MICB基因多态性与肺癌的易感关联性研究

目的:研究海南汉族人群MICB等位基因的多态性与肺癌易感性之间的关联性。方法:采用PCR-SSP(PCR sequence-specific primers)和PCR-SBT(PCR sequence-based typing)方法对样本MICB等位基因的多态性进行检测。结果:肺癌患者中检出14种MICB等位基因;和对照组相比较,MICB*00502等位基因在肺癌患者组分布频率较少(43.5%vs 57.8%),MICB*016等位基因在肺癌患者组分布较多(5.9%vs 0.6%);MICB*016等位基因可能对肺癌易感(OR=11.19,95%CI:2.59-48.24,Pc0.05);MICB*00502等位基因可能对肺癌不易感(MICB*00502:OR=0.56,95%CI:0.42-0.76,Pc0.05)。结论:MICB等位基因的多态性与肺癌的易感性之间存在关联性。     

MICA基因多态性与海南人群HBV易感关联性研究

研究MICA等位基因多态性与海南人群HBV感染易感性之间的关联性。采用PCR-SSP和PCR-SBT方法对样本MICA等位基因的多态性进行检测。HBV感染患者中共检出10种MICA等位基因和5种MICA-STR等位基因,和对照组相比较,MICA*010、MICA-A5等位基因可能对HBV感染易感(MICA*010:OR=3. 88,95%CI:2. 19～6. 85,P=0. 000; MICA-A5:OR=1. 27,95%CI:0. 92～1. 77,P=0. 0068)。MICA*008/045基因型可能对HBV感染不易感,MICA*010/010纯合子基因型可能对HBV易感(MICA*008/045:OR=0. 09,95%CI:0. 01～1. 74,P=0. 0071; MICA*010/010:OR=4. 41,95%CI:1. 26～15. 46,P=0. 0106)。MICA等位基因多态性与海南人群HBV感染的易感性间存在关联性。     

乳腺癌与MICA基因多态性的相关性研究

目的:研究海南汉族人群MICA等位基因的多态性与乳腺癌的相关性。方法:采用PCR-SSP和PCRSBT方法对样本MICA等位基因的多态性进行检测分析。结果:乳腺癌患者中有检测出10种MICA等位基因,其中MICA*002/019基因型频率较对照组显著偏低(OR=0.32,Pc0.05)。结论:MICA*002/019基因型可能与乳腺癌的保护相关。     

湖南汉族人群MICB等位基因多态性与白血病的相关性研究

目的:研究湖南汉族人群MICB等位基因的多态性与白血病的相关性。方法:MICB等位基因分型用PCR-SSP和PCR-SBT的方法。结果:白血病患者中有13种MICB等位基因被检测出,其中MICB*005:02/010基因频率较对照组显著偏低(OR=0.416,P<0.05)。不同类别白血病之间MICB等位基因多态性没有显著差异。结论:MICB*005:02/010等位基因可能与白血病的保护相关。     

贵州侗族人群MICB等位基因多态性研究

目的:探讨贵州侗族健康人群MICB等位基因的分布特点。方法:收集100例健康无亲缘关系的贵州侗族人新鲜血液样本,采用世界卫生组织(WHO)推荐的标准盐析法从样本新鲜血液中提取基因组DNA,并用PCR-SSP、PCR-SBT两种方法对样本DNA进行MICB等位基因分型。结果:在贵州侗族人群中,检出7种MICB等位基因,其中MICB*005:02等位基因频率最高,其频率为58.50%,其次为MICB*002:01等位基因频率22.00%;而MICB*003及MICB*005:03等位基因频率最低,两者频率分别为1.50%。结论:贵州侗族人群MICB等位基因具有高度的多态性,该数据为研究MICB基因在同种异体器官移植和疾病易感性中的可能作用奠定了实验基础。     

MICA/B基因多态性与血吸虫病相关性研究

本研究采用PCR-SSP与PCR-SBT方法对正常健康对照组与血吸虫病感染组、血吸虫病性重度肝纤维化病人组和轻度肝纤维化病人组中MICA/B基因进行分型,并比较各组基因的多态性。结果在血吸虫感染组与健康对照组中共发现13种MICA等位基因和5种MICA-STR基因型,MICA*012:01(11.58%vs 5.83%)、MI-CA*017(2.11%vs 0.00%)及MICA*027(3.16%vs 0.97%)在对照人群组较血吸虫病人组中分布频率较高,但Pc值显示没有统计学意义(Pc>0.05)。MICA-STR型别分析显示,MICA-STR与血吸虫病易感没有相关性,但MICA*A5基因型的分布频率在重度肝纤维化组显著高于轻度肝纤维化组(45.10%vs 26.92%,Pc<0.05)。在血吸虫病人组中一共检出10种MICB等位基因。在本研究人群中未发现与日本血吸虫感染显著相关的MICB等位基因。同时MICB等位基因多态性在重度纤维化组、轻度纤维化组、以及正常对照组相互之间均无显著的相关性。研究显示在血吸虫病人组中,MICA和MICB具有连锁不平衡,其中单倍型MICB*008-MICA*002:01和MICB*014-MICA*045在血吸虫病人组中显示具有显著的连锁不平衡。     

CISH基因多态性与结核病易感性的相关性研究

目的:寻找肺结核的易感位点,探索宿主遗传因素差异对肺结核发病的影响,为肺结核的预防和药物研发提供理论依据。方法:对1218名汉族居民进行病例对照研究,其中病例组600例,对照组618例,进行流行病学调查和生化指标检查。运用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术检测CISH基因rs2239751和rs622502的基因型分布,探讨CISH基因多态性与中国汉族人群肺结核易感性的关联性。结果:CISH基因的rs2239751和rs622502等位基因分布均符合Hardy-Weinberg(H-W)遗传平衡定律(P0.05)。rs2239751位点基因型和等位基因分布在两组间差异有统计学意义,P值分别为0.013和0.01,并且携带C等位基因个体患肺结核的风险是携带A等位基因的个体1.16倍(95%CI=1.03-1.29,P=0.01)。rs2239751基因分型结果在女性病例组和对照组中差异有统计学意义,P值为0.007,OR(95%CI)为1.51(1.12-2.03)。rs2239751基因分型结果在45岁人群病例组和对照组中差异有统计学意义,P值为0.010,OR(95%CI)为1.32(1.07-1.64)。rs622502位点基因型和等位基因分布在两组间差异均无统计学意义(P0.05)。结论:在汉族人群中,rs2239751位点多态性可能是肺结核的危险因素之一,C等位基因为风险等位基因。rs2239751基因多态性与肺结核的关联性仅限于于女性和45岁人群。rs622502位点多态性可能与肺结核无关。     

CYP1A1、CYP1B1、NET、DAT1单个和联合基因型与汉族人群乳腺癌易感性的研究（英文）

乳腺癌是最常见的女性癌症,其发生是遗传因素和环境因素相互作用的结果。因此,我们就CYP1A1MspⅠ(m1多态)、CYP1B1 Leu432Val、NET T-182C、DAT1-VNTR等基因多态性对新疆汉族人群乳腺癌易感性的研究进行探讨。在以144例乳腺癌患者和120例正常对照组为研究对象的病例-对照研究中,发现CYP1A1MspⅠ位点CC基因型、C等位基因(OR=3.32,95%CI:1.24~8.86;OR=1.58,95%CI:1.09~2.31)和高风险联合基因型CYP1A1 MspⅠ与CYP1B1 Leu432Val,CYP1A1 MspⅠ与DAT1-VNTR,CYP1B1 Leu432Val与DAT1-VNTR(OR=2.43,95%CI:1.23~4.78;OR=4.53,95%CI:1.26~16.27;OR=2.98,95%CI:1.10~8.06)与乳腺癌风险增加有关。CYP1B1、NET和DAT1基因多态性与乳腺癌易感性无关。这些研究结果表明,CYP1A1 MspⅠ多态性和CYP1A1、CYP1B1、DAT1高风险联合基因型能增加新疆汉族人群患乳腺癌的风险。     

eNOS基因（894G／T）多态性与HBV感染

为探讨HBV感染临床转归与eNOS基因多态性的关系,选择传染科门诊及住院部2002.2-2004.2诊治的无亲缘关系的重庆地区汉族居民2400人,采用聚合酶链反应(PCR)及限制性内切酶技术检测eNOS exon7位点894G/T多态性,应用SPSS软件χ2检验进行统计学处理:首先Hardy-Weinberg平衡检验Pa>0.01,表明拟合度优良,收集病例有良好的代表性;其次乙肝病毒携带与其余任何组比较(急乙肝与肝癌组因例数太少除外)等位基因频率与基因型频率Pb<0.05,乙肝病毒携带 慢乙肝组与肝硬化 重症肝炎组等位基因频率与基因型频率比较Pb<0.05。以非条件logistic回归校正年龄及性别因素进行分层分析,在隐性模式和共显性模式下,eNOS基因位点894G/T SNP与HBV感染后疾病的携带状态显著关联。与894G/T和T/T基因型相比,G/G基因型的个体发展为携带状态的易感性显著增高(隐性模式:OR=1.428 95%CI=1.050-1.942;共显性模式:OR=1.310 95%CI=1.025-1.676)。     

E 选择素基因多态性与新疆哈萨克族患者脑梗死的关系

目的:探讨E一选择素(E-selectin)基因多态性与新疆哈萨克族患者脑梗死(cebreral infarction,CI)的关系。方法:采用聚合酶链反应一限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)和DNA序列测定法检测103例CI及110例对照组E-selectin基因第4外显子A561C(S128R)、第10外显子C1839T(L554F)多态性。结果:E-se-lectin基因S128R基因型频率和等位基因频率在CI组和对照组比较差异有显著性(P<0.05),基因型频率的相对风险分析发现,SR基因型携带者患CI的风险是SS基因型的2.355倍(OR=2.355,95%CI:1.209～4.588);E-selectin L554F基因型在两组中的分布差异有显著性(X2=5.463,P<0.05),基因型频率的相对风险分析,LF基因型患CI的风险是LL基因型的2.315倍(OR=2.315,95%CI:1.132～4.737)。结论:E-selectin S128R和L554F多态性与脑梗死易感性有关;R等位基因和F等位基因可能是新疆哈萨克族CI发病的遗传易感基因。     

Transforming growth factor β signaling pathway associated gene polymorphisms may explain lower breast cancer risk in western Indian women

Transforming growth factor β1 (TGFB1) T29C and TGF β receptor type 1 (TGFBR1) 6A/9A polymorphisms have been implicated in the modulation of risk for breast cancer in Caucasian women. We analyzed these polymorphisms and combinations of their genotypes, in pre menopausal breast cancer patients (N = 182) and healthy women (N = 236) from western India as well as in breast cancer patients and healthy women from the Parsi community (N = 48 & 171, respectively). Western Indian women were characterized by a higher frequency of TGFB1*C allele of the TGF β T29C polymorphism (0.48 vs 0.44) and a significantly lower frequency of TGFBR1*6A allele of the TGFBR1 6A/9A polymorphism (0.02 vs 0.068, p<0.01) as compared to healthy Parsi women. A strong protective effect of TGFB1*29C allele was seen in younger western Indian women (<40 yrs; OR = 0.45, 95% CI 0.25-0.81). Compared to healthy women, the strikingly higher frequencies of low or intermediate TGF β signalers in patients suggested a strong influence of the combination of these genotypes on the risk for breast cancer in Parsi women (for intermediate signalers, OR = 4.47 95%CI 1.01-19.69). The frequency of low signalers in Parsi healthy women, while comparable to that reported in Europeans and Americans, was three times higher than that in healthy women from western India (10.6% vs 3.3%, p<0.01). These observations, in conjunction with the low incidence rate of breast cancer in Indian women compared to White women, raise a possibility that the higher frequency of TGFB1*29C allele and lower frequency of TGFBR1*6A allele may represent important genetic determinants that together contribute to a lower risk of breast cancer in western Indian women.     

DNA repair genetic polymorphisms and risk of colorectal cancer in the Czech Republic

Colorectal cancer represents a complex disease where susceptibility may be influenced by genetic polymorphisms in the DNA repair system. In the present study we investigated the role of nine single nucleotide polymorphisms in eight DNA repair genes on the risk of colorectal cancer in a hospital-based case-control population (532 cases and 532 sex- and age-matched controls). Data analysis showed that the variant allele homozygotes for the Asn148Glu polymorphism in the APE1 gene were at a statistically non-significant increased risk of colorectal cancer. The risk was more pronounced for colon cancer (odds ratio, OR: 1.50; 95% confidence interval, CI: 1.01-2.22; p=0.05). The data stratification showed increased risk of colorectal cancer in the age group 64-86 years in both individuals heterozygous (OR: 1.79; 95% CI: 1.04-3.07; p=0.04) and homozygous (OR: 2.57; 95% CI: 1.30-5.06; p=0.007) for the variant allele of the APE1 Asn148Glu polymorphism. Smokers homozygous for the variant allele of the hOGG1 Ser326Cys polymorphism showed increased risk of colorectal cancer (OR: 4.17; 95% CI: 1.17-15.54; p=0.03). The analysis of binary genotype combinations showed increased colorectal cancer risk in individuals simultaneously homozygous for the variant alleles of APE1 Asn148Glu and hOGG1 Ser326Cys (OR: 6.37; 95% CI: 1.40-29.02; p=0.02). Considering the subtle effect of the DNA repair polymorphisms on the risk of colorectal cancer, exploration of gene-gene and gene-environmental interactions with a large sample size with sufficient statistical power are recommended.     

Susceptibility of XPD and RAD51 genetic variants to carcinoma of urinary bladder in North Indian population

For the present study, two polymorphisms, xeroderma pigmentosum, complementation group D (XPD) Lys751Gln and RAD51 135G/C were studied with regard to bladder cancer. For XPD Lys751Gln polymorphism, an increased risk of bladder cancer was found to be associated with the Gln variant allele (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.27-2.73), on taking AA (Lys/Lys) as the referent genotype. In males, the XPD 751C (Gln) allele was found to be associated with a significantly increased risk (OR=2.33, 95% CI=1.52-3.56). The inhabitants of rural areas showed a significantly increased risk with the XPD Gln allele (OR=2.59, 95% CI=1.46-4.62) when compared with those of urban areas. In smokers (OR=5.30, 95% CI=2.42-11.68), alcohol drinkers (OR=4.33, 95% CI=2.17-8.70), and nonvegetarians (OR=2.21, 95% CI=1.26-3.87), the XPD Gln allele showed a significantly increased risk toward bladder cancer. For RAD51 135G/C polymorphism, no significant difference was observed in the allelic and genotypic frequencies. Even after stratification, no significant association could be seen. After stratifying histopathologically, the RAD51 CC genotype was associted with decreased risk in subjects having superficial stage (OR=0.51, 95% CI=0.27-0.99) and with those having G2 grade (OR=0.24, 95% CI=0.09-0.62) of bladder cancer. XPD polymorphism may be a predisposing factor, but the same cannot be said for RAD51 gene polymorphism.     

The Association between NQO1 Pro187Ser Polymorphism and Bladder Cancer Susceptibility: A Meta-Analysis of 15 Studies

Background

NAD(P)H:quinone oxidoreductase 1 (NQO1), an obligate two-electron reductase, plays an important role in reducing reactive quinones to less reactive and less toxic hydroquinones. Genetic variations in NQO1 gene that impede its enzyme function may be considered as putative risk factor for cancer. Numerous studies have been performed to investigate the association between NQO1 Pro187Ser polymorphism and bladder cancer risk; nevertheless, the results remain controversial.

Methods

We indentified eligible publications from PubMed, Embase and CBM databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to access the strength of the associations. False-positive report probability (FPRP) analysis was also performed for all statistically significant findings.

Results

We collected a total of 15 studies including 4298 cases and 4275 controls in the final meta-analysis. Overall, the NQO1 187Ser carriers were associated with an increased bladder cancer risk (homozygous: OR = 1.43, 95% CI = 1.08-1.90; recessive: OR = 1.33, 95% CI = 1.03-1.72; dominant: OR = 1.19, 95% CI = 1.04-1.37, and allele comparing: OR = 1.18, 95% CI = 1.06-1.33). Stratification analyses showed a statistically significant association among Asians (homozygous: OR = 1.82, 95% CI = 1.39-2.38; recessive: OR = 1.52, 95% CI = 1.20-1.93, dominant: OR = 1.40, 95% CI = 1.05-1.88, and allele comparing: OR = 1.35, 95% CI = 1.15-1.58), never smokers (homozygous: OR = 2.30, 95% CI = 1.14-4.65; heterozygous: OR = 2.26, 95% CI = 1.43-3.56; dominant model: OR = 1.59, 95% CI = 1.14-2.21, and allele comparing: OR = 1.72, 95% CI = 1.27-2.33), hospital-based studies (homozygous: OR = 1.46, 95% CI = 1.09-1.94; recessive: OR = 1.32, 95% CI = 1.02-1.69; dominant: OR = 1.28, 95% CI = 1.05-1.56, and allele comparing: OR = 1.24, 95% CI = 1.07-1.43), studies with genotyping performed by PCR-RFLP under all genetic models, and studies with minor allele frequency >0.30 (homozygous: OR = 1.69, 95% CI = 1.25-2.27; recessive: OR = 1.46, 95% CI = 1.10-1.95, and allele comparing: OR = 1.25, 95% CI = 1.04-1.51), respectively.

Conclusions

Despite some limitations, our meta-analysis provides sufficient evidence that NQO1 Pro187Ser polymorphism may contribute to bladder cancer risk. These findings need further validation in well-designed prospective studies with larger sample size and different ethnicities, especially for Asians.     

The XRCC3 Thr241Met polymorphism and breast cancer risk: a case-control study in a Thai population

The X-ray repair cross-complementing group 3 gene (XRCC3) belongs to a family of genes responsible for repairing DNA double-strand breaks caused by normal metabolic processes and exposure to ionizing radiation. Polymorphisms in DNA repair genes may alter an individual's capacity to repair damaged DNA and may lead to genetic instability and contribute to malignant transformation. We examined the role of a polymorphism in the XRCC3 gene (rs861529; codon 241: threonine to methionine change) in determining breast cancer risk in Thai women. The study population consisted of 507 breast cancer cases and 425 healthy women. The polymorphism was analysed by fluorescence-based melting curve analysis. The XRCC3 241Met allele was found to be uncommon in the Thai population (frequency 0.07 among cases and 0.05 among controls). Odds ratios (OR) adjusted for age, body mass index, age at menarche, family history of breast cancer, menopausal status, reproduction parameters, use of contraceptives, tobacco smoking, involuntary tobacco smoking, alcohol drinking, and education were calculated for the entire population as well as for pre- and postmenopausal women. There was a significant association between 241Met carrier status and breast cancer risk (OR 1.58, 95% confidence interval (CI) 1.02-2.44). Among postmenopausal women, a slightly higher OR (1.82, 95% CI 0.95-3.51) was found than among premenopausal women (OR 1.48, 95% CI 0.82-2.69). Our findings suggest that the XRCC3 Thr241Met polymorphism is likely to play a modifying role in the individual susceptibility to breast cancer among Thai women as already shown for women of European ancestry.     

Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in cancer: a meta-analysis

Toll-like receptor 4 (TLR4) is critical in the recognition of Gram-negative bacteria serving as a key immune system effector. Recently, a number of case-control studies were conducted to investigate the association between TLR4 gene polymorphism and cancer risk, especially Asp299Gly and Thr399Ile polymorphisms. However, published data were still conflicting. In this paper, we summarized 9463 cancer cases and 10,825 controls from 22 studies and attempted to assess the susceptibility of TLR4 gene polymorphism to cancers by a synthetical meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. Our results suggested that Asp299Gly represented a risk factor on cancers in digestive system (G allele versus A allele, OR=1.64, 95% CI: 1.02-2.64; GA+GG versus AA, OR=1.64, 95% CI: 1.00-2.71) but tend to have a protective effect on prostate cancer (GG versus AA, OR=0.37, 95% CI: 0.14-0.98; GG versus GA+AA, OR=0.37, 95% CI: 0.14-0.98). Thr399Ile polymorphism was significantly associated with an elevated cancer risk in overall analysis (T allele versus C allele, OR=1.72, 95% CI: 1.27-2.33; TC versus CC, OR=1.63, 95% CI: 1.18-2.26; TT+TC versus CC, OR=1.70, 95% CI: 1.24-2.34) and especially in gastrointestinal subgroup (T allele versus C allele, OR=2.01, 95% CI: 1.40-2.89; TC versus CC, OR=1.86, 95% CI: 1.26-2.74; TT+TC versus CC, OR=1.97, 95% CI: 1.35-2.88). Further prospective researches with larger numbers of worldwide participants are warranted to draw comprehensive and true conclusions.     

HIF-1α 1772 C/T and 1790 G/A Polymorphisms Are Significantly Associated with Higher Cancer Risk: An Updated Meta-Analysis from 34 Case-Control Studies

Background

HIF-1 activates various genes in cancer progression and metastasis. HIF-1α 1772 C/T and 1790 G/A polymorphisms are reportedly associated with cancer risk; however, the results are inconclusive.

Methodology/Principal Findings

A meta-analysis of 34 studies that involved 7522 cases and 9847 controls for 1772 C/T and 24 studies that involved 4884 cases and 8154 controls for 1790 G/A was conducted to identify the association of C/T and G/A polymorphisms with cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association.HIF-1α 1772 C/T and 1790 G/A polymorphisms were associated with higher cancer risk in homozygote comparison (1772C/T: TT vs. CC: OR = 2.45, 95% CI: 1.52, 3.96; P _{heterogeneity} = 0.028; 1790G/A: AA vs. GG: OR=4.74, 95% CI: 1.78, 12.6; P _{heterogeneity} < 0.01), dominant model (1772C/T: TT/CT vs. CC: OR = 1.27, 95% CI: 1.04, 1.55; P _{heterogeneity} < 0.01, 1790G/A: AA/GA vs. GG: OR = 1.65, 95% CI: 1.05, 2.60; P _{heterogeneity} < 0.01), T allele versus C allele (T vs. C: OR = 1.42, 95% CI: 1.18, 1.70; P _{heterogeneity} < 0.01), and A allele versus G allele (A vs. G: OR = 1.83, 95% CI: 1.13, 2.96; P _{heterogeneity} < 0.01). On a subgroup analysis, the 1772 C/T polymorphism was significantly linked to higher risks for breast cancer, lung cancer, prostate cancer, and cervical cancer, whereas the 1790 G/A polymorphism was significantly linked to higher risks for lung cancer and prostate cancer. A significantly increased cancer risk was found in both Asians and Caucasians for 1772C/T polymorphism, whereas a significantly increased cancer risk was found in Caucasians in the heterozygote comparison and recessive model for 1790G/A polymorphism.

Conclusions

HIF-1α 1772 C/T and 1790 G/A polymorphisms are significantly associated with higher cancer risk.     

Effect of point substitutions in the MnSOD, GPX1, and GSTP1 genes on the risk of familial and sporadic breast cancers in residents of the Altaĭ region of the Russian Federation

The frequencies of the polymorphic gene variants MnSOD Ala9Val, GPX1 Pro198Leu, and GSTP1 Ile105 Val were estimated in female residents of Altai krai with breast cancer. The frequency distributions of the genotypes for all genes studied in both patients and control subjects fit the Hardy-Weinberg equilibrium. The estimated frequencies of the genotypes for the studied genes in the control group did not differ from those earlier reported for Caucasoid women living in Europe. The T(rs1050450) allele of the GPX1 gene was demonstrated to protect against sporadic breast cancer (OR = 0.74 (95% CI = 0.58-0.94), p = 0.012). Carriers of the genotype combination MnSOD CC + GPX1 CC were found to have a 1.6 times higher risk of sporadic breast cancer compared to the control group (OR = 1.59 (1.05-2.41), p = 0.0258). The polymorphic loci GSTP1 (rs1695) and MnSOD (rs4880) were not found to be significantly associated with the risk of familial or sporadic breast cancer.