Meta-analysis of Association Studies of CYP1A1 Genetic Polymorphisms with Digestive Tract Cancers Susceptibility in Chinese

Liu, Chang,Jiang, Zheng,Deng, Qian-xi,Zhao, Ya-nan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Background: A great number of studies have shown that cytochrome P450 1A1 (CYP1A1) genetic polymorphisms, CYP1A1 Msp I and CYP1A1 Ile/Val, might be risk factors for digestive tract cancers, including esophageal cancer (EC), gastric cancer (GC), hepatic carcinoma (HC), as well as colorectal cancer (CC), but the results are controversial. In this study, a meta-analysis of this literature aimed to clarify associations of CYP1A1 genetic polymorphisms with digestive tract cancers susceptibility in Chinese populations. Materials and Methods: Eligible case-control studies published until December 2013 were retrieved by systematic literature searches from PubMed, Embase, CBM, CNKI and other Chinese databases by two investigators independently. The associated literature was acquired through deliberate search and selection based on established inclusion criteria. Fixed-effects or random-effects models were used to estimate odds ratios (ORs and 95%CIs). The meta-analysis was conducted using Review Manager 5.2 and Stata 12.0 softwares with stability evaluated by both stratified and sensitivity analyses. Moreover, sensitivity analysis and publication bias diagnostics confirmed the reliability and stability. Results: Eighteen case-control studies with 1,747 cases and 2,923 controls were selected for CYP1A1 MspI polymorphisms, and twenty case-control studies with 3, 790 cases and 4, 907 controls for the CYP1A1 Ile/Val polymorphisms. Correlation associations between CYP1A1 Ile/Val polymorphisms and digestive tract cancers susceptibility were observed in four genetic models in the meta-analysis (GG vs AA:OR= 2.03, 95%CI =1.52- 2.72; AG vs AA: OR=1.26, 95%CI =1.07-1.48; [GG+AG vs AA] :OR =1.42, 95%CI=1.20-1.68, [GG vs AA+AG]:OR=1.80, 95%CI =1.40-2.31). There was no association between CYP1A1 Msp I polymorphisms and digestive tract cancers risk. Subgroup analysis for tumor type showed a significant association of CYP1A1 Ile/Val genetic polymorphisms with EC in China. However, available data collected by the study failed to reveal remarkable associations of GC or HC with CYP1A1 Ile/Val genetic polymorphisms and EC, GC or CC with CYP1A1 MspI genetic polymorphisms. Conclusions: Our results indicated that CYP1A1 Ile/Val genetic polymorphisms, but not CYP1A1 Msp I polymorphisms, are associated with an increased digestive tract cancers risk in Chinese populations. Additional well-designed studies, with larger sample size, focusing on different ethnicities and cancer types are now warranted to validate this finding.

Meta-analysis of Associations between ATM Asp1853Asn and TP53 Arg72Pro Polymorphisms and Adverse Effects of Cancer Radiotherapy

Su, Meng,Yin, Zhi-Hua,Wu, Wei,Li, Xue-Lian,Zhou, Bao-Sen Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: The ataxia telangiectasia mutated (ATM) protein and p53 play key roles in sensing and repairing radiation-induced DNA double strand breaks (DSBs). Accumulating epidemiological evidence indicates that functional genetic variants in ATM and TP53 genes may have an impact on the risk of radiotherapy-induced side effects. Here we performed a meta-analysis to investigate the potential interaction between ATM Asp1853Asn and TP53 polymorphisms and risk of radiotherapy-induced adverse effects quantitatively. Materials and Methods: Relevant articles were retrieved from PubMed, ISI Web of Science and the China National Knowledge Infrastructure (CNKI) databases. Eligible studies were selected according to specific inclusion and exclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled to estimate the association between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and risk of radiotherapy adverse effects. All analyses were performed using the Stata software. Results: A total of twenty articles were included in the present analysis. In the overall analysis, no significant associations between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and the risk of radiotherapy adverse effects were found. We conducted subgroup analysis stratified by type of cancer, region and time of appearance of side effects subsequently. No significant association between ATM Asp1853Asn and risk of radiotherapy adverse effects was found in any subgroup analysis. For TP53 Arg72Pro, variant C allele was associated with decreased radiotherapy adverse effects risk among Asian cancer patients in the stratified analysis by region (OR=0.71, 95%CI: 0.54-0.93, p=0.012). No significant results were found in the subgroup analysis of tumor type and time of appearance of side effects. Conclusions: The TP53 Arg72Pro C allele might be a protective factor of radiotherapy-induced adverse effects among cancer patients from Asia. Further studies that take into consideration treatment-related factors and patient lifestyle including environmental exposures are warranted.

Meta-Analysis of the Association between H63D and C282Y Polymorphisms in HFE and Cancer Risk

Zhang, Meng,Xiong, Hu,Fang, Lu,Lu, Wei,Wu, Xun,Wang, Yong-Qiang,Cai, Zhi-Ming,Wu, Song Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.11

Background: Previous studies suggested that the H63D and C282Y polymorphisms in the HFE genes were susceptible to many cancer types, nevertheless, the present results were inconclusive. Thus, the present study was aimed to evaluate the association between the HFE polymorphisms (H63D and C282Y) and cancer risk via meta-analysis. Materials and Methods: We retrieved PubMed, Google Scholar, Embase and Web of Science databases for all eligible studies up to April 1, 2015. All the statistical analysis was conducted by STATA 12.0. Results: Finally, a total of 20 publications including 24 case-control studies, comprising 6,524 cases and 31,080 controls for HFE-C282Y polymorphism and 19 publications including 21 case control studies, comprising 5,648 cases and 14,257 controls for HFE-H63D polymorphism were enrolled in our analysis. An increased risk for overall cancer risk was identified in HFE-H63D polymorphism under allele contrast (D vs H: OR=1.153; 95%CI=1.031-1.289, Pheterogeneity=0.002), homozygotes vs wide type (DD vs HH: OR=1.449; 95%CI=1.182-1.777, Pheterogeneity=0.391), dominant model (DD+HD vs HH: OR=1.145; 95%CI=1.007-1.301, Pheterogeneity=0.002) and recessive model (DD vs HD+HH: OR=1.416 ; 95%CI=1.156-1.735, Pheterogeneity=0.549), as well as HFE-C282Y under homozygotes vs wide type (YY vs CC: OR=1.428, 95%CI=1.017-2.006, Pheterogeneity=0.220). In addition, in the stratified analysis by cancer type, an increased risk was identified in hepatocellular carcinoma and breast cancer in C282Y polymorphism, as well as pancreatic cancer in H63D polymorphism, whereas a decreased risk of colorectal cancer was identified in C282Y polymorphism. Conclusions: Present study suggested that H63D and C282Y polymorphisms associated with an increased risk of overall cancer. Nevertheless, well-designed study with large sample size will be continued on this issue of interest.

Matrix Metalloproteinase-2 -1306 C>T Gene Polymorphism is Associated with Reduced Risk of Cancer: a Meta-analysis

Haque, Shafiul,Akhter, Naseem,Lohani, Mohtashim,Ali, Arif,Mandal, Raju K. Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Matrix metalloproteinase-2 (MMP2) is an endopeptidase, mainly responsible for degradation of extracellular matrix components, which plays an important role in cancer disease. A single nucleotide polymorphism (SNP) at -1306 disrupts a Sp1-type promoter site. The results from the published studies on the association between MMP2 -1306 C>T polymorphism and cancer risk are contradictory and inconclusive. In the present study, a meta-analysis was therefore performed to evaluate the strength of any association between the MMP2 -1306 C>T polymorphism and risk of cancer. We searched all eligible studies published on association between MMP2 -1306 C>T polymorphism and cancer risk in PubMed (Medline), EMBASE and Google Scholar online web databases until December 2013. Genotype distribution data were collected to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) to examine the strength of the association. A total of 8,590 cancer cases and 9,601 controls were included from twenty nine eligible case control studies. Overall pooled analysis suggested significantly reduced risk associated with heterozygous genotype (CT vs CC: OR=0.758, 95%CI=0.637 to 0.902, p=0.002) and dominant model (TT+CT vs CC: OR=0.816, 95%CI=0.678 to 0.982, p=0.032) genetic models. However, allelic (T vs C: OR=0.882, 95%CI=0.738 to 1.055, p=0.169), homozygous (TT vs CC: OR=1.185, 95%CI=0.825 to 1.700, p=0.358) and recessive (TT vs CC+CT: OR=1.268, 95%CI=0.897 to 1.793, p=0.179) models did not show any risk. No evidence of publication bias was detected during the analysis. The results of present meta-analysis suggest that the MMP2 -1306 C>T polymorphism is significantly associated with reduced risk of cancer. However, further studies with consideration of different populations will be required to evaluate this relationship in more detail.

Association of the PTEN IVS4 (rs3830675) Gene Polymorphism with Reduced Risk of Cancer: Evidence from a Meta-analysis

Mandal, Raju K.,Akhter, Naseem,Irshad, Mohammad,Panda, Aditya K.,Ali, Arif,Haque, Shafiul Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

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.

No Association of the TGF-β1 29T/C Polymorphism with Breast Cancer Risk in Caucasian and Asian Populations: Evidence from a Meta-Analysis Involving 55, 841 Subjects

Alqumber, Mohammed A.A.,Dar, Sajad Ahmad,Haque, Shafiul,Wahid, Mohd,Singh, Rohit,Akhter, Naseem Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

The transforming growth factor-${\beta}1$ (TGF-${\beta}1$) gene 29 T/C polymorphism is thought to be associated with breast cancer risk. However, reports are largely conflicting and underpowered. We therefore conducted a meta-analysis of all available case-control studies relating the TGF-${\beta}1$ 29T/C polymorphism to the risk of developing breast cancer by including a total of 31 articles involving 24,021 cases and 31,820 controls. Pooled ORs were generated for the allele contrasts, with additive genetic, dominant genetic and recessive genetic models. Subgroup analysis was also performed by ethnicity for the TGF-${\beta}1$ 29T/C polymorphism. No association was found in the overall analysis (C vs T: OR=1.028, 95% CI=0.949-1.114, p-value 0.500; CC vs TC: OR= 1.022, 95% CI=0.963-1.085, p-value 0.478; CC vs TT: OR= 1.054, 95% CI=0.898-1.236, p-value 0.522; CC vs TT+ TC: OR= 1.031, 95% CI=0.946-1.124, p-value 0.482; TT vs CC+TC: OR= 0.945, 95% CI=0.827-1.080, p-value 0.403). Similarly, in the subgroup analysis by ethnicity, no association was found in Caucasian (C vs T: OR= 1.041, 95% CI=0.932-1.162, p-value 0.475; CC vs TC: OR= 1.031, 95% CI=0.951-1.118, p-value 0.464; CC vs TT: OR= 1.081, 95% CI=0.865-1.351, p-value 0.493; CC vs TT+TC: OR= 1.047, 95% CI=0.929-1.180, p-value 0.453; TT vs CC+TC: OR= 0.929, 95% CI=0.775-1.114, p-value 0.429;) and Asian populations (C vs T: OR= 1.004, 95% CI=0.908-1.111, p-value 0.931; CC vs TC: OR= 0.991, 95% CI=0.896-1.097, p-value 0.865; CC vs TT: OR= 1.015, 95% CI=0.848-1.214, p-value 0.871; CC vs TT+TC: OR= 1.000, 95% CI=0.909-1.101, p-value 0.994; TT vs CC+TC: OR= 0.967, 95% CI=0.808-1.159, p-value 0.720;). No evidence of publication bias was detected during the analysis. No significant association with breast cancer risk was demonstrated overall or on subgroup (Caucasian and Asian) analysis. It can be concluded that TGF-${\beta}1$ 29T/C polymorphism does not play a role in breast cancer susceptibility in overall or ethnicity-specific manner.

N-Acetyltransferase 2 Gene Polymorphisms are Associated with Susceptibility to Cancer: a Meta-analysis

Tian, Fang-Shuo,Shen, Li,Ren, Yang-Wu,Zhang, Yue,Yin, Zhi-Hua,Zhou, Bao-Sen Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

N-acetyltransferase 2 (NAT2) is a polymorphic enzyme that plays an important role in the metabolism of various potential carcinogens. In recent years, a number of studies have been carried out to investigate the relationship between the rs1799930 and rs1799931 polymorphism in NAT2 and cancer risk in multiple populations for different types of cancer. However, the results were not consistent. Therefore, we performed a meta-analysis to further explore the relationship between NAT2 polymorphism and the risk of cancer. A total of 21 studies involving 15, 450 subjects for rs1799930 and 13, 011 subjects for rs1799931 were included in this meta-analysis. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of associations. We also evaluated the publication bias and performed a sensitivity analysis. Overall, our results showed an apparent significant association between the NAT2 rs1799930 polymorphism and cancer susceptibility in Asians (GA vs. GG: OR=1.22, 95% CI=1.03-1.45; dominant model: OR=1.22, 95% CI=1.03-1.43) and population-based controls (GA vs. GG: OR=1.10, 95% CI=1.01-1.19; dominant model: OR=1.09, 95% CI=1.01-1.18). In contrast, a significant association was observed between the NAT2 rs1799931 G>A polymorphism and decreased cancer susceptibility in overall meta-analysis (AA vs. GG: OR=0.55, 95% CI=0.33-0.93; GA vs. GG: OR=1.00, 95% CI=0.88-1.14; dominant model: OR=0.97, 95% CI=0.86-1.10; recessive model: OR=0.56, 95% CI=0.34-0.94) and the Asian group (AA vs. GG: OR=0.50, 95% CI=0.26-0.94; recessive model, OR=0.50, 95% CI=0.27-0.94). We found that the NAT2 rs1799930 may be a risk factor, while the NAT2 rs1799931 polymorphism is associated with a decreased risk of cancer and is likely a protective factor against cancer development.

Four Polymorphisms in the Cytochrome P450 1A2 (CYP1A2) Gene and Lung Cancer Risk: a Meta-analysis

Bu, Zhi-Bin,Ye, Meng,Cheng, Yun,Wu, Wan-Zhen Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Background: Previous published data on the association between CYP1A2 rs762551, rs2069514, rs2069526, and rs2470890 polymorphisms and lung cancer risk have not allowed a definite conclusion. The present meta-analysis of the literature was performed to derive a more precise estimation of the relationship. Materials and Methods: 8 publications covering 23 studies were selected for this meta-analysis, including 1,665 cases and 2,383 controls for CYP1A2 rs762551 (from 8 studies), 1,456 cases and 1,792 controls for CYP1A2 rs2069514 (from 7 studies), 657 cases and 984 controls for CYP1A2 rs2069526 (from 5 studies) and 691 cases and 968 controls for CYP1A2 rs2470890 (from 3 studies). Results: When all the eligible studies were pooled into the meta-analysis for the CYP1A2 rs762551 polymorphism, significantly increased lung cancer risk was observed in the dominant model (OR=1.21, 95 % CI=1.00-1.46). In the subgroup analysis by ethnicity, significantly increased risk of lung cancer was observed in Caucasians (dominant model: OR=1.29, 95%CI=1.11-1.51; recessive model: OR=1.33, 95%CI=1.01-1.75; additive model: OR=1.49, 95%CI=1.12-1.98). There was no evidence of significant association between lung cancer risk and CYP1A2 rs2069514, s2470890, and rs2069526 polymorphisms. Conclusions: In summary, this meta-analysis indicates that the CYP1A2 rs762551 polymorphism is linked to an increased lung cancer risk in Caucasians. Moreover, our work also points out the importance of new studies for rs2069514 associations in lung cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the rs2069514 polymorphism in lung cancer development.

Comprehensive Assessment of Associations between ERCC2 Lys751Gln/Asp312Asn Polymorphisms and Risk of Non-Hodgkin Lymphoma

Zhou, Jue-Yu,He, Li-Wen,Liu, Jie,Yu, Hai-Lang,Wei, Min,Ma, Wen-Li,Shi, Rong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Background: Excision repair crossing-complementing group 2 (ERCC2), also called xeroderma pigmentosum complementary group D (XPD), plays a crucial role in the nucleotide excision repair (NER) pathway. Previous epidemiological studies have reported associations between ERCC2 polymorphisms and non-Hodgkin lymphoma (NHL) risk, but the results have remained controversial. Materials and Methods: We conducted this meta-analysis based on eligible case-control studies to investigate the role of two ERCC2 polymorphisms (Lys751Gln and Asp312Asn) in determining susceptibility to NHL. Ten case-control studies from several electronic databases were included in our study up to August 14, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models to estimate the association strength. Results: The combined results based on all studies did not show any association between Lys751Gln/Asp312Asn polymorphisms and NHL risk for all genetic models. Stratified analyses by histological subtype and ethnicity did not indicate any significant association between Lys751Gln polymorphism and NHL risk. However, a significant reduced risk of NHL was found among population-based studies (Lys/Gln versus Lys/Lys: OR=0.87, 95% CI=0.77-0.99, P=0.037) but not hospital-based studies. As for Asp312Asn polymorphism, there was no evidence for the association between this polymorphism and the risk of NHL in all subgroup analyses. Conclusions: This meta-analysis suggests that there may be no association between Lys751Gln/Asp312Asn polymorphism and the risk of NHL and its two subtypes, whereas ERCC2 Lys751Gln heterozygote genotype may provide protective effects against the risk of NHL in population-based studies. Therefore, large-scale and well-designed studies are needed to clarify the effects of haplotypes, gene-gene, and gene-environment interactions on these polymorphisms and the risk of NHL and its different histological subtypes in an ethnicity specific population.

Roles of E-Cadherin (CDH1) Genetic Variations in Cancer Risk: a Meta-analysis

Deng, Qi-Wen,He, Bang-Shun,Pan, Yu-Qin,Sun, Hui-Ling,Xu, Ye-Qiong,Gao, Tian-Yi,Li, Rui,Song, Guo-Qi,Wang, Shu-Kui Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

E-Cadherin (CDH1) genetic variations may be involved in invasion and metastasis of various cancers by altering gene transcriptional activity of epithelial cells. However, published studies on the association of CDH1 gene polymorphisms and cancer risk remain contradictory, owing to differences in living habits and genetic backgrounds. To derive a more better and comprehensive conclusion, the present meta-analysis was performed including 57 eligible studies of the association between polymorphisms of CDH1 gene promoter -160 C>A, -347 G>GA and 3'-UTR +54 C>T and cancer risk. Results showed that these three polymorphisms of CDH1 were significantly associated with cancer risk. For -160 C>A polymorphism, -160A allele carriers (CA and CA+AA) had an increased risk of cancer compared with the homozygotes (CC), and the similar result was discovered for the -160A allele in the overall analyses. In the subgroup analyses, obvious elevated risk was found with -160A allele carriers (AA, CA, CA+AA and A allele) for prostate cancer, while a decreased colorectal cancer risk was shown with the AA genotype. For the -347 G>GA polymorphism, the GAGA genotype was associated with increased cancer risk in the overall analysis with homozygous and recessive models. In addition, results of subgroup analysis indicated that the elevated risks were observed in colorectal cancer and Asian descendants. For +54 C>T polymorphism, a decreased risk of cancer was found in heterozygous, dominant and allele models. Moreover, +54T allele carriers (CT, CT+TT genotype and T allele) showed a potential protective factor in gastric cancer and Asian descendants.