The Cyclin D1 G870A Polymorphism and Colorectal Cancer Susceptibility: A Meta-analysis of 20 Populations

Purpose: Studies of the association between the cyclin D1 (CCND1) G870A genetic polymorphism and riskof colorectal cancer (CRC) have generated conflicting results. In order to derive a more precise estimation, ameta-analysis was here performed. Materials and methods: An extensive search of relevant studies was carriedout as a meta-analysis of twenty studies with 5,975 cases and 8,333 controls. Results: Overall, a significantlyelevated colorectal cancer risk was associated with variant allele 870A when all studies were pooled (AA vs.GG: OR = 1.23, 95%CI = 1.04-1.44; GA vs. GG: OR = 1.13, 95%CI = 1.01-1.26; dominant model: OR = 1.16,95%CI = 1.03-1.31). In the subgroup analysis by ethnicity, significantly increased risks were detected amongCaucasians (AA vs. GG: OR = 1.27, 95%CI = 1.04-1.44; and dominant model: OR = 1.17, 95%CI = 1.02-1.34).With stratification into sporadic CRC and hereditary nonpolyposis colorectal cancer (HNPCC), the formerdemonstrated increased cancer susceptibility (AA vs. GG: OR = 1.24, 95%CI = 1.04-1.48; dominant model:OR = 1.17, 95%CI = 1.04-1.33). However, no significant associations were found in either Asians or HNPCCpatients for any genetic model. Conclusion: The results suggest that the cyclin D1 870A allele is a low-penetrantrisk factor for development of sporadic colorectal cancer, especially among Caucasians.     

Cyclin D1 (CCND1) G870A polymorphisms and cervical cancer susceptibility: a Meta-analysis based on Ten case–control studies

Many studies have evaluated the association between cyclin D1 (CCND1) G870A polymorphism and cervical cancer susceptibility. However, these studies showed inconsistent results. The aim of this study was to derive a more precise estimation of this association. We searched PubMed and Embase for related studies that had been published in English, and ten case–control studies with a total of 2,864 cases and 3,898 controls were finally identified to be eligible studies in the meta-analysis. The association was assessed by summarizing the odds ratios (ORs) with the corresponding 95 % confidence intervals (CIs). Overall, there was no significant association between cyclin D1 (CCND1) G870A polymorphism and cervical cancer risk (for the allele model A vs. G: OR?=?1.02, 95 % CI 0.88–1.19, p?=?0.76; for the co-dominant model AA vs. GG: OR?=?1.03, 95 % CI 0.75–1.41, p?=?0.85; for the dominant model AA?+?GA vs. GG: OR?=?1.00, 95 % CI 0.78–1.28, p?=?0.99; for the recessive comparison AA vs. GA?+?GG: OR?=?1.06, 95 % CI 0.85–1.32, p?=?0.62). In subgroup analysis by ethnicity, no significant difference was found in both Asians and Caucasians. In summary, the present meta-analysis provides evidence that genotypes for the cyclin D1 (CCND1) G870A polymorphism may be not associated with genetic susceptibility of cervical cancer.     

Association Between the hsa-mir-27a Variant and Breast Cancer Risk: a Meta-analysis

Introduction: Although a number of studies were published in the past several years on associations betweenhsa-mir-27a and cancer risk, the findings remain conflicting rather than conclusive. To derive a more precise effecton the association between SNP hsa-mir-27a rs895819 and breast cancer risk, we conducted a meta-analysis forthe first time. Materials and Methods: Through retrieval from PubMed for the period up to August 2012, a totalof four studies were identified with 3,287 cases and 4,298 controls for SNP hsa-mir-27a rs895819.We calculatedsummary odds ratio (ORs) and corresponding 95% confidence intervals (CIs) using a fixed effects model (whenthe heterogeneity was absent, P>0.10). Otherwise, the random-effects model was used. Results: We found thathsa-mir-27a rs895819 polymorphism also did not reveal any relationship with breast cancer susceptibility (AGversus AA: OR = 0.98; 95%CI, 0.73-1.32; GG versus AA: OR = 0.86; 95% CI, 0.72-1.03; AG/GG versus AA:OR = 0.92; 95% CI, 0.74-1.14), while significantly decreased risk was found among Europeans in AG versus AAand AG/GG versus AA models tested (AG versus AA: OR = 0.83; 95%CI, 0.72-0.97; GG versus AA: OR = 0.86;95% CI, 0.71-1.05; AG/GG versus AA: OR = 0.84; 95% CI, 0.75-0.94). Conclusion: These findings suggest thathsa-mir-27a rs895819 polymorphism may play an important role in breast cancer development.     

白介素10-1082G/A位点单核苷酸多态性与中国北方人群胃癌发病风险的病例对照研究

背景与目的:个体遗传易感性对胃癌的发生发展具有重要作用,其中免疫抑制因子白细胞介素10(interleukin-10,IL-10)基因-1082G/A位点单核苷酸多态性(single anucleotide polymorphism,SNP)引起研究者重视。本研究分析IL-10-1082G/A SNP在中国北方胃癌高发区和低发区人群中的分布,探讨IL-10-1082G/A SNP与胃癌发病风险的关系。方法:1516例研究对象来自胃癌高发区辽宁庄河(983例)及低发区沈阳(533例),采用聚合酶链反应-限制性片段长度多态(polymerase chain reaction-restriction fragment lengthpolymorphism,PCR-RFLP)方法检测该人群中IL-10-1082G/A位点单核苷酸多态性;采用酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)检测血清幽门螺杆菌(Helicobacter pylori,H.pylori)IgG。采用病理组织学诊断进行疾病分组,按性别和年龄配对,选取基本正常、浅表性胃炎、胃糜烂溃疡、萎缩性胃炎和胃癌组织各111例,用于IL-10-1082G/A SNP与胃癌发病风险的分析。结果:中国北方人群IL-10-1082G/A基因位点AA、AG、GG三种基因型分布频率分别为88.5%、10.9%、0.6%。IL-10-1082AG GG基因型在胃癌组、非胃癌组及正常对照组分布频率分别为19.8%、9.7%和6.3%,IL-10-1082AG GG基因型在胃癌高、低发区人群中的分布的地区及性别差异无统计学意义(P>0.05),而胃癌组高于非胃癌组(P=0.003)及正常对照组(P=0.003),其差异均有统计学意义。以IL-10-1082AA基因型并H.pylori IgG阴性的正常组为对照,IL-10-1082AG GG基因型并H.pylori IgG抗体阴性个体、IL-10-1082AA基因型或AG GG基因型并H.pylori IgG抗体阳性个体胃癌患病风险均提高,OR(95%CI)分别为3.3(1.3～8.6)、4.3(2.0～9.5)、2.5(2.1～3.1),但三组两两进行比较其差异均无统计学意义(P>0.05)。结论:携带IL-10-1082AG GG基因型个体胃癌的发病风险提高,IL-10-1082G/A SNP和H.pylori感染在胃癌发生发展过程中无交互作用。     

A Cyclin D1 (CCND1) Gene Polymorphism Contributes to Susceptibility to Papillary Thyroid Cancer in the Turkish Population

Cyclin D1 is an important positive regulator of the G1/S phase of the cell cycle. We investigated the association between the CCND1 G870A polymorphism and susceptibility to papillary thyroid cancer in Turkish people. This study covered 102 patients with papillary thyroid cancer and 174 healthy controls. CCND1 genotypingwas determined by the PCR-RFLP method. We found that the A allele frequency was higher in the cases than in the controls (p=0.042). On stratification analysis, papillary thyroid cancer risk was significantly elevated in individuals older than 45 years with the A allele (OR=1.91, 95% CI, 1.09-3.35, p=0.024) and in females with the A allele (OR=1.73, 95% CI, 1.06-2.84, p=0.029), compared to the G allele. According to the subject age, there was an increased papillary thyroid cancer risk for the individuals older than 45 years with the AA genotype (OR=2.28, 95% CI, 1.02-5.13, p=0.046) compared to the AG+GG combined genotypes. In conclusion, it is suggested that the CCND1 G870A polymorphism may contribute to the susceptibility to papillary thyroid cancer, especially in those who were older subjects (45≤ years old) and female, in the Turkish population.     

PLCε1基因多态性与食管癌遗传易感性的关联研究

  目的  探讨PLCε1基因rs2274223 A/G单核苷酸多态性(single nucleotide polymorphism,SNP)和rs11599672 T/G SNP与河北省磁县高发区人群食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)遗传易感性之间的关系。  方法  采用聚合酶链反应-连接酶检测反应(polymerase chain reaction-ligase detection reaction,PCR-LDR)方法对527例ESCC患者和527例健康对照PLCε1基因rs2274223 A/G SNP和rs11599672 T/G SNP进行基因分型。  结果  ESCC患者组上消化道肿瘤(upper gastrointestinal cancer,UGIC)家族史阳性个体比例为48.6%,显著高于健康对照组(39.3%,χ2=9.25,P=0.002)。ESCC患者组及健康对照组PLCε1基因rs2274223 A/G SNP AA、AG、GG基因型频率分别为48.0%、43.9%、8.1%和57.1%、37.5%、5.4%。与AA基因型相比,携带AG、GG、AG/GG基因型可能增加ESCC的发病风险,经年龄、性别、吸烟状况、UGIC家族史校正后的OR值分别为1.41(95%CI=1.09~ 1.83)、1.71(95%CI=1.03~2.86)、1.45(95%CI=1.13~1.85)。PLCε1基因rs11599672 T/G SNP等位基因频率和基因型频率总体分布在ESCC患者组及健康对照组之间无显著性差异(P>0.05)。应用2LD软件对PLCε1基因rs2274223 A/G SNP和rs11599672 T/G SNP进行联合分析显示,两个多态性位点间不存在连锁不平衡现象(D'=0.11)。与最常见的AT单体型相比,GT单体型增加了ESCC的发病风险(OR=1.36,95%CI=1.08~1.71)。  结论  PLCε1基因rs2274223 A/G SNP可以作为高发区人群ESCC遗传易感性的标志物。UGIC家族史阳性个体、携带PLCε1基因rs2274223 A/G SNP AG、GG基因型的个体罹患ESCC的风险较高,应定期接受食管内镜检查,以便真正实现ESCC的早期诊断、早期治疗。      

Association Between Single Nucleotide Polymorphisms in the XRCC1 Gene and Susceptibility to Prostate Cancer in Chinese Men

Background: Prostate cancer (Pca) is one of the most common complex and polygenic diseases in men. TheX-ray repair complementing group 1 gene (XRCC1) is an important candidate in the pathogenesis of Pca. Thepurpose of this study was to evaluate the association between single nucleotide polymorphisms in the XRCC1gene and susceptibility to Pca. Materials and Methods: XRCC1 gene polymorphisms and associations withsusceptibility to Pca were investigated in 193 prostate patients and 188 cancer-free Chinese men. Results: Thec.910A>G variant in the exon9 of XRCC1 gene could be detected by polymerase chain reaction-restriction fragmentlength polymorphism (PCR-RFLP) and DNA sequencing methods. Significantly increased susceptibility toprostate cancer was noted in the homozygote comparison (GG versus AA: OR=2.95, 95% CI 1.46-5.42, χ2=12.36,P=0.001), heterozygote comparison (AG versus AA: OR=1.76, 95% CI 1.12-2.51, χ2=4.04, P=0.045), dominantmodel (GG/AG versus AA: OR=1.93, 95% CI 1.19-2.97, χ2=9.12, P=0.003), recessive model (GG versus AG+AA:OR=2.17, 95% CI 1.33-4.06, χ2=8.86, P=0.003) and with allele contrast (G versus A: OR=1.89, 95% CI 1.56-2.42,χ2=14.67, P<0.000). Conclusions: These findings suggest that the c.910A>G polymorphism of the XRCC1 geneis associated with susceptibility to Pca in Chinese men, the G-allele conferring higher risk.     

Associations of functional polymorphisms in cyclooxygenase-2 and platelet 12-lipoxygenase with risk of occurrence and advanced disease status of colorectal cancer

Aberrant arachidonic acid metabolism by cyclooxygenase (COX)-2 and 12-lipoxygenase (LOX) has implicated in carcinogenesis. Genetic polymorphisms in COX-2 and 12-LOX might therefore affect susceptibility to colorectal cancer (CRC). To examine this hypothesis, genotypes of COX-2 -1290A>G, -1195G>A, -765G>C and 12-LOX 261Arg>Gln polymorphisms were determined in 1000 CRC patients and 1300 controls. Increased risk of developing CRC was associated with the COX-2 -1195GA [adjusted odds ratio (OR) = 1.24, 95% confidence interval (CI) = 1.00-1.54] and -1195AA (adjusted OR = 1.77, 95% CI = 1.38-2.25) genotypes compared with the -1195GG genotype. Similarly, the increased risk for CRC was also associated with the COX-2 -765GC genotype (adjusted OR = 1.73, 95% CI = 1.23-2.43) compared with the -765GG genotype. Consistent with the results of genotype analyses, the ORs for the A_(1195)-C_(765)-containing haplotypes were significantly higher than those for the G_(1195)-G_(765)-containing haplotypes (P < 0.01). Furthermore, the -1195A allele was further associated with advanced CRC, with adjusted ORs of Dukes D CRC against Dukes A CRC being 2.43 (95% CI = 1.15-4.97) and 2.66 (95% CI = 1.23-5.74) for the -1195GA and -1195AA genotypes, respectively. The increased risk of CRC was also associated with the 12-LOX 261Gln/Gln genotype compared with the Arg/Arg genotype (adjusted OR = 1.38, 95% CI = 1.09-1.74). Together, these observations indicate that inherited polymorphisms in arachidonic acid-metabolizing enzymes may confer susceptibility to CRC.     

Cyclin D1 G870A polymorphism and breast cancer risk: a meta-analysis involving 23,998 subjects

Cyclin D1 (CCND1) plays an essential role in tumor development and progression through regulating the cell transition from G1 to the proliferative S phase. The CCND1 G870A polymorphism has been associated with an increased susceptibility to squamous cell carcinoma of the head and neck, bladder, prostate, and gastric cardiac cancers. There are a number of studies that explored the relationship between CCND1 G870A polymorphism and breast cancer risk, with inconsistent conclusions. In order to better define the predictive value of CCND1 G870A polymorphism in breast cancer, we searched PubMed and EBSCO for relevant publications. A total of 13 studies were indentified, which included 11,235 cases and 12,763 controls. We calculated the summary odds ratios and the corresponding 95% confidence interval. Our meta-analysis showed that carriers of AA genotype have a significantly higher risk in developing breast cancer compared with that of GG genotype (OR = 1.08, 95% CI = 1.01-1.17, p > = 0.03) in overall population. Furthermore, in subgroup analysis, CCND1 G870A polymorphism was associated with a marginally increased risk of breast cancer for Chinese compared to Caucasian populations with an OR = 1.14, 95% CI = 1.00-1.20, p-trend = 0.06 for AA + GA versus GG, if the controls were hospital-based population with an OR = 1.21, 95% CI = 0.99-1.47, p = 0.06 for AA versus GG and if the distributions of genotypes in control groups were consistent with the Hardy-Weinberg equilibrium (HWE) with an OR = 1.08, 95% CI = 1.00-1.15, p = 0.04 for AA versus GA + GG. Our meta-analysis represents the largest study to date indicating that the G870A polymorphism in CCND1 confers an increased risk for breast cancer. Further studies are warranted to explore the preventive measures to detect and manage the breast cancers attributable to the G870A polymorphism.     

Cyclin D1 gene polymorphism as a risk factor for oral premalignant lesions

BACKGROUND: Deregulation of cell cycle plays an important role in tumorigenesis. Cyclin D1 gene (CCND1) is a key regulator of the G(1) phase of the cell cycle. METHODS: In this case-control study of 115 oral premalignant lesion (OPL) patients and 230 controls, we genotyped the CCND1 single nucleotide polymorphism (SNP) at the exon 4 splice site (G870A) and determined the association of this SNP with the risk of developing OPLs. RESULTS: We found significant associations between the heterozygous variant allele (GA), the homozygous variant allele (AA) and OPL risk, with adjusted odds ratios (ORs) of 1.91 [95% confidence interval (CI), 1.05-3.48] and 2.38 (95% CI, 1.16-4.87), respectively. The OR for individuals with at least one variant allele was 2.04 (95% CI, 1.15-3.60). When further stratified analyses were performed, the increased risk was more evident in younger individuals (OR = 2.82; 95% CI, 1.32-6.02), in men (OR = 2.97; 95%CI, 1.31-6.71) and in never smokers (OR = 2.92; 95% CI, 1.09-7.82). Finally, we found joint effects between the variant alleles and the smoking status. Using never smokers with the wild-type (GG) genotypes as the reference group, the ORs for never smokers with the variant genotypes (G/A + A/A), smokers with the G/G genotype and smokers with the G/A + A/A genotypes were 2.92 (1.09-7.82), 3.95 (1.36-11.5) and 7.01 (2.68-18.4), respectively. CONCLUSION: Our results suggest that the CCND1 G870A SNP may contribute to genetic susceptibility to OPLs and involve in oral cancer development.     

Polymorphisms of FAS and FAS ligand genes involved in the death pathway and risk and progression of squamous cell carcinoma of the head and neck.

PURPOSE: Alteration of the FAS/FAS ligand (FASLG) pathway regulating cell death may lead to cancer development, but the effects of functional promoter polymorphisms of the FAS and FASLG genes on risk of squamous cell carcinoma of the head and neck (SCCHN) are unknown. DESIGN: We genotyped the FAS -1377 G>A, FAS -670 A>G, FASLG -844 C>T, and FASLG IVS2nt -124 A>G polymorphisms in 721 case patients with SCCHN and 1,234 cancer-free non-Hispanic White control subjects frequency-matched by age and sex. Multivariate logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Compared with the FAS -1377 GG and -670 AA genotypes, the FAS -1377 AA and -670 (GG+AG) genotypes were associated with an increased risk of SCCHN (OR, 2.23; 95% CI, 1.07-4.64 and OR, 1.24; 95% CI, 1.01-1.52, respectively), whereas no risk of SCCHN was associated with any of the FASLG genotypes. When we used the combined FAS -1377 (GG+AG)/-670 AA genotypes as the reference, we found that the individuals carrying the FAS -1377 AA/-670 (GG+AG) had the highest risk (OR, 2.69; 95% CI, 1.24-5.83), whereas individuals carrying genotypes other than FAS -1377 (GG+AG)/-670 AA had a higher risk of SCCHN (OR, 1.24; 95% CI, 1.01-1.52). Furthermore, the elevated risk was particularly evident for pharyngeal cancer with the larger tumors without regional lymph metastasis (OR, 1.77; 95% CI, 1.07-2.94). CONCLUSIONS: The FAS (but not FASLG) polymorphisms seem to contribute to risk of developing SCCHN, particularly the pharyngeal cancer in non-Hispanic Whites. However, potential selection bias warrants future population-based studies to verify the findings.     

The association of cyclin D1 G870A and E-cadherin C-160A polymorphisms with the risk of colorectal cancer in a case control study and meta-analysis

Cyclin D1 (CCND1) and E-cadherin (CDH1) have been shown to be important genes of the beta-catenin/LEF pathway that is involved in colorectal carcinogenesis. However, epidemiological studies on relationship between genetic variants of these two genes and colorectal cancer (CRC) have shown inconsistent results. In a population-based case-control study (498 cases and 600 controls), we assessed the association of CCND1 G870A and CDH1 C-160A polymorphisms with CRC risk. Multivariable logistic regression analysis was used to estimate the association between genotypes, environmental exposures and CRC risk, adjusting for potential confounders. Compared to common homozygotes, the OR for heterozygous and homozygote variant genotype was 1.08 (95% CI, 0.80-1.46) in CCND1 and 0.97 (95% CI, 0.75-1.25) in CDH1. Neither tumor stage nor location showed an association with genetic susceptibility. However, a significant interaction between hormone replacement therapy (HRT) and CCND1 genotypes in CRC risk was found among postmenopausal women (p(interaction) = 0.02). The risk reduction associated with HRT was substantial (OR, 0.09; 95% CI, 0.02-0.35) in women who were GG homozygous. A meta-analyses including 11 published studies on CCND1 G870A in addition to our study showed a slightly increased risk of CRC for carriers of the A allele (OR, 1.19; 95% CI, 1.06-1.34); however, there was some indication of publication bias. We conclude that the CCND1 G870A and CDH1 C-160A polymorphisms are not associated with the risk of CRC in the German population. However, the CCND1 G870A polymorphism may modify the protective effect of postmenopausal hormone use on the development of CRC.     

Cyclin D1 polymorphism and risk for squamous cell carcinoma of the head and neck: a case-control study

A G-->A polymorphism (G870A) in exon 4 of the cyclin D1 (CCND1) gene creates an alternative splice site in its mRNA, encoding a protein with an altered C-terminal domain. It has been suggested that DNA damage in cells with the A allele bypasses the G(1)/S checkpoint of the cell cycle more easily than damage in cells without the A allele. Because CCND1 plays a critical role in cell cycle control and reduced DNA repair capacity is associated with an increased risk for squamous cell carcinoma of the head and neck (SCCHN), we hypothesize that this CCND1 polymorphism modulates individual susceptibility to SCCHN. To test this hypothesis we evaluated the frequency of the polymorphism in a hospital-based case-control study of 233 newly diagnosed SCCHN patients and 248 non-cancer controls. The cases and controls were frequency matched by age (+/-5 years), sex and tobacco use. All subjects were non-Hispanic whites. We found that the A allele frequency was slightly higher in the cases (0.485) than in the controls (0.425), but the difference was borderline statistically significant (P = 0.064). The frequencies of the CCND1 AA, GA and GG genotypes were 23.6, 49.8 and 26.6%, respectively, in cases and 16.5, 52.5 and 31.5%, respectively, in controls. Multivariate logistic regression analysis adjusting for age (in years), sex, smoking and alcohol use was performed to calculate odds ratios (OR) and 95% confidence intervals (CI). Compared with the wild-type CCND1 GG, the CCND1 A G genotype was associated with a non-significantly increased risk (adjusted OR 1.15, 95% CI 0.75-1.76), but the CCND1 AA genotype was associated with a significantly increased risk (adjusted OR 1.77, 95% CI 1.04-3.02) for SCCHN. Results from a trend test using a logistic regression model were statistically significant (P = 0.044). Among the cases the mean age of onset was 59.0, 56.8 and 55.5 years for the GG, GA and AA genotypes, respectively. In the stratification analysis the CCND1 AA variant genotype was associated with a >3-fold increased risk in individuals who were 相似文献   

Association of cyclin D1 polymorphism with increased susceptibility to oral squamous cell carcinoma

We have examined the association of the CCND1 A/G870 polymorphism with susceptibility and outcome in 174 German patients with oral SCC (OSCC). The CCND1 G870 allele frequency was increased in cases (G870=0.65) when compared to controls (n=155, G870=0.54) and the distribution of CCND1 genotypes were significantly different (p=0.014). Using logistic regression, correcting for age, gender and tobacco consumption, an increased frequency of the CCND1 GG870 genotype was observed in the OSCC cases (p=0.025, OR 3.37, 95% CI 1.61-9.80). No significant associations were observed between CCND1 A/G870 and tumour histological factors. Our data suggests that the CCND1 GG870 genotype is associated with increased susceptibility to OSCC. The involvement of cyclin D1 polymorphism in mechanisms of SCC development may differ in the different sub-sites of the head and neck.     

Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non-Hodgkin's lymphoma in adults.

Folate and methionine metabolism is involved in DNA synthesis and methylation processes. Polymorphisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In a case-control study, we evaluated whether four common polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G), and methionine synthase reductase (MTRR A66G) genes may have a role in altering susceptibility to adult acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). We analyzed DNA of 120 adult ALL, 200 NHL, and 257 healthy control subjects. Individual carrying the MTHFR 677TT genotype showed a 3.6-fold decreased ALL risk [odds ratio (OR) 0.28, 95% confidence interval (95% CI) 0.12-0.72] than wild-types. Similarly, MS 2756GG individuals showed a 5.0-fold decreased ALL risk (OR 0.20, 95% CI 0.02-1.45) than wild-types. In combined results, subjects with the MTHFR 677CT/TT and MS 2756AG/GG genotypes revealed a 3.6-fold ALL risk reduction (OR 0.28, 95% CI 0.14-0.58) and those with the MTHFR 677TT and MTRR 66AG genotypes revealed a 4.2-fold ALL risk reduction (OR 0.24, 95% CI 0.06-0.81). Finally, those with the MS 2756AG/GG and MTRR 66AG/GG genotypes revealed a 2.2-fold ALL risk reduction (OR 0.45, 95% CI 0.10-0.85). Single analysis for NHL did not show any significant difference for all the polymorphisms investigated, but in the low-grade NHL subgroup, we found a 2.0-fold risk reduction for the MTRR 66GG homozygous genotype (OR 0.50, 95% CI 0.25-0.99), which was higher (OR 0.37, 95% CI 0.14-0.85) when analyzed in combination with MS 2756AA genotype. These data are in accordance with the hypothesis that polymorphisms in the genes for folate and methionine metabolism might play a greater role in the occurrence of ALL than NHL by influencing DNA synthesis and/or DNA methylation.     

Association of cyclin D1 (G870A) polymorphism with susceptibility to esophageal and gastric cardiac carcinoma in a northern Chinese population

Our aim was to investigate the association of cyclin D1 (G870A) single nucleotide polymorphism with susceptibility to esophageal and cardiac carcinoma in a northern Chinese population. By polymerase chain reaction-single strand conformation polymorphism analysis, cyclin D1 (G870A) genotyping was carried out among 120 patients with esophageal squamous cell carcinoma (ESCC), 87 patients with gastric cardiac adenocarcinoma (CAC), and 183 age- and gender-matched controls. The cyclin D1 genotype distribution among ESCC patients was significantly different from that among healthy controls (chi(2) = 7.372, p = 0.025). The G/G genotype was significantly less frequent among ESCC patients (9.2%) than among healthy controls (20.8%) (chi(2) = 7.192, p = 0.007). The G/G genotype significantly reduced risk for the development of ESCC compared to the combination of G/A and A/A genotypes (adjusted odds ratio [OR] = 0.37, 95% confidence interval [CI] = 0.16-0.83). After stratification according to smoking status, the A/A frequency among smoking ESCC (34.3%) and CAC patients (35.7%) was significantly higher than that among smoking healthy controls (18.6%) (chi(2) = 5.426 and 5.599, p = 0.020 and 0.018, respectively). Smokers with the A/A genotype had an about 2-fold increased risk for both of ESCC and CAC compared to the G/A and G/G genotypes, with an adjusted OR of 2.26 in ESCC (95% CI = 1.14-4.49) and of 2.42 in CAC (95% CI = 1.17-4.98). No correlation between the cyclin D1 genotype and development of ESCC or CAC was found among nonsmokers. Determination of the cyclin D1 (G870A) single nucleotide polymorphism may be suitable to identify individuals with increased risk for ESCC or CAC in the northern Chinese population.     

Cyclin D1 gene polymorphism and susceptibility to lung cancer in a Chinese population

The objective was to study the relationship between cyclin D1 gene (CCND1) polymorphism and lung cancer in the Chinese population. Blood samples of 182 cases and 185 controls were collected from a hospital based case-control study. PCR-SSCP was used to examine the G/A polymorphism in exon 4 of CCND1. The results showed that the frequencies of the CCND1 AA, GA and GG genotypes were 31.3, 46.7 and 22.0% respectively in cases, and 21.1, 53.0 and 25.9 respectively in controls. Adjusted by age (in years), sex and smoking status, multivariate logistic regression analysis showed that the AA genotype was associated with a significantly increased risk (OR = 1.87, 95% CI 1.01-3.45) for lung cancer. In the stratification analysis, the CCND1 AA variant genotype was associated with increased risk in individuals who were 相似文献