IGF-1和IGFBP-3基因多态性与非吸烟女性肺癌关联研究

  目的   探讨胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子结合蛋白-3（IGFBP-3）单核苷酸多态性与非吸烟女性肺癌发病的关系。   方法   采用TaqMan单核苷酸多态性分型技术,检测287例中国汉族女性肺癌患者和281例正常女性对照者IGF-1和IGFBP-3基因位点的基因型。   结果   IGF-1基因rs2946834位点的三种基因型（CC/CT/TT）在女性非吸烟肺癌患者和对照间的分布具有显著性差异（P < 0.001）,与TT基因型相比,CC基因型显著降低女性肺癌的发病风险（OR=0.28,95%CI:0.15~ 0.54）。另外,在非吸烟女性中,IGF-1（rs1520220）GG基因型可降低晚期肺癌发病风险（OR=0.30,95%CI:0.09~0.96）。   结论   IGF-1基因单核苷酸多态性可能与女性非吸烟肺癌的发病相关,这一结论有待于大样本以及功能学研究的进一步证实。      

IGF-1R基因多态性与原发性肝癌易感性的相关性研究

目的 探讨广西肝癌高发区肝癌相关基因IGF-1R基因多态性与原发性肝癌易感性的关系.方法 采用病例对照研究方法,在广西肝癌高发现场人群中选取113例原发性肝癌及113名健康对照人群.以筛选IGF-1R基因SNP rs 61740868位点为遗传标志,采用聚合酶链式反应-限制性片段长度多态性方法(PCR-RFLP法)检测IGF-1R基因rs 61740868多态性及其基因分布的频率.结果 肝癌病例组与对照组IGF-I R基因rs 61740868位点均未发生基因突变,其基因型均为CC型,两组比较差异无统计学意义(P＞0.05).结论 IGF-1R基因rs 61740868位点多态性与肝癌发生无关,可能不是肝癌的危险因素之一.     

结直肠癌组织IGF-1和IGFBP-3表达临床意义分析

目的：探讨IGF-1和IGFBP-3在结直肠癌（colorectalcancer,CRC）组织中的表达及其临床意义。方法：选取承德医学院附属保定市第-中心医院2005-06—13—2012—12—27接受手术治疗的CRC患者183例作为观察组,并对其中61例取其癌旁正常黏膜组织作为对照组,应用免疫组化SP法分别检测IGF-1和IGFBP-3在两组的表达情况。结果：IGF-1在CRC中的阳性表达率60．1％（110／183）,显著高于对照组31．1％（19／61）,P〈0．001;IGFBP-3在CRC中的阳性表达率78．1％（143／183）,显著低于对照组95．1％（58／61）,P=0．003。IGF-1表达与组织学分级、浸润深度、TNM分期和淋巴结转移有关,P〈0．05;IGFBP-3表达与TNM分期和淋巴结转移有关,P〈0．05;两者与年龄、性别、肿瘤大小、部位和远处转移等均无关,P〉0．05。IGF-1与IGFBP-3表达呈较弱的负相关性,r=-0．188,P-0．011。Logistic多因素回归分析显示,IGF-1在CRC中高表达是TNM分期增高和淋巴结转移的危险因素之一,IGFBP-3低表达是CRC发生淋巴结转移的危险因素之一。结论：IGF-1和IGFBP-3异常表达在CRC的发生发展过程中起重要作用,联合检测IGF-1和IGFBP-3可能成为临床上cRC评估预后新的生物学指标。     

ADIPOQ基因多态性与前列腺癌易感性的相关性研究

背景与目的：环境因素在前列腺癌发病机制中的作用,尤其是高脂肪摄入饮食、缺乏体力活动等引起的肥胖逐渐受到重视。脂联素可能是前列腺癌与肥胖之间潜在的分子递质,本研究旨在探讨编码脂联素的ADIPOQ基因多态性与中国人群前列腺癌发病风险的关联性。方法：提取917例前列腺癌患者和1 036例正常对照男性的外周血DNA,通过TaqMan探针技术检测ADIPOQ基因rs266729和rs182052的多态性。采用Logistic回归模型分析各基因型与前列腺癌发病风险的关系,在此基础上分析其与体质量指数的关系。结果：对照组中rs266729和rs182052两位点的基因型频率均符合Hardy-Weinberg平衡（P=0.29和0.83）。rs266729和rs182052两位点各基因型在两组间的分布差异无统计学意义（P=0.88和0.63）。与野生型相比,两位点的杂合型及突变型携带者患病风险差异无统计学意义（OR=0.97,95%CI：0.81~1.16;OR=0.89,95%CI：0.73~1.09）。分层分析显示,在年龄≤69岁的人群中,rs182052 AA基因型携带者的前列腺癌发病风险仅为AG或GG基因型携带者的73%（95%CI：0.54~0.99）,差异有统计学意义（P=0.04）。rs182052遗传变异与体质量指数相关（P=0.03）。结论：ADIPOQ基因rs266729和rs182052可能与中国人群前列腺癌总体发病风险无关,rs182052 AA基因型携带者≤69岁时发病风险较低,并且该位点的遗传变异与前列腺癌患者的体质量指数相关。     

CAV-1基因多态性与散发乳腺癌易感性的相关性分析

[目的]探讨CAV-1基因多态性与散发乳腺癌的相关性。[方法]采用病例对照研究,纳入经病理确诊的135例女性乳腺癌患者作为实验组,166例女性健康体检者为对照组。通过竞争性等位基因特异性PCR法对研究对象基因位点进行分型;采用χ2检验比较CAV-1各SNP基因型及等位基因频率在两组中的分布差异;非条件Logistic回归分析CAV-1基因多态性与乳腺癌易感性的关联。[结果]在共显性模型、显性模型及等位基因模型下rs3807987及rs7804372位点多态性与乳腺癌易感性密切相关。rs3807987:相对于GG基因型,AG、AA基因携带者(AG/AA基因型)均增加乳腺癌的发病风险(P<0.05),OR值分别为2.110(95%CI:1.270~3.505)、1.968(95%CI:1.205~3.216)。rs7804372位点:相对于TT基因型,AT、AA基因携带者(AT/AA基因型)均增加乳腺癌的发病风险(P<0.05),OR值分别为2.088(95%CI:1.285~3.392)、2.059(95%CI:1.293~3.280)。rs12672038位点:在共显性模型、显性模型、等位基因模型均未见rs12672038位点多态性分布与乳腺癌发病风险之间存在相关性。[结论]CAV-1基因rs3807987与rs7804372多态性与乳腺癌易感性相关。     

NQO1基因多态性与肺癌遗传易感性

目的：探讨依赖还原型辅酶１／２醌氧化还原的酶基因ｃＤＮＡ６００位Ｃ→Ｔ点突变怕致物基因多态必理否与肺癌遗传多态性有关。方法：采用聚合酶锭反应－限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）的分析方法分析队列 肺癌病人与１３６例健康成人对照组ＮＱＯ１的基因多态性。结果：Ｔ等位基因频率在肺癌组和对照组分别为５４％、４３％,两组有显著差异（Ｐ＝０．０２４）。基因型分布在肺癌组和组之间差异显著（Ｐ＝０．００８）     

生物钟PER3基因多态性与乳腺癌易感性的相关性研究

[目的]探讨参与生物节律调控的生物钟PER3基因多态性与乳腺癌易感性的关系.[方法] 2005年9月至2008年2月,836例乳腺癌患者和946名健康对照者,采用PCR技术对PER3基因多态性进行检测,分析两组PER3基因型的分布及PER3基因多态性与乳腺癌发病风险的关系.[结果]对照组PER3-/-、+/+和+/-基因型分布频率分别为72.73％、1.59％和25.69％,病例组分别为72.61％、1.79％和25.60％,两组分布差异无统计学意义(P=0.9432).经相关因素调整后,PER3基因型与乳腺癌发病风险相关性分析显示,携带PER3+/+基因型发生乳腺癌的危险是携带PER3-/-基因型的3.503倍(95％CI:1.069～11.480),是携带PER3+/-或PER3-/-基因型对象的3.337倍(95％CI:1.025～10.864).[结论]PER3+/+基因型能够增加乳腺癌的发病风险,是乳腺癌发生的独立危险因素.     

谷胱甘肽硫转移酶A1(GSTA1)基因多态性与前列腺癌和膀胱癌易感性的Meta分析

目的 探讨谷胱甘肽硫转移酶A1(GSTA1)基因多态性与前列腺癌及膀胱癌易感性的关系.方法 通过检索PubMed等数据库,获取GSTA1基因多态性与前列腺癌或膀胱癌的文献9篇,对1989例病例和2246例对照进行meta分析,以比值比(OR)和95%可信区间(CI)作为效应指标.结果 各遗传模型的Meta分析显示:GSTA1基因多态性与前列腺癌易感性的相关性无统计学意义[(AA vs BB:OR=0.92,95%CI:0.68~1.23,P=0.56);(AB vs BB:OR=1.02,95%CI:0.86~1.21,P=0.83);(AA/AB vs BB OR=1.01,95%CI:0.86~1.17,P=0.93);(AA vs AB/BB:OR=0.91,95%CI:0.69~1.20,P=0.51)].各遗传模型的Meta分析显示:GSTA1基因多态性与膀胱癌易感性的相关性无统计学意义[(AA vs BB:OR=0.97,95%CI:0.71~1.33,P=0.85);(AB vs BB:OR=1.11,95%CI:0.93~1.31,P=0.25);(AA/AB vs BB OR=1.07,95%CI:0.92~1.25,P=0.37);(AA vs AB/BB:OR=0.87,95%CI:0.64~1.18,P=0.37)].结论 单独的GSTA1基因多态性不是前列腺癌和膀胱癌的易感因素.     

2型糖尿病合并胃癌患者血清IGF-1、IGFBP-3的变化

目的:研究2型糖尿病（diabetes mellitus,DM）合并胃癌（gastric cancer,GC）患者血清胰岛素样生长因子-1（insulin-like growth factor-1,IGF-1）、胰岛素样生长因子结合蛋白-3(insulin-like growth factor binding protein-3,IGFBP-3)的变化。方法:选择2型DM患者30例（DM组）、2型DM合并GC患者48例（DM并GC组）为研究对象,ELISA 法测定血清IGF-1、 IGFBP-3水平;同时测定空腹血糖、空腹胰岛素、血脂水平。 结果:DM并GC组的IGF-1、IGF-1/IGFBP-3比值高于DM组（P<0.05）,IGFBP-3在两组之间无统计学差异（P>0.05）。IGF-1、IGF-1/IGFBP-3比值与空腹胰岛素水平呈正相关（r=0.598,0.626,P=0.000）,IGF-1/IGFBP-3比值是DM并GC患者淋巴结转移的危险因素（OR=2.142,P=0.001）。结论:IGF-1可能参与2型DM合并GC的发生及淋巴结转移。     

IGF-1、IGFBP-3在非小细胞肺癌组织中的表达及其临床意义

目的 探讨类胰岛素一号生长因子(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)在非小细胞肺癌(NSCLC)患者血清和肺癌组织中的表达及临床意义。方法 收集98例NSCLC纳入观察组,同时收集肺部良性病变40例纳入对照组。统计两组血清及肺癌组织中IGF-1、IGFBP-3表达。结果 观察组血清IGF-1水平高于对照组,IGFBP-3水平低于对照组,P<0.05。血清IGF-1、IGFBP-3水平与TNM分期、淋巴结转移、局部侵犯有关,P<0.05。观察组IGF-1阳性表达率显著高于对照组,IGFBP-3阳性表达率显著低于对照组,P<0.05。IGF-1、IGFBP-3阳性表达率与TNM分期、淋巴结转移、局部侵犯有关,P<0.05。血清IGF-1诊断NSCLC AUC为0.733,灵敏度55.5%,特异度91.2%,最佳截断值150.26μg/L;血清IGFBP-3诊断NSCLC AUC为0.799,灵敏度63.6%,特异度78.6%,最佳截断值1413.54μg/L。结论 NSCLC患者血清IGF-1、IGFBP-3主要与TNM分期、淋巴结转移及局部...     

Genetic polymorphisms in APE1 are associated with renal cell carcinoma risk in a Chinese population

Apurinic/apyrimidinic endonuclease 1 (APE1) is a DNA repair protein, which plays important roles in the base excision repair (BER) pathway. Genetic variations of APE1 have been shown to influence an individual's susceptibility to carcinogenesis. We hypothesized the genetic polymorphisms of APE1 are associated with the risk of renal cell carcinoma (RCC). In a case-control study of 612 RCC patients and 632 age and sex matched healthy controls, we genotyped two APE1 functional polymorphisms (-656 T>G, rs1760944 and 1349 T>G, rs1130409) and assessed their associations with risk of RCC. We found that, compared with 1349 TT/TG genotypes, the variant genotype 1349 GG had a significantly increased RCC risk [adjusted odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.10-1.95], particularly among subgroups of BMI > 23 kg/m(2) (OR = 1.54, 95% CI = 1.06-2.22), male (OR = 1.70, 95% CI = 1.17-2.46), never smokers (OR = 1.56, 95% CI = 1.11-2.21), light smokers (OR = 2.01, 95%CI = 1.02-3.95), and drinkers (OR = 2.00, 95% CI = 1.13-3.54). Furthermore, the polymorphism was significantly associated with risk of developing localized stage RCC. No altered RCC risk was associated with the -656 T>G polymorphism, but we found individuals who were homozygous for both risk alleles of the two SNPs had a 2.17-fold increased risk for RCC, compared to individuals with 0 risk alleles. Our results suggest that polymorphisms of APE1 may confer susceptibility to RCC.     

Genetic polymorphisms in XRCC1 associated with radiation therapy in prostate cancer

Radiation therapy is a potentially curative, important treatment option in localized prostate cancer. However, at 8 years after radiation therapy, even in the best risk subset of patients, approximately 10% of patients will experience clinical disease recurrence. The identification of molecular markers of treatment success or failure may allow for the development of strategies to further improve treatment outcomes. Herein, we investigated five molecular markers of DNA repair. 513 patients with castrate-resistant prostate cancer (CRPC), including 284 patients who received radiotherapy, 229 patients without radiotherapy and 152 healthy individuals were genotyped for five polymorphisms in DNA excision repair genes: ERCC1 N118N (500C>T), XPD K751Q (2282A>C), XRCC1 R194W (685C>T), XRCC1 R399Q (1301G>A) and PARP1 V762A (2446T>C). The distribution of genetic polymorphisms in the patients with CRPC and in healthy controls was compared, and the association between the polymorphisms and overall survival was investigated. The polymorphisms evaluated did not show differences between the patient group and the healthy controls, nor did they show a trend toward an association with survival. However, in the radiation treated subgroup, the median survival time was associated with the XRCC1 haplotype. The median survival time was 11.75 years for patients with the R399Q AA /R194W CC haplotype, 12.17 years for patients with the R399Q AG/R194W CC haplotype, 6.665 years for patients with the R399Q AG/R194W CT haplotype, and 6.21 years for patients with the R399Q GG/R194W CT haplotype (p = 0.034). This association was not found when all patients were investigated. We conclude that the genetic polymorphisms in XRCC1 may affect the outcome in patients who received radiotherapy for localized prostate cancer.Key words: DNA excision repair, BER, XRCC1, prostate cancer, radiotherapy, genetic polymorphism, haplotype     

Genetic polymorphisms in centrobin and Nek2 are associated with breast cancer susceptibility in a Chinese Han population

Centrosome aberrations have been suggested to cause chromosomal instability and aneuploidy, and eventually promote cancer development. The Centrobin and Nek2 proteins interact with each other and both are involved in centrosome duplication and chromosome segregation. This study aimed to investigate whether genetic polymorphisms in these two genes may affect breast cancer susceptibility in Chinese Han population using a haplotype-based analysis. Five single nucleotide polymorphisms (SNPs) in centrobin and four SNPs in Nek2 were genotyped in 1,215 cases of infiltrating ductal breast cancer and 1,215 age-matched cancer-free controls from Chinese Han population. The results showed that CATCG haplotype of centrobin was strongly associated with decreased breast cancer risk (adjusted OR = 0.14, 95 % CI = 0.09–0.22), which was mainly driven by the C allele of SNP rs11650083 (A>C, located in exon 12, resulting in Pro578Gln). None of the individual SNPs in Nek2 was associated with breast cancer risk. However, haplotype GTAT of Nek2 was associated with increased risk of breast cancer (adjusted OR = 1.56, 95 % CI = 1.18–2.06) and its risk was significantly elevated among women with both family history of cancer and a longer menarche-first full-term pregnancy (FFTP) interval (>11 years) (adjusted OR = 5.31, 95 % CI = 1.97–14.32). Furthermore, women harboring both at-risk haplotype GTAT of Nek2 and protective haplotype CATCG of centrobin were linked with decreased breast cancer risk, suggesting that the association between genetic variants of Nek2 and increased breast cancer risk was modified by genetic variants of centrobin. Our results indicate that genetic polymorphisms of centrobin and Nek2 are related to breast cancer susceptibility in Chinese Han women.     

Genetic variants of ESR1 and SGSM3 are associated with the susceptibility of breast cancer in the Chinese population

Background

The objective of this study was to investigate whether the genetic polymorphism rs12665607 of ESR1, rs10995190 of ZNF365, rs3817198 of LSP1 and rs17001868 of SGSM3/MKL1 are associated with the development of breast cancer (BC) in the Chinese women.

Methods

The 4 SNPs were genotyped for 453 female BC patients and 750 controls. The differences of genotype and allele distributions between patients and controls were evaluated using the Chi-square test. The comparison of SGSM3 expression in the tumor and the adjacent normal breast tissues was carried out by the Student’s t test. One-way ANOVA test was used to analyze the relationship between genotypes of rs17001868 and the tissue expression of SGSM3.

Results

Patients were found to have significantly higher allele T of rs12665607 and allele C of rs17001868 than that of the controls (35.2 % vs. 29.6 %, p = 0.004 for rs12665607; 23.1 % vs. 19.1 %, p = 0.02 for rs17001868). The OR values were 1.29 for rs12665607 and 1.27 for rs17001868, respectively. The mean expression level of SGSM3 was significantly lower in BC tumors than in the adjacent normal tissues (0.0082 ± 0.0038 vs. 0.0134 ± 0.0078; p < 0.001). Patients with genotype CC were found to have a remarkably lower SGSM3 expression in the tumors than those with genotype AA (p = 0.007).

Conclusions

ESR1 gene and the SGSM3 gene are associated with the risk of BC in Chinese population. Besides, rs17001868 may be a putative functional variant that can affect the expression of SGSM3 in patients with BC. With the OR ranging from 1.27 to 1.29, variants of these 2 genes can only explain limited variance of BC. Further investigations into the functional role of the susceptible genes would be helpful to clarify the etiology of BC.

     

PD-1 polymorphisms are associated with sporadic breast cancer in Chinese Han population of Northeast China

The programmed death-1 (PD-1) is a potent immunoregulatory molecule which is responsible for the negative regulation of T-cell activation and peripheral tolerance. In order to investigate the association between polymorphisms of PD-1 and breast cancer, a case–control study was conducted in Chinese female population consisting of 490 cases with breast cancer and 512 age-matched healthy individuals from Heilongjiang Province of China. Four polymorphisms of the PD-1 gene, including rs36084323 (PD-1.1), rs7421861, rs2227982 (PD-1.9), and rs2227981 (PD-1.5), were selected and genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of PD-1.1 GG genotype and PD-1.5 CT genotype were significantly lower in cases compared with controls (P = 0.020 and 0.004, respectively), and PD-1.5 CC genotype and C allele had higher frequencies in cases (P = 0.003 and 0.010). In haplotype analysis, we observed that the frequencies of ATTC and GTCT haplotypes were lower in cases than those of in controls (P = 0.0055 and 0.0012, respectively), whereas the GTCC and ATCC haplotypes had higher frequencies in cases (P = 0.0040 and 0.00008037, respectively). Additionally, strong association was showed between PD-1.1 and P53, and haplotype CCTA was associated with ER status. These results primarily suggest that PD-1 gene polymorphisms may affect the breast cancer risk and prognosis in Chinese Han females of Heilongjiang Province in Northeast China.     

IGF-1 and IGFBP-3 gene variants influence on serum levels and prostate cancer risk in African-Americans

Insulin-like growth factor (IGF)-1 and Insulin-like growth factor binding protein-3 (IGFBP-3) are strong inhibitors of apoptosis and play a role in mediating the effects of growth hormone. Both IGF-1 and IGFBP-3 serum levels have been linked to cancer risk. Here, we explore the relationship between three common IGF polymorphisms [C/T single-nucleotide polymorphism (SNP) (rs7965399) and a dinucleotide repeat (CA)n within the 5' regulatory region of the IGF-1 gene and the -202 A/C SNP in the IGFBP-3 gene], serum levels and prostate cancer (Pca) risk in 767 African-Americans enrolled in a clinic-based case-control study. IGF-1 and IGFBP-3 levels were measured using immunochemiluminometric assay and the three polymorphisms were typed for 401 Pca cases and 366 age- and ethnicity-matched controls. Multiple linear regression and multivariable unconditional logistic regression were used to test for associations between genotypes and circulating IGF levels and Pca risk, respectively. The presence of at least one copy of the IGFBP-3 -202 C allele was strongly associated with lower IGFBP-3 serum levels (3532 versus 3106 ng/ml; P = 0.008). We also observed a 2-fold increase in Pca risk for individuals homozygous for the IGFBP-3 -202 C allele [odds ratio = 2.4; 95% confidence interval = 1.2-4.8). Furthermore, IGF-1 (CA)19 genotypes were significantly associated with lower IGFBP-3 serum levels (P = 0.003). Our results reveal that variation in the 5'-untranslated region of the IGF-1 and IGFBP-3 genes may be influencing IGF serum levels and Pca risk in African-Americans and suggest a need to explore this variation across diverse populations. Our study adds clarity and further support to the previous findings, implicating serum IGFBP-3 levels and the IGFBP-3 -202 A/C SNP in prostate carcinogenesis.     

中国汉族人群前列腺癌易感性与TLR4基因单核苷酸多态性的研究

目的 探讨Asp299Gly(rs4986790)、Thr399Ile(rs4986791)、rs11536889单核苷酸多态性(SNP)与前列腺癌(PCa)易感性和严重程度的关系.方法 采用病例对照研究方法,选取组织学证据确诊的PCa患者96例为PCa组,良性前列腺增生(BPH)患者87例为BPH组,健康者92例为健康对照组.记录研究对象的临床资料并计算Gleason评分,PCR-RFLP法分析各组的基因型.结果 PCa组、BPH组及健康对照组的年龄、前列腺癌家族史所占比例、前列腺特异抗原(PSA)水平比较,差异均有统计学意义(P=0.000);PCa组、BPH组及健康对照组的Asp299Gly和Thr399Ile基因型频率分布比较,差异无统计学意义(P﹥0.05),但3组间rs11536889基因型频率分布比较,差异有统计学意义[PCa组/(BPH组+健康对照组),CC/GC vs GG,OR=2.152,95%CI:1.280~3.618,P﹤0.05];Gleason评分≥7分组GC+CC分布比例高于Gleason评分﹤7分组(OR=2.378,95%CI:1.042~4.427,P﹤0.05).结论 TLR4基因rs11536889 SNP可能与PCa发病和病情严重程度相关.