四川人群中CYP1A1基因Ile-Val和Msp1位点多态性与肺癌易感性的研究

目的　探讨细胞色素P45 0 (CYP1A1)基因异亮氨酸 (Ile) 缬氨酸 (Val)位点和Msp1位点多态性和肺癌易感性的相关关系。方法　以病例对照的研究方法 ,采用PCR RFLP和ASA PCR技术检测 82例原发性肺癌和 91例对照的CYP1A1基因Ile Val位点和Msp1位点多态性。 结果　Ile Val三种多态基因型在肺癌组和对照组分布差异有显著性 (P <0 .0 5 ) ,Ile/Val、Val/Val基因型在肺癌组的分布频率明显高于对照组 ;logistic回归分析结果显示Ile/Val、Val/Val基因型患肺癌的危险分别是Ile/Ile基因型的 1.969倍和3 .15 0倍 ;当按吸烟分层后 (将Ile/Val、Val/Val基因型合并分析 ) ,吸烟组中Ile/Val、Val/Val合并基因型患肺癌的危险是Ile/Ile基因型的 3 .0 5 9倍 ,而在不吸烟组其OR为 1.687;Msp1位点多态性在肺癌组和对照组差异无统计学意义。结论　CYP1A1第 7外显子的Ile/Val、Val/Val基因型与肺癌的易感性有关 ,可望作为肺癌易感人群筛选的重要指标 ;尚不能认为Msp1多态性与肺癌的易感性有关     

XRCC3 Thr241Met gene polymorphisms and lung cancer risk: a meta-analysis

Many studies have examined the association between the XRCC3 Thr241Met gene polymorphism and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case–control studies published up to July 2012. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.Ultimately, 17 studies, comprising 4123 lung cancer cases and 5597 controls were included. Overall, for T allele carriers (TC + TT) versus the wild-type homozygotes (CC), the pooled OR was 0.95 (95% CI = 0.87-1.04 P = 0.228 for heterogeneity), for TT versus CC the pooled OR was 0.99 (95% CI = 0.86-1.15 P = 0.315 for heterogeneity). In the stratified analysis by ethnicity, histological types of lung cancer and smoking status, no any significantly risks were found for (C/T + T/T) vs C/C or T/T vs C/C. No publication bias was found by using the funnel plot and Egger''s test.Overall, there is no evidence showing a significant correlation between XRCC3 Thr241Met polymorphism and lung cancer risk stratified analysis by ethnicity, histology and smoking status.     

XRCC1 polymorphisms and lung cancer risk in Chinese populations: A meta-analysis

X-ray repair cross-complementing group 1 (XRCC1), one of the >20 genes that participate in the base excision repair (BER) pathway, is thought to account for differences in lung cancer susceptibility. Our meta-analysis on 2861 cases (lung cancer patients) and 2783 controls from eight eligible studies in Chinese populations showed that for the XRCC1 Arg194Trp polymorphism, compared with the Arg/Arg homozygous genotype, the variant Arg/Trp and Trp/Trp genotypes combined was not associated with lung cancer risk (OR = 1.06, 95% confidence interval [CI] = 0.89–1.27) (Z = 0.70, P = 0.48), nor was Arg280His (OR = 0.63, 95% CI = 0.28–1.41) (Z = 1.12, P = 0.26); however, for the XRCC1 Arg399Gln polymorphism, the combination of variant Arg/Gln and Gln/Gln genotypes was borderline significantly associated with lung cancer risk (OR = 1.16, 95% CI = 1.00–1.36) (Z = 1.90, P = 0.06), compared with the Arg/Arg homozygous genotype. Therefore, in the eight published studies in Chinese populations, we found little evidence of an association between the combined variant genotypes of the XRCC1 Arg399Gln polymorphism and the increased risk of lung cancer.     

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.     

Methylenetetrahydrofolate reductase gene C677T polymorphism and lung cancer: an updated meta-analysis

Objective: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotidesneeded for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lungcancer (LC). So far, several studies between MTHFR C677T polymorphism and LC provide controversial orinconclusive results. Methods: To better assess the purported relationship, we performed a meta-analysis of 14publications. Eligible studies were identified by searching the Pubmed, Embase, Web of Science and GoogleScholar 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 LCrisk, the same as in race subgroup. However, in the stratified analysis by histological type, significantly increasednon-small-cell lung cancer (NSCLC) risk was indicated (T-allele vs. C-allele: OR = 1.11, 95%CI = 1.03-1.19; TTvs. 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% decreasedLC risk compared with CC genotype carriers. Conclusions: Our study provided evidence that the MTHFR 677Tnull genotype may increase NSCLC risk, however, it may protect ever-smokers against LC risk. Future studieswith large sample sizes are warranted to further evaluate this association in more detail.     

DNA repair gene polymorphisms in the nucleotide excision repair pathway and lung cancer risk: A meta-analysis

Objective: A number of studies have reported the association of "XPA", "XPC", "XPD/ERCC2" gene polymorphisms with lung cancer risk. However, the results were conflict. To clarify the impact of polymorphisms of "XPA", "XPC", "XPD/ERCC2", on lung cancer risk, a meta-analysis was performed in this study. Methods: The electronic databases PubMed and Embase were retrieved for studies included in this meta-analysis by "XPA", "XPC", "XPD/ERCC2", "lung", "cancer/neoplasm/tumor/carcinoma", "polymorphism" (An upper date limit of October, 31, 2009). A meta-analysis was performed to evaluate the relationship among XPA, XPC and XPD polymorphism and lung cancer risks. Results: A total of 31 publications retrieved from Pubmed and Embase included in this study. XPC A939C CC genotype increased lung cancer risk in total population (recessive genetic model: OR=1.23, 95% CI:1.05-1.44; homozygote comparison: OR=1.21,95%CI:1.02-1.43and CC vs. CA contrast: OR=1.25,95%CI:1.06-1.48), except in Asians. XPD A751C, 751C allele and CC genotype also increased lung cancer risk in total population and in Caucasians (recessive genetic model: Total population: OR=1.20, 95%CI:1.07-1.35). No significant correlation was found between XPD A751C and lung cancer risk in Asians and African Americans. XPD G312A AA genotype increased lung cancer risk in total population, in Asians and Caucasians(recessive genetic model: Total population: OR=1.20, 95%CI: 1.06-1.36). No significant association was found between XPA G23A, XPC C499T, XPD C156A and lung cancer risk. Conclusion: Our results suggest that the polymorphisms in XPC and XPD involve in lung cancer risks. XPA polymorphisms is less related to lung cancer risk.     

SULT1A1 Arg213His polymorphism and lung cancer risk: a meta-analysis

Background: The SULT1A1 Arg213His polymorphism is reported to be associated with lung cancer risk. However, this relationship remains controversial. For better understanding a meta-analysis was therefore performed. Methods: An extensive search was performed to identify all case-control studies investigating association between SULT1A1 Arg213His polymorphism and lung cancer risk. The strength was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95%CI). Results: A total of five publications covering 1,669 cases and 1,890 controls were included in this meta-analysis. No significant association between SULT1A1 Arg213His polymorphism and lung cancer risk was observed in overall comparisons in all genetic models (dominant model: OR=1.33, 95%CI=1.00-1.76, P=0.05; additive model: OR=1.30, 95%CI=0.93-1.81, P=0.12; recessive model: OR=1.21, 95%CI=0.89-1.66, P=0.23). However, on subgroup analysis, an elevated risk in mixed populations with variant His allele was revealed in the dominant model (OR=1.66, 95% CI=1.06-2.62, P=0.03). Furthermore, the SULT1A1 Arg213His polymorphism was associated with an increased risk of lung cancer in both females and males in the dominant model (females: OR=1.72, 95%CI=1.29-2.27, P=0.00; males: OR=1.46, 95%CI=1.19-1.78, P=0.00). No significant association between this polymorphism and different smoking status (smokers and non-smokers) and the other ethnicities (Asians and Caucasians) was shown. Conclusions: The results of this meta-analysis indicate that the SULT1A1 Arg213His polymorphism is not associated with lung cancer risk in Asians and Caucasians, but possible elevation for genotype (GA/AA) in mixed populations and males and females needs further investigation.     

南京市人群NQO1、CYP1A1、mEH基因多态性与肺癌易感性研究

目的：探讨南京市人群人NQO1，CYP1SA1，mEH-exon3,mEH-exon4基因多态性与肺癌易感性的关系。方法：用病例－对照研究方法，收集南京市区原发性肺癌患者84例，其中鳞癌35例，腺癌49例，同时选择对照84例，采用PCR技术，对样本NDA进行NQO1，CYP1A1，mEH-exon3,mEH-exon4基因的检测，并分析各基因型与肺癌易感性的关系。结果：南京市区人群NQO1，CYP1A1和mEH-exon4与肺癌易感性没有明显关系。mEH-exon3基因型与肺鳞癌发生有关，野生型个体可降低肺鳞癌发病的风险（OR＝0．32，95％CI：0．0078－0．63），杂合型和突变型个体患肺鳞癌的危险性明显高于野生型个体（OR＝3．1，95％CI：0．08－6．12），考虑吸烟因素后，mEH-exon3基因型与吸烟者肺癌发生有关，野生型个体可使肺癌发病风险性降低（OR＝0．18，95％CI：0．06－0．29），杂合型和突变型个体患肺癌的危险性增高（OR＝5．66，95％CI：2．01－9．30）。结论：南京市人群中NQO1，CYP1A1，mEH基因的分布情况与国内外的相关报道存在一定差异；种族差异，地域不同可能是造成上述基因分布不同的重要原因，南京市人群中mEH-exon3基因杂合型和变型与肺鳞癌发生有关，与吸烟者肺癌发生关系更为密切。     

CYP1A1和GSTM1基因多态性及其对个体肺癌易感性的联合效应:meta分析

背景与目的谷胱甘肽转移酶M1(glutathione S-transferase M1,GSTM1)和细胞色素P4501A1(cyto-chrome P450A1,CYP1A1)均存在基因多态性,并且对肺癌发病风险有一定的影响,两者联合作用对肺癌发病风险的影响尚无确切定论。本研究旨在探讨CYP1A1和GSTM1基因多态性及其联合效应与肺癌危险性的关系。方法在PubMed数据库、EMBASE数据库、中国生物医学文献数据库(china biology medicine,CBM)和中国知识基础设施工程数据库(china national knowledge infrastructure,CNKI)中查询文献,时间范围从各数据库建库至2011年3月。使用STATA10软件进行meta分析统计,对于每篇入选的文献均计算肺癌发生危险性调整混杂因素后优势比(odd ratio,OR)及其95%置信区间(confidence interval,CI)。结果 15篇文献最终被纳入本次研究。Meta分析显示GSTM1基因缺失时CYP1A1基因IIe/Val位点为纯合突变型时肺癌发病风险明显高于杂合型与纯合突变型联合,总体OR分别...     

NAT2 polymorphism and lung cancer risk: a meta-analysis

N-acetyltransferase 2 (NAT2) gene encodes a key enzyme involved in the metabolism of xenobiotics and whose polymorphisms have been related to individual susceptibility to several malignancies. Although many epidemiological studies have explored the association between NAT2 genetic polymorphism and lung cancer risk, the results remain controversial. In order to assess the overall relationship between NAT2 polymorphism and lung cancer risk, we performed a meta-analysis including 3945 lung cancer cases and 6085 controls from 19 published studies which were selected from 29 articles identified by a search of PubMed up to 1st June 2010. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association. No significant association was found in overall analysis (OR = 1.02, 95% CI = 0.90-1.16, P = 0.01 for heterogeneity) and in subgroup analyses by ethnicity, sex, histological type, smoking status and study design. In conclusion, this meta-analysis found little evidence of an association between the NAT2 polymorphism and the risk of lung cancer.     

MLH1 polymorphisms and cancer risk: a meta-analysis based on 33 case-control studies

Objective: Cumulative evidence suggests that MLH1, the key component in the mismatch pathway, plays an important role in human cancers. Two potential functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in cancer risk. The aim of this meta-analysis was to summarize the evidence for associations. Methods: Eligible studies were identified by searching the electronic literature PubMed, ScienceDirect and Embase databases for relevant reports and bibliographies. Studies were included if of case-control design investigating MLH1 polymorphisms (-93G>A and I219V) and cancer risk with sufficient raw data for analysis. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to evaluate the strength of associations. Results: Our meta-analysis from 33 published case-control studies showed the variant A allele of -93G>A polymorphism to be associated with increased risk in all genetic models (AA vs. GG: OR = 1.22, 95% CI: 1.03-1.44), especially among non-Asians (AA vs. GG: OR = 1.28, 95% CI: 1.04-1.58). For the I219V polymorphism, however, there was no main effect associated with overall cancer risk in any genetic model. Conclusions: The meta-analysis suggested that the MLH1 -93G>A polymorphism may be a biomarker of cancer susceptibility. Large sample association studies and assessment of gene-to-gene as well as gene-to-environment interactions are required to confirm these findings.     

The NQO1 C609T polymorphism and risk of lung cancer: a meta-analysis

Objective: NAD(P)H: quinone oxidoreductase 1 (NQO1) is a cytosolic flavoprotein that catalyzes the two-electron reduction of quinoid compounds into hydroquinones. A single base substitution (CgT) polymorphism at 609 in the NQO1 gene reduces quinone reductase activity. Published data on the association between NQO1 C609T polymorphism and lung cancer risk are conflicting. Methods: To derive a more precise estimation of the relationship, a meta-analysis was performed. Results: A total of 23 studies including 5,575 cases and 9,132 controls were assessed. The pooled result showed that the NQO1 polymorphism was not associated with a clear increased risk of lung cancer (OR = 1.009, 95% CI: 0.943-1.078; P heterogeneity=0.049). In the subgroup analysis by ethnicity, no clear increased risk was found among Asians for TT/CT versus CC (OR = 1.005; 95% CI = 0.890-1.135; Pheterogeneity=0.024). However, the TT and CT genotypes combined were associated with significantly increased risk of lung cancer in Chinese (OR = 1.237, 95% CI: 1.029-1.486; Pheterogeneity=0.061) among whom the variant allele is common. The variant genotype of NQO1 was also associated with modestly increased risk of lung cancer among white populations (OR = 1.017, 95% CI: 0.936-1.105; Pheterogeneity=0.101). However, no significant association was found in Africans with all genetic models. Conclusions: Our meta-analysis suggests that the variant NQO1 C609T genotype may affect individual susceptibility to lung cancer. This meta- analysis suggests that the NQO1 609T allele is a low penetrant risk factor for developing lung cancer in Chinese.     

CYP17 &; SULT1A1 gene polymorphisms in Indian breast cancer

BACKGROUND: Breast cancer is the most common cancer among women worldwide. Life-time exposure to steroid hormones, especially estrogen, is a major risk factor for breast cancer. Functional polymorphisms in genes encoding steroid metabolizing enzymes may thus be important as biomarkers of individual susceptibility to breast cancer. The CYP17 and SULT1A1 genes encode for two enzymes involved in hormone biosynthesis and metabolism. Single nucleotide polymorphisms of these genes may result in inter-individual variability in steroid hormone biosynthesis and metabolism thus influence the development of breast cancer. METHODS: We tested this hypothesis by conducting a case - control study on a group of 140 breast cancer cases and 140 healthy age-matched controls. Analysis of CYP17 and SULT1A1 genotypes were done by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: The genetic polymorphisms of the estrogen-related genes SULT1A1(OR=2.5, 95% CI=1.28-4.98) and CYP17 (OR=4.1, 95= CI=1.78-9.63) were associated with an increased risk of breast cancer among postmenopausal women. Our data also showed evidence for the genetic regulation of serum 17 beta estradiol (E2) levels as measured by ELISA among the premenopausal women with a significant increase in the serum E2 level for the CYP17 A2 variants. CONCLUSION: These results suggest that both CYP17 and SULT1A1 genotypes could be important determinants of breast cancer risk in Indian women and may help in early identification of high risk subjects. Such genotype analysis resulting in a high-risk profile holds considerable promise for individualizing screening, diagnosis and therapeutic intervention in breast cancer.     

Lack of Association Between the CYP1A1 Ile462Val Polymorphism and Endometrial Cancer Risk: a Meta-analysis

Purpose: Any association between the CYP1A1 Ile462Val polymorphism and endometrial cancer risk remainsinconclusive. For a more precise estimate, we performed the present meta-analysis. Methods: PUBMED, OVIDand EMBASE were searched for the studies which met inclusion criteria. Data in all eligible studies wereevaluated and extracted by two authors independently. The meta-analysis estimated pooled odds ratio (OR) with95% confidence interval (CI) for endometrial cancer risk attributable to the CYP1A1 Ile462Val polymorphism.Results: A total of 7 studies were included in this meta-analysis. The results indicated no association betweenendometrial cancer risk and the CYP1A1 Ile462Val polymorphism (for Val vs Ile allele model [OR 1.09, 95%CI 0.73-1.62]; for Val.Val vs Ile.Ile genotype model [OR 1.54, 95% CI 0.56-4.23]; for (Ile.Val + Val.Val) vs Ile.Ilegenotpye model [OR 1.08, 95% CI 0.71-1.63]; for Val.Val vs (Ile.Ile + Ile.Val) genotype model [OR 1.46, 95% CI0.53-4.04]). Conclusions: This meta-analysis suggests that there is no association between endometrial cancerrisk and the CYP1A1 Ile462Val polymorphism.     

Effects of the cyclin D1 polymorphism on lung cancer risk--a meta-analysis

Background: Cyclin D1 (CCND1) is critical in the transition of the cell cycle from G1 to S phases andunbalanced cell cycle regulation is a hallmark of carcinogenesis. A number of studies conducted to assess theassociation between CCND1 G870A polymorphism and susceptibility to lung cancer have yielded inconsistentand inconclusive results. In the present study, the possible association above was assessed by a meta-analysis.Methods: Eligible articles were identified for the period up to November 2011. Pooled odds ratios (OR) with95% confidence intervals (95%CI) were appropriately derived from fixed effects or random-effects models.Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from theHardy-Weinberg equilibrium (HWE) was performed. Results: Ten case-control studies with a total of 10,548subjects were eligible. At the overall analysis the CCND1 870A allele appeared to be associated with elevatedlung cancer risk (for allele model, pooled OR = 1.24, 95% CI: 1.08-1.44, P = 0.004; for homozygous model,pooled OR = 1.45, 95% CI: 1.14-1.84, P = 0.003; for recessive model, pooled OR = 1.29, 95% CI: 1.06-1.58, P= 0.013; for dominant model, pooled OR = 1.33, 95% CI: 1.08-1.65, P = 0.009). Subgroup analyses by ethnicityand sensitivity analysis further pointed to associations, particularly in Asians. Conclusion: This meta-analysissuggests that the A allele of CCND1 G870A polymorphism confers additional lung cancer risk.     

Combined effects of CYP1A1 MspI and GSTM1 genetic polymorphisms on risk of lung cancer: an updated meta-analysis

Genetic polymorphisms of cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genes might contribute to the variability in individual susceptibility to lung cancer, but the reported results from individual studies are not always consistent. We therefore conducted a meta-analysis to systematically estimate the associations between polymorphisms of these two genes and risk of lung cancer. Twenty-one studies with 8,926 subjects were finally enrolled into this study. Meta-analysis was performed by RevMan 5.2. Odds ratio (OR) and its 95 % confidence interval (CI) were calculated to evaluate the susceptibility to lung cancer. Compared with the wild-type homozygous genotype, significantly elevated risk of lung cancer were associated with variant CYP1A1 MspI (m1/m2?+?m2/m2 vs. m1/m1: OR?=?1.27, 95 % CI?=?1.12–1.43, P?P?P?相似文献   

TRAIL-R1 polymorphisms and cancer susceptibility: An evidence-based meta-analysis

Published data on the association between tumour necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1 or DR4) polymorphisms rs20575 (C626G), rs2230229 (A1322G) and rs20576 (A683C) and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of nine studies, among which eight articles including 2941 cases and 3358 controls described C626G genotypes, three articles including 736 cases and 668 controls described A1322G genotypes and three studies totalling 1550 cases and 2257 controls described A683C genotypes were involved in this meta-analysis. Overall, all three polymorphisms were associated with cancer susceptibility. For C626G polymorphism, there was no association between C626G polymorphism and the risk of cancer in all genetic models when all the eligible studies were pooled into the meta-analysis. In the subgroup analysis by source of controls, statistically significantly reduced cancer risks were found among groups with population-based controls for CG versus CC (OR = 0.77, 95% CI:0.65–0.91, P_{heterogeneity} = 0.007) and dominant model (OR = 0.84, 95% CI:0.72–0.99, P_{heterogeneity} = 0.409). For A1322G polymorphism, we found it was associated with a significantly elevated cancer risk of all cancer types in different genetic models (homozygote comparison: OR = 2.80, 95% CI:1.16–6.76, P_{heterogeneity} = 0.905; dominant model comparison: OR = 1.57, 95% CI:1.02–2.41, P_{heterogeneity} = 0.167; and recessive model comparison: OR = 1.22, 95% CI:0.94–1.60, P_{heterogeneity} = 0.535). Similar results were obtained from A683C polymorphism (homozygote comparison: OR = 3.21, 95% CI:1.26–8.20, P_{heterogeneity} = 0.012; dominant model comparison: OR = 1.61, 95% CI: 1.09–2.36, P_{heterogeneity} = 0.000; and recessive model comparison: OR = 2.79, 95% CI: 1.17–6.68, P_{heterogeneity} = 0.025). In summary, this meta-analysis suggests that TRAIL-R1 C626G polymorphism is marginally associated with cancer susceptibility, and both TRAIL-R1 A1322G G allele and A683C C allele are associated with increased risk for cancer.     

Effects of functional genetic polymorphisms in the CYP19A1 gene on prostate cancer risk and survival

CYP19 catalyzes the conversion of androgens to estrogens and is a critical enzyme affecting the sex hormone milieu. In this study, we investigated the functions of CYP19A1 polymorphisms and their associations with prostate cancer risk and clinical outcome. This case‐control study evaluated the effects of three single nucleotide polymorphisms (SNPs) in CYP19A1 on the risk of prostate cancer in 330 prostate cancer patients and 354 normal controls. The associations between each SNP and sex hormone levels were evaluated in 164 healthy male patients. The functions of the SNPs were determined by reporter gene assays in PC3 and DU145 cell lines. Prostate‐specific antigen nadir was evaluated in 142 patients with metastatic prostate cancer treated with androgen deprivation therapy. Cancer‐specific survival (CSS) was determined in 166 patients with metastatic prostate cancer, to evaluate the influence of the three SNPs. Each variant allele of the three SNPs significantly decreased the risk of prostate cancer. Haplotype analysis showed that the T‐A‐G haplotype (corresponding to rs2470152‐rs10459592‐rs4775936) increased the risk of prostate cancer, while the C‐C‐A haplotype decreased the risk. The estrone/androstenedione ratio was significantly higher in men with the C allele of rs2470152, the C allele of rs10459592, and the A allele of rs4775936 in a gene‐dosage‐dependent manner. Patients with the variant allele at rs4775936 had significantly shorter CSS. These results indicate that CYP19A1 polymorphisms may influence prostate cancer risk and survival by modifying promoter activity, with subsequent effects on the sex hormone milieu.     

CYP2A6基因多态性与肺癌易感性关系的研究

背景与目的代谢活化酶细胞色素P4502A6(CYP2A6)在尼古丁氧化及其他烟草致癌物的活化过程中发挥重要的作用。研究认为携带CYP2A6缺失型等位基因的个体患肺癌的危险性降低。本研究旨在探讨CYP2A6与肺癌易感性的关系,为确定肺癌易感性遗传标记提供依据。方法采用病例-对照研究方法及巢式PCR技术检测原发性肺癌组(180例)及对照组(224例)的CYP2A6代谢酶基因型。结果对照组只检测出1例纯合型CYP2A6缺失,CYP2A6杂合缺失型所占比例为13.4%。在肺癌组中CYP2A6杂合缺失型所占比例为12.8%,未能检测出纯合型CYP2A6缺失。两组间比较没有统计学差异(P>0.05)。结论CYP2A6突变基因在肺癌组及对照组中的频率分布没有差异。     

Concurrent expression of aryl hydrocarbon receptor and CYP1A1 but not CYP1A1 MspI polymorphism is correlated with gastric cancers raised in Dalian, China

The frequency of cancer-associated m2m2- (C-) genotype of CYP1A1 and the factors contributing to the increased CYP1A1 expression in gastric cancers (GCs) are largely unknown. To address theses issues, PCR-restriction fragment length polymorphism (PCR-RFLP) was performed to elucidate the MspI polymorphism in 60 GC cases and 57 normal donor samples. The frequencies of m1m1-, m1m2- and m2m2-genotype were 43.3, 45 and 11.7% among GC patients and 45.6, 49.1 and 5.3% among the normal donors respectively, demonstrating no significant difference of them between cancer and control groups (χ²=0.343, P=0.558). The correlation of Aryl hydrocarbon receptor (AhR) with the frequent CYP1A1 expression in stepwise gastrocarcinogenesis was determined by RT-PCR, immunohistochemical staining (IHC) and Western blotting, using GC samples as well as their pre-malignant and non-cancerous counterparts. RT-PCR revealed that the AhR detection rates were 100, 94.12 and 85.17% in GC, pre-malignant and non-cancerous mucosa (P>0.05) respectively but the level of AhR expression in GCs was much higher than that of non-cancerous tissues. IHC showed that the frequencies of AhR detection were 94.87% (37/39) in GCs, 94.12% (16/17) in pre-malignant lesions and 50% (3/6) in non-cancerous mucosa, revealing significant difference in frequencies of AhR detection and levels of AhR expression between GC or pre-malignant group and non-cancerous one (P<0.05). The frequency of AhR nucleus translocation was significantly high in GCs (94.87%; 37/39) than that in pre-malignant (70.59%; 12/17) and especially in non-cancerous group (16.67%; 1/6). Co-existence of AhR nuclear translocation and CYP1A1 expressions were found in 82.70% (43/52) of GCs (r_s=0.437, P<0.01). Our results suggest (1) that CYP1A1 MspI polymorphism may not contribute to the high gastric cancer risk in Dalian region and (2) that enhanced AhR expression and especially its nuclear translocation may be a favorable factor for GC formation presumably via up-regulating CYP1A1 expression.