Association between the CYP1A2 rs762551 Polymorphism and Bladder Cancer Susceptibility: a Meta-Analysis Based on Case-Control Studies

Background: Previous studies evaluated associations between the CYP1A2 rs762551 polymorphism andbladder cancer risk. However, the results were inconsistent. We therefore performed a meta-analysis of thepublished case-control studies to assess in detail the association between CYP1A2 rs762551 polymorphism andbladder cancer risk. Materials and Methods: PubMed, Embase and Web of Science were searched to identifyrelevant studies and the pooled odds ratio (OR) and 95 % confidence interval (95%CI) were calculated. Results:A total of seven articles including 3,013 cases and 2,771 controls were finally included. Overall, a significantassociation was found between the CYP1A2 rs762551 polymorphism and bladder cancer susceptibility for CCvs AA (OR=0.82, 95% CI=0.69~0.99), but no significant associations were found for the other three models (ACvs AA: OR=0.91, 95% CI=0.81~1.02; the dominant model: OR=0.90, 95% CI=0.80~1.00; the recessive model:OR=0.84, 95% CI =0.72~1.00). In the subgroup analysis by ethnicity, we detected significant associationsbetween the CYP1A2 rs762551 polymorphism and bladder cancer susceptibility for GA vs GG (OR = 0.78,95% CI =0.64~0.96) and for the recessive model (OR=0.80, 95% CI=0.66~0.96) in Caucasians, but not forAsians. Conclusions: The results from the meta-analysis suggested that the CYP1A2 rs762551 polymorphism isa protective factor for bladder cancer, especially in Caucasians.     

Association of CYP2E1, STK15 and XRCC1 Polymorphisms with Risk of Breast Cancer in Malaysian Women

Background: Breast cancer is the most common type of cancer affecting Malaysian women. Recent statistics revealed that the cumulative probability of breast cancer and related deaths in Malaysia is higher than in most of the countries of Southeast Asia. Single nucleotide polymorphisms (SNPs) in CYP2E1 (rs6413432 and rs3813867), STK15 (rs2273535 and rs1047972) and XRCC1 (rs1799782 and rs25487) have been associated with breast cancer risk in a meta-analysis but any link in Southeast Asia, including Malaysia, remained to be determined. Hence, we investigated the relationship between these SNPs and breast cancer risk among Malaysian women in the present case-control study. Materials and Methods: Genomic DNA was isolated from peripheral blood of 71 breast cancer patients and 260 healthy controls and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Our study showed that the c1/c2 genotype or subjects with at least one c2 allele in CYP2E1 rs3813867 SNP had significantly increased almost 1.8-fold higher breast cancer risk in Malaysian women overall. In addition, the variant Phe allele in STK15 rs2273535 SNP appeared to protect against breast cancer in Malaysian Chinese. No significance association was found between XRCC1 SNPs and breast cancer risk in the population. Conclusions: This study provides additional knowledge on CYP2E1, STK15 and XRCC1 SNP impact of risk of breast cancer, particularly in the Malaysian population. From our findings, we also recommend Malaysian women to perform breast cancer screening before 50 years of age.     

CYP2D6遗传多态性与肺癌易感性关系的研究

目的探讨CYP2D6Ch基因多态性的频率分布,以及与肺癌的遗传易感性关系.方法应用病例-对照研究及PCR-RFLP等技术,检测肺癌及正常对照各50例的CYP2D6Ch基因型,并应用Logistic回归分析基因多态性与肺癌易感性的关系.结果(1)CYP2D6Ch T/T型(突变型)频率在病例组中为36.0%,在对照组中为50.0%;非T/T型(即C/C合并C/T基因型)与肺癌风险临界升高相关(OR=3.06;95%CI=0.94～9.92).(2)对病例组进行相关变量的分层分析后发现,在肺鳞癌,或轻度吸烟组中,CYP2D6Ch非T/T型与肺癌风险升高显著相关(分别为:OR=3.20,CI=1.04～9.85;OR=7.07,CI=1.16～42.85).结论本文提示CYP2D6Ch基因型分布规律与欧美人群差异较大,且T/T型在肺鳞癌或轻度吸烟者中可作为保护因素而降低肺癌的易感性.     

CYP17 (T- 34C), CYP19 (Trp39Arg), and FGFR2 (C-906T) Polymorphisms and the Risk of Breast Cancer in South Indian Women

Breast cancer is initiated by exposure to endogenous and exogenous estrogens. A case-control (n=250-500)study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP’s) in CYP17 (T-34C),CYP19 (Trp39Arg) and FGFR2(C-906T). Genotyping was done using the Taqman allelic discrimination assayfor CYP17 (T-34C) and FGFR2 (T-906C) and PCR-CTPP for CYP19 (Trp39Arg). There was a significantprotective association of the (TT/CC) genotype of the CYP17 gene against the risk of developing breast cancer(OR=0.68, 95% CI: 0.49-0.96), which was more significant in postmenopausal women (OR=0.56, 95% CI: 0.35-0.89) (p=0.015). CYP19 (Trp39Arg) is a rare polymorphism and all the cases were homozygous for the wild typeTrp allele (100%); this was also the case for 99.2% of the controls. We were unable to detect any variant form ofthe CYP19 gene in south Indian women. There was no significant association between the risk of breast cancerand FGFR2 (C-906T). These results suggest that the CYP17 TT/CC genotype is associated with decreased riskfor breast cancer, especially in post menopausal women.     

Impact of Polymorphism in Base Excision Repair and Nucleotide Excision Repair Genes and Risk of Cervical Cancer: A Case-Control Study

Background: Last few years, several studies all over the world revealed the association of DNA repair genes with risk of developing different type of cancers, but were ambiguous to support the evidences in case of cervical cancer risk. These differences in earlier studies directed us to study the association of polymorphisms of BER genes (XRCC1, hOGG1, XPC) and NER genes (XPC, XPD) with cervical cancer susceptibility in the women of rural population of Maharashtra. Materials and Methods: The genetic polymorphism in BER and NER pathway genes was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using DNA isolated from intravenous blood samples of patients and normal controls. The study included 400 clinically confirmed cervical cancer patients and 400 healthy women from a tertiary care hospital (Krishna Hospital and Medical Research Centre) of south-western Maharashtra. The association of polymorphisms was confirmed by Odds ratio (OR) with 95% confidence interval. Results: The single nucleotide polymorphism (SNP) of BER genes including XRCC1, hOGG1 and APE1 were analyzed and the results were noted that 27466AA (OR=4.88; 95% CI: 3.61- 6.60; p<0.0001) and 28152AA (OR=2.89; 95% CI: 1.57- 5.31; p=0.0005) genotypes of XRCC1 (rs25489, rs25487) were significantly associated with cervical cancer risk. The 1245GG genotype of hOGG1 (rs1052133) (OR=45.30; 95% CI: 3.76- 7.46; p=0.001) also showed significant correlation, whereas 2197GG genotype of APE1 (rs1130409) gene showed negative association with cervical carcinogenesis (OR=0.59; 95% CI: 0.35- 0.97; p=0.005). Similarly when we studied SNPs of NER genes including XPC and XPD genes, 21151TT genotype of XPC (rs 2228000) was positively associated with cervical cancer development and 23591AA genotype of XPD (rs1799793) showed negative association (OR=0.34; 95% CI: 0.17- 0.64; p=0.001). Conclusion: The findings from this study supported that rs25489, rs25487SNPs of XRCC1, rs1052133 of hOGG1 and rs2228000 of XPC may increase cervical cancer risk, whereas rs1130409 SNP of APE1 and rs1799793 SNP of XPD gene lower the risk of cervical cancer in the studied population.     

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

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 metaanalysisof the literature was performed to derive a more precise estimation of the relationship. Materials andMethods: 8 publications covering 23 studies were selected for this meta-analysis, including 1,665 cases and 2,383controls for CYP1A2 rs762551 (from 8 studies), 1,456 cases and 1,792 controls for CYP1A2 rs2069514 (from 7studies), 657 cases and 984 controls for CYP1A2 rs2069526 (from 5 studies) and 691 cases and 968 controls forCYP1A2 rs2470890 (from 3 studies). Results: When all the eligible studies were pooled into the meta-analysisfor the CYP1A2 rs762551 polymorphism, significantly increased lung cancer risk was observed in the dominantmodel (OR=1.21, 95 % CI=1.00-1.46). In the subgroup analysis by ethnicity, significantly increased risk of lungcancer 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 associationbetween lung cancer risk and CYP1A2 rs2069514, s2470890, and rs2069526 polymorphisms. Conclusions: Insummary, this meta-analysis indicates that the CYP1A2 rs762551 polymorphism is linked to an increased lungcancer risk in Caucasians. Moreover, our work also points out the importance of new studies for rs2069514associations 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 cancerdevelopment.     

Associations of CYP2E1 rs2031920 and rs3813867 polymorphisms with colorectal cancer risk: a systemic review and meta-analysis

Cytochrome P450 2E1 (CYP2E1) is a natural enzyme involved in the metabolic activation of many carcinogens, and the functional polymorphisms in the CYP2E1 gene might have impacts on colorectal cancer risk. Many studies were published to assess the associations of CYP2E1 rs2031920 and rs3813867 polymorphisms with colorectal cancer risk, but no consistent findings were reported. A systemic review and meta-analysis of eligible studies was performed to comprehensively assess the associations above. Odds ratios (ORs) with 95 % confidence interval (95 % CIs) were used to assess the strength of the associations. Seventeen studies from 15 publications with 17,082 individuals were finally included into this meta-analysis. Meta-analysis of the 13 studies on CYP2E1 rs2031920 polymorphism showed that there was a significant association between CYP2E1 rs2031920 polymorphism and colorectal cancer risk under two genetic models (c2 versus c1: OR?=?1.19, 95 % CI 1.03–1.37, P?=?0.022; c2c2/c2c1 versus c1c1: OR?=?1.16, 95 % CI 1.00–1.35, P?=?0.046). Meta-analysis of those four case–control studies on CYP2E1 rs3813867 polymorphism showed that there was no significant association between CYP2E1 rs3813867 polymorphism and colorectal cancer risk under all contrast models (c2 versus c1: OR?=?0.96, 95 % CI 0.80–1.16, P?=?0.672; c2c2 versus c1c1: OR?=?1.26, 95 % CI 0.43–3.67, P?=?0.672; c2c2/c1c2 versus c1c1: OR?=?0.95, 95 % CI 0.78–1.16, P?=?0.114; and c2c2 versus c1c2/c1c1: OR?=?1.17, 95 % CI 0.41–3.36, P?=?0.775). Therefore, the findings from this meta-analysis suggest that CYP2E1 rs2031920 polymorphism is associated with colorectal cancer risk, but CYP2E1 rs3813867 polymorphism is not associated with colorectal cancer risk. In addition, more well-designed studies with large sample size are needed to provide a more precise evaluation on the associations above.     

Effects of cytochrome P450 (CYP) 2A6 gene deletion and CYP2E1 genotypes on gastric adenocarcinoma

Cytochrome P450 (CYP) 2A6 and CYP2E1 are enzymes with a high ability to activate a nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), to its potent and ultimate carcinogens. The polymorphic CYP2A6 and CYP2E1 have been implicated in increased susceptibility to certain malignancies. In our study, 120 Japanese patients with gastric adenocarcinoma and 158 healthy controls were compared for frequencies of CYP2A6 and CYP2E1 genotypes. The frequency with which the subjects carried homozygotes of the CYP2A6 gene deletion allele, which causes lack of the enzyme activity, was significantly higher in the gastric cancer patients than in the healthy control subjects (OR = 3.14, 95% confidence interval (95% CI) = 1.05-9.41). Subdividing gastric adenocarcinoma according to tumor differentiation, patients with the well-differentiated type were 4.9-fold more likely to have the CYP2A6 homozygote deletion genotype (OR = 4.91, 95% CI 1.17-20.52). Stratifying by smoking status, we did not find the risk of CYP2A6 gene deletion allele in gastric adenocarcinoma. The CYP2E1 polymorphism detected by RsaI was not significantly different between gastric adenocarcinoma patients (40.8%) and the control population (44.3%). No statistically significant changes were observed when the CYP2E1 genotype was examined relative to tumor differentiation and smoking status. These results suggest that the CTY2A6 deletion is associated with gastric adenocarcinoma among Japanese populations.     

Epoxide hydrolase and CYP2C9 polymorphisms, cigarette smoking, and risk of colorectal carcinoma in the Nurses' Health Study and the Physicians' Health Study

Microsomal epoxide hydrolase (mEH) and cytochrome P450 2C9 (CYP2C9) are involved in the bioactivation and detoxification of polycyclic aromatic hydrocarbons (PAHs) derived from tobacco smoke. Two coding-region mEH variants (Tyr113His, His139Arg) and CYP2C9 variants (Arg144Cys, Ile359Leu) have been described and affect enzyme specific activity. We investigated these polymorphisms and tested interactions with smoking in relationship to risk of colorectal carcinoma in two case-control studies nested in the Nurses' Health Study (NHS) and Physicians' Health Study (PHS) cohorts. mEH Tyr113His and His139Arg polymorphisms were not associated with the risk of cancer among 197 incident cases and 490 controls from the NHS. Among 273 incident cases and 453 controls from the PHS, carrying one or two copies of the 'rapid' 139Arg allele was associated with a significantly reduced risk of colorectal cancer (OR=0.70, 95% CI 0.49--0.99) when compared with His139 wild-type individuals. Risk of colorectal cancer was significantly reduced among men carrying the CYP2C9 *1/*2 genotype (OR=0.62, 95% CI 0.42--0.92) or at least one CYP2C9 variant allele (OR=0.72, 95% CI 0.52--1.00) when compared with *1/*1 wild-type individuals. For women, carrying at least one variant CYP2C9 allele was inversely associated with the risk of colorectal cancer (OR=0.85, 95% CI, 0.57--1.27) when compared with *1/*1 wild-type individuals. No statistically significant genotype-smoking or gene-gene interactions were found in this study. Our results indicate that individuals exposed to tobacco carcinogens were at increased risk of colorectal cancer and that overall risk is related to mEH and CYP2C9 genotype, although the results were not consistent between men and women.     

Genetic Variants of CYP2D6 Gene and Cancer Risk: A HuGE Systematic Review and Meta-analysis

Objective: Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A largenumber of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate withcancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology(HuGE) review and meta-analysis was to summarize the evidence for associations. Methods: Studies focusingon the relationship between CYP2D6 gene polymorphisms and susceptibility to cancer were selected from thePubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data wereextracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6and STATA Version 12.0 software. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated.Results: According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646healthy controls, were included in the meta-analysis. The results showed that there was a positive associationbetween heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, wefound that homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58, 95%CI: 0.34-0.97,P=0.04). Similarly, the G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94,P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively). Conclusion: This meta-analysis suggests that CYP2D6gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840in CYP2D6 gene might increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier (AG+ GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective factors.     

Association of CYP2E1 and NAT2 Polymorphisms with Lung Cancer Susceptibility among Mongolian and Han Populations in the Inner Mongolian Region

Purpose: To explore associations of CYP2E1 and NAT2 polymorphisms with lung cancer susceptibilityamong Mongolian and Han populations in the Inner Mongolian region. Materials and Methods: CYP2E1 andNAT2 polymorphisms were detected by PCR-RFLP in 930 lung cancer patients and 1000 controls. Results: (1)Disequilibrium of the distribution of NAT2 polymorphism was found in lung cancer patients among Han andMongolian populations (p=0.031). (2) Lung cancer risk was higher in individuals with c1, D allele of CYP2E1RsaI/PstI, DraI polymorphisms and slow acetylation of NAT2 (c1 compared with c2, OR=1.382, 95%CI: 1.178-1.587, p=0.003; D compared with C, OR=1.241, 95%CI: 1.053-1.419, P<0.001; slow acetylation compared withrapid acetylation, OR=1.359, 95%CI:1.042-1.768, p=0.056) (3) Compared with c2/c2 and rapid acetylation, c1/c1together with slow acetylation synergetically increased risk of lung cancer 2.83 fold. (4) Smokers with CYP2E1c1/c1, DD, and NAT2 slow acetylation have 2.365, 1.916, 1.841 fold lung cancer risk than others with c2/c2, CCand NAT2 rapid acetylation, respectively. (5) Han smokers with NAT2 slow acetylation have 1.974 fold lungcancer risk than others with rapid acetylation. Conclusions: Disequilibrium distribution of NAT2 polymorphismwas found in lung cancer patients among Han and Mongolian populations. Besides, Han smokers with NAT2slow acetylation may have higher lung cancer risk compared with rapid acetylation couterparts. CYP2E1 c1/c1, DD and NAT2 slow acetylation, especially combined with smoking, contributes to the development of lungcancer. CYP2E1 c1/c1 or DD genotype and NAT2 slow acetylation have strong synergistic action in increasinglung cancer risk.     

CYP2E1PstI/RsaI polymorphism and interaction with tobacco, alcohol and GSTs in gastric cancer susceptibility: A meta-analysis of the literature

Studies investigating the association between cytochrome P450 2E1 (CYP2E1) 5'-flanking region (PstI/RsaI) polymorphism and gastric cancer risk report conflicting results. The rationale for this meta-analysis was to determine whether CYP2E1*2 (c2) variant allele of CYP2E1 increases gastric cancer risk, especially by interacting with smoking, alcohol and other metabolic gene polymorphisms. Two investigators independently searched the Medline and Embase databases. A qualitative scoring of papers was applied to their evaluation. Authors of the identified papers were contacted to obtain data on the mentioned co-exposures. A measurement of the biological interaction among two putative risk factors was estimated by the attributable proportion (AP) due to interaction. We identified 13 case-control studies, which included 2066 gastric cancer cases and 2754 controls. Using the random effects model, we found no association between PstI/RsaI genotype and gastric cancer risk [odds ratio (OR) = 0.97 (95% confidence interval (CI): 0.79-1.18) for c2 allele carriers and OR = 1.36 (95% CI: 0.82-2.25) for c2 homozygotes compared with homozygotes wild-type]. When only high-quality scored studies were considered, a statistically significant increased risk appeared among Asians [OR = 1.50 (95% CI: 1.16-1.94) for c2 carriers and OR = 2.62 (95% CI: 1.23-5.57) for c2 homozygotes]. No interaction was detected between CYP2E1-smoking/alcohol (AP = 0), while an AP of 60% appeared for individuals both c2 homozygotes and glutathione S-transferase M1 (GSTM1) null compared with both homozygotes wild-type. This meta-analysis suggests that the CYP2E1 PstI/RsaI polymorphism may be a risk factor for gastric cancer in Asians, and that a synergic relation among GSTM1 and CYP2E1 may account for a proportion of gastric cancer cases.     

Polymorphisms in CYP1A1 and breast carcinoma risk in a population-based case-control study of Chinese women

BACKGROUND: Cytochrome P450 1A1 (CYP1A1) is involved in the 2-hydroxylation of estrogen, the hormone that plays a critical role in the etiology of breast carcinoma. METHODS: The authors evaluated common polymorphisms in the CYP1A1 gene in relation to breast carcinoma risk in a large population-based case-control study among Chinese women, the Shanghai Breast Cancer Study. Because the CYP1A1*3 and CYP1A1*4 alleles were not detected in the study population, analyses were performed for CYP1A1*2A (T-->C transition in the 3' noncoding region) and CYP1A1*2C (A-->G transition in exon 7, resulting in a substitution of Val for Ile) in 1134 patients with breast carcinoma and 1227 controls. RESULTS: The frequencies of the variant allele were 38.3% and 38.8% among cases and controls (P = 0.91), respectively, for the CYP1A1*2A polymorphism, and 23.1% and 24.8% (P = 0.26) for the CYP1A1*2C polymorphism. Homozygosity for both variant alleles in these 2 polymorphic sites (CYP1A1*2B) was associated with a borderline significant odds ratio (OR) of 0.71 (95% confidence interval [CI], 0.47-1.06). The reduced risk was more pronounced among postmenopausal women with long duration (> 30 yrs) of menstruation (OR = 0.43; 95% CI, 0.19-0.99) or among women with a low waist-to-hip ratio (OR = 0.52; 95% CI, 0.28-0.94). CONCLUSIONS: Results from the current study suggest that homozygosity for the CYP1A1*2A and CYP1A1*2C alleles in the CYP1A1 gene may be associated with a reduced risk for breast carcinoma, particularly among lean women with long-term endogenous estrogen exposure.     

CYP1A1、GSTM1基因多态性及其联合作用与食管癌的易感性

目的探讨CYP1A1、GSTM1基因多态性及其联合作用与新疆汉族人食管癌易感性的关系。方法采用聚合酶链式反应-连接酶检测反应分析方法检测107例食管癌患者和204例非食管癌患者的CYP1A1(rs1048943、rs4646421和rs4646903)和GSTM1(缺失型和rs2071487)的基因型。结果CYP1A1基因rs1048943位点的等位基因和基因型频率在病例组和对照组之间比较,总体分布差异有统计学意义(χ² =5.52,P=0.019)。与A/A基因型相比,GG+AG基因型可增加食管癌的发病风险(OR=1.79,OR95%CI:1.10~2.92);GSTM1基因缺失型和非缺失型在病例组和对照组中的分布频率分别为68.69%、31.31%和48.39%、51.61%,在两组间的分布差异有统计学意义(χ²=10.55,P=0.001;OR=2.34,OR95%CI:1.40~3.91)。结论CYP1A1基因rs1048943位点多态性和GSTM1基因缺失型与新疆地区汉族人食管癌易感性有相关性。     

Polymorphisms of GSTP1 and GSTT1, but not of CYP2A6, CYP2E1 or GSTM1, modify the risk for esophageal cancer in a western population

Esophageal cancer is among the most common and fatal tumors in the world. Eighty percent of esophageal tumors are esophageal squamous cell carcinoma (ESCC). Brazil is one of the high incidence areas in the West, where tobacco and alcohol consumption have been associated with ESCC. However, polymorphisms in xenobiotic metabolizing genes may also contribute to the risk. Therefore, in this study, we analyzed the risk of ESCC associated with tobacco and alcohol consumption and with polymorphisms of CYP2A6 (CYP2A6*2), CYP2E1 (CYP2E1*5B, CYP2E1*6), GSTP1 (Ile105Val), GSTM1 and GSTT1 null genotypes in 126 cases and 252 age- and gender-matched controls. Data on the amount, length and type of tobacco and alcohol consumed were collected, and DNA was extracted from blood lymphocytes from all individuals. Polymorphisms were analyzed by polymerase chain reaction (PCR)-multiplex (GSTM1 and T1), PCR-Restriction Fragment Length Polymorphism (CYP2E1*5B and *6 and GSTP1 Ile105Val) or allele-specific PCR amplification (CYP2A6*2). Risks were evaluated by multivariate conditional regression analysis. As expected, tobacco [odds ratio (OR) = 6.71, 95% confidence interval (95% CI) 3.08-14.63] and alcohol (OR = 16.98, CI 7.8-36.98) consumption, independently or together (OR = 26.91, CI 13.39-54.05) were risk factors. GSTP1 Ile105Val polymorphism was an independent risk factor (OR = 2.12, CI 1.37-3.29), whereas GSTT1 wild-type was an independent protective factor for ESCC (OR = 0.37, CI 0.16-0.79). There was approximately 80% statistical power to detect both results. There was no risk associated with CYP2A6, CYP2E1 and GSTM1 polymorphisms. In conclusion, this study suggests an opposite role of GSTP1 and GSTT1 polymorphisms for the risk for ESCC.     

Meta-analysis of the CYP1A2 -163C>A Polymorphism and Lung Cancer Risk

Many published studies have concerned associations between the CYP1A2 -163 C>A polymorphism and riskof lung cancer, but the results have been inconsistent. Therefore, we performed a meta-analysis to obtain a moreprecise estimate. We searched the PubMed database up to March 1, 2013 for relevant cohort and case-controlstudies. Supplementary search was conducted manually by searching the references of the included studies andrelevant meta-analyses. A meta-analysis was performed using RevMan 5.2 software for calculation of pooledodds ratios (ORs) and relevant 95% confidence intervals (CIs) after data extraction. Finally, seven case-controlstudies and one nested case-control study involving 1,675 lung cancer patients and 2,393 controls were included.The meta-analysis showed that there was no association of CYP1A2 -163 C>A polymorphism with risk of lungcancer overall [(OR=0.89, 95%CI= 0.74-1.07) for C vs. A; (OR=0.73, 95%CI= 0.50-1.07) for AA vs. CC ; (OR=0.82,95%CI= 0.62-1.09) for AC vs. CC; (OR=0.79, 95%CI= 0.58-1.07) for (AC+AA) vs. CC; and (OR=0.87, 95%CI=0.67-1.13) for AA vs. (CC+AC)]. Subgroup analysis indicated that there was an associationbetween CYP1A2-163C>A polymorphism and lung cancer risk for population-based controls, a trend risk for SCCL (squamouscell carcinoma of lung) and Caucasians. These results suggested that -163 C>A polymorphism is likely to beassociated with risk of lung cancer compared with population-based controls.     

Meta-Analysis of Polymorphic Variants Conferring Genetic Risk to Cervical Cancer in Indian Women Supports CYP1A1 as an Important Associated Locus

Objective: Association of multiple polymorphic variants with cervical cancer has been elucidated by severalcandidate gene based as well as genome-wide association studies. However, contradictory outcomes of those studieshave failed to estimate the true effect of the polymorphic variants on cervical cancer. Methods: Literature mining ofthe PubMed database was done to gather all the publications related to genetic association with cervical cancer in India.Out of 98 PubMed hits only 29 genetic association studies were selected for meta-analysis based on specific inclusioncriteria. A fixed-effect meta-analysis was performed to evaluate the overall association of the genetic polymorphismswith cervical cancer. Cochran’s Q test was performed to assess between study heterogeneity. Publication bias wasalso estimated by funnel plots and Egger’s regression test. Further, sub-group analysis was conducted by fixed-effectmeta-regression to assess the impact of polymorphisms on cervical cancer in the presence of Human Papilloma Virus(HPV). Result: Following a fixed-effect model, meta-analysis was conducted that revealed 2 polymorphic variantsviz. ‘deletion polymorphism (Del2) (OR=1.79, 95% CI= 1.08-2.95, P=0.023) in GSTM1’ and ‘rs1048943 (OR = 2.34,95% CI=1.37-3.99, P=0.0018) in CYP1A1’ to be associated with cervical cancer. However, multiple testing correctionshowed only rs1048943 of CYP1A1 to be significantly associated (P-value=0.029) with cervical cancer with significantpublication bias (P-value=0.0113) as estimated by Egger’s regression test. The polymorphic variants ‘rs1801131’,‘rs1801133’, ‘rs2430561’, ‘rs1799782’, ‘rs25486’ and ‘rs25487’ showed significant (p<0.05) evidence of heterogeneitybetween studies by Cochran’s Q test and also by heterogeneity index (I2) calculation. Conclusion: Therefore, our studyrevealed significant association of rs1048943 in CYP1A1, but a nominal association of deletion polymorphism (Del2)in GSTM1 with cervical cancer, which provides a comprehensive insight on the true effect of the polymorphisms,reported in various case-control studies, on the risk of the development of cervical cancer in Indian women.     

Association of IL-12B rs3212227 and IL-6 rs1800795 Polymorphisms with Susceptibility to Cervical Cancer: A Systematic Review and Meta-Analysis

Background: Primary studies have shown that the IL-12B rs3212227 and IL-6 rs1800795 polymorphisms are associated with an increased risk of cervical cancer. However, conflicting results warrant a meta-analysis to obtain more precise estimates. Methods: A comprehensive literate search on PubMed, Web of Science, Scopus, CNKI, and SciELO was performed to collect all eligible studies up to November 10, 2019. The pooled odds ratios (OR) and 95% confidence intervals (CI) were used to calculate the risk. This meta-analysis was carried out by utilizing CMA software. Results: A total of eleven case-control studies including four studies on IL-12B rs3212227 and seven studies on IL-6 rs1800795 were selected. Pooled ORs revealed that the IL-6 rs1800795 polymorphism was significantly associated with an increased risk of cervical cancer (C vs. G: OR = 1.294, 95% CI 1.071-1.564, p= 0.007; CC vs. GG: OR = 1.633, 95% CI 1.059-2.520, p= 0.027; CC+CG vs. GG: OR = 1.312, 95% CI 1.048-1.643, p= 0.018; and CC vs. CG+GG: OR = 1.592, 95% CI 1.268-1.999, p≤0.001), but not IL-12B rs3212227 polymorphism. Stratified analysis by ethnicity revealed that both IL-12B rs3212227 and IL-6 rs1800795 polymorphisms were associated with risk of cervical cancer in Asian women. Conclusions: Our pooled data revealed that the IL-12B rs3212227 and IL-6 rs1800795 polymorphisms may be used to identify individuals at high risk of cervical cancer in Asian women.     

Association of Interactions between Metabolic ‘Caretaker’ Genes,p53, MDM2, and Tobacco Use with the Risk of Oral Cancer: A Multifactor Dimensionality Reduction Approach

Background: The present study investigated the association of interactions between gene polymorphisms in metabolic ‘caretaker’ genes (Phase I: CYP1A1, CYP2E1; Phase II: GSTM1, GSTT1), the cell cycle regulatory gene, p53, along with its negative controller, MDM-2, and the environment variable (tobacco). A nonparametric model, multifactor dimensionality reduction (MDR), was applied to analyse these interactions. Materials and Methods: This case-control study was carried out on 242 subjects. Genomic DNA was extracted from peripheral blood lymphocytes.11 gene variants with an exposure variable (tobacco use) were analysed using MDR to identify the best locus model for gene-gene and gene-environment interactions. Statistical significance was evaluated using a 1000-fold permutation test using MDR permutation testing software (version 1.0 beta 2). The value of p<0.05 was considered statistically significant. Results: The best three-locus model for gene-gene interaction included two of the p53 gene polymorphisms; rs17878362 (intron 3) and rs1042522 (exon 4) and rs6413432 in the Phase I gene, CYP2E1(DraI). The three-locus model to evaluate the gene-environment interaction included two intronic polymorphisms of the p53 gene, that is, rs17878362 (intron 3) and rs1625895 (intron 6), and rs4646903 in the Phase I gene CYP1A1*2C. The interaction graphs revealed independent main effects of the tobacco and p53 polymorphism, rs1042522 (exon 4), and a significant additive interaction effect between rs17878362 (intron 3) and rs1042522 (exon 4). Conclusions: The nonparametric approach highlighted the potential role of tobacco use and variations in the p53 gene as significant contributors to oral cancer risk. The findings of the present study will help implement preventive strategies in both tobacco use and screening using a molecular pathology approach.     

CYP2E1 RsaI/PstI Polymorphism and Liver Cancer Risk among East Asians: a Huge Review and Meta-analysis

Published data on any association between the CYP2E1 RsaI/PstI (c1/c2) polymorphism and liver cancer riskamong east Asians are inconclusive. The aim of this Human Genome Epidemiology (HuGE) review and metaanalysiswas to derive a more precise estimation of the relationship. A literature search of Pubmed, Embase, Webof science and CBM databases from inception through July 2012 was conducted. Twelve case-control studies wereincluded 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 theeligible 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 (c2vs. 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 polymorphismand 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 Koreanpopulations. 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.