NSCLC) risk was indicated (T-allele vs. C-allele: OR = 1.11, 95%CI = 1.03-1.19; TT vs. CC: OR = 1.24, 95%CI = 1.09-1.41; TC vs. CC: OR = 1.11, 95%CI = 1.03-1.20 and TT+TC vs. CC: OR = 1.09, 95%CI = 1.03-1.15). At the same time, ever-smokers who carried T-allele (TT+TC) had a 10% decreased LC risk compared with CC genotype carriers. Conclusions: Our study provided evidence that the MTHFR 677T null genotype may increase NSCLC risk, however, it may protect ever-smokers against LC risk. Future studies with large sample sizes are warranted to further evaluate this association in more detail.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4915-4921
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• 2012

Published data on any association between the CYP2E1 RsaI/PstI (c1/c2) polymorphism and liver cancer risk among east Asians are inconclusive. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to derive a more precise estimation of the relationship. A literature search of Pubmed, Embase, Web of science and CBM databases from inception through July 2012 was conducted. Twelve case-control studies were included with a total of 1,552 liver cancer cases and 1,763 healthy controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association under five genetic models. When all the eligible studies were pooled into the meta-analysis, the results showed that the c2 allele and the c2 carrier (c2/c2 + c2/c1) of RsaI/PstI polymorphism were associated with decreased risk of liver cancer among east Asians (c2 vs. c1: OR = 0.75, 95%CI: 0.59-0.95, P = 0.016; c2/c2 + c2/c1 vs. c1/c1: OR = 0.76, 95%CI: 0.58-1.00, P = 0.050). In the stratified analysis by country, significant associations were observed between RsaI/PstI polymorphism and decreased risk of liver cancer among the Chinese population (c2 vs. c1: OR = 0.70, 95%CI: 0.54-0.91, P = 0.007; c2/c2 + c2/c1 vs. c1/c1: OR = 0.72, 95%CI: 0.54-0.95, P = 0.020), but not among Japanese and Korean populations. Results from the current meta-analysis indicates that the c2 allele of CYP2E1 RsaI/PstI (c1/c2) polymorphism may be a protective factor for HCC among east Asians, especially among China populations.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5105-5111
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• 2012

Background: Published data on the association between single nucleotide polymorphisms (SNPs) in the ESR1 gene and breast cancer susceptibility are inconclusive or controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to derive a more precise estimation of this relationship. Methods: A literature search of Pubmed, Embase, Web of science and CBM databases was conducted from inception through September 1th, 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Results: A total of five studies including 1,678 breast cancer cases and 1,678 general population controls in Asian populations were involved in this meta-analysis. When all the eligible studies were pooled into the meta-analysis, the higher transcriptional activity variant allele T of ESR1 PvuII (C>T) (rs2234693) in pre-menopausal breast cancer women showed a significant relation to increased risk (OR = 1.13, 95%CI: 1.01-1.28, P = 0.040) in contrast to their post-menopausal counterparts which showed non-significant increased risk (OR = 1.01, 95%CI: 0.87-1.18, P = 0.858). Nevertheless, no significant association between ESR1 XbaI (A>G) (rs9340799) polymorphism and the risk of breast cancer was observed in pre-menopausal and post-menopausal individuals. Conclusion: Based on a homogeneous Asian population, results from the current meta-analysis indicates that the ESR1 PvuII (C>T) polymorphism places pre-menopausal breast cancer women at risk for breast cancer, while ESR1 XbaI (A>G) polymorphism is not likely to predict the risk of breast cancer.