亚甲基四氢叶酸还原酶基因C677T单核苷酸多态性与卵巢癌易感性的关系

目的:研究亚甲基四氢叶酸还原酶(MTHFR)基因第4外显子677位点单核苷酸多态性与卵巢癌易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性方法,检测81例卵巢癌患者和80例正常对照者的亚甲基四氢叶酸还原酶基因C677T位点突变。结果:卵巢癌组和对照组中MTHFR基因677等位基因位点C和T的分布差异有统计学意义(P<0.05),其中等位基因T使卵巢癌发病风险增加1.93倍。MTHFR基因677C/T各基因型分布差异有统计学意义(P<0.05),纯合突变(T/T)基因型、杂合突变(C/T)基因型与野生(C/C)基因型相比,患卵巢癌的危险度分别提高了3.48倍和2.15倍。结论:MTHFR基因677位点等位基因突变与卵巢癌发生有一定关系,突变基因型增加了卵巢癌的发病风险。     

雌激素代谢酶CYP1A1及COMT基因多态性与子宫肌瘤相关性研究

目的:探讨雌激素代谢酶CYP1A1和COMT基因多态性与子宫肌瘤发生的关系。方法:应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术,对100例子宫肌瘤患者和100例对照组人群CYP1A1基因Msp I位点多态和COMT基因外显子4密码子158(G-A)多态性进行分析。结果:1两组均存在CYP1A1基因Msp I位点多态,但两组基因型TT、TC、CC频率和等位基因T、C频率的比较差异均无统计学意义(P0.05);2两组均存在COMT基因G-A多态,但两组基因型GG、GA、AA频率和等位基因G、A频率的比较差异均无统计学意义(P0.05)。结论:CYP1A1基因Msp I位点多态性和COMT基因外显子4密码子158(G-A)多态性与子宫肌瘤发病风险无相关性。     

雌激素代谢基因CYP1A2和COMT单核苷酸多态性与妊娠期肝内胆汁淤积症关系的研究

目的:探讨参与雌激素代谢的CYP1A2和COMT基因多态性与成都地区妊娠期肝内胆汁淤积症(ICP)的关系。方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,对成都地区100例ICP患者(ICP组)和100例正常孕妇(对照组)的CYP1A2基因5-'侧翼区G-2964A多态和COMT基因第4外显子第158号密码子G→A点突变所引起的缬氨酸→蛋氨酸(Val 158 Met)的错义突变多态进行分析。结果:CYP1A2 GA杂合基因型明显增加ICP的发病风险(P=0.029,OR=1.896),COMT含V等位基因的VV和VM基因型也明显增加ICP的发病风险(P=0.027,OR=3.996);两基因组合分析表明同时具有CYP1A2等位基因G和COMT等位基因V的个体发生ICP的风险显著增加(P=0.011,OR=2.852)。结论:CYP1A2和COMT基因单核苷酸多态性与成都地区ICP的易感性有关。     

CYP1A1基因多态性与宫颈鳞癌的关系

目的:检测宫颈鳞癌组织中CYP1A1等位基因的表达,探讨CYP1A1基因多态性在宫颈鳞癌发生中的作用。方法:收集宫颈鳞癌组织标本50例,以正常宫颈组织61例为阴性对照。采用等位基因特异性PCR法(ASA-PCR)和PCR扩增限制酶切法(RFLP-PCR)检测宫颈鳞癌组织中CYP1A1等位基因Exon7位点和MspⅠ位点多态性;用SPSS13.0软件建立数据库,进行χ2检验、logistic回归分析。结果:(1)CYP1A1Exon73种多态基因型在宫颈鳞癌组和对照组分布差异有统计学意义(P<0.005),宫颈鳞癌组Ile/Val、Val/Val基因型的分布频率明显高于对照组。Ile/Val和Val/Val基因型的个体发生宫颈鳞癌的OR值分别是Ile/Ile基因型个体的1.969倍和3.15倍,差异有统计学意义(P<0.05);(2)CYP1A1MspⅠ位点多态性分析:将MspⅠ位点的PCR产物行酶切分析,显示m1/m2杂合型、m2/m2突变型在宫颈鳞癌组和对照组表达差异无统计学意义(P>0.05)。结论:宫颈鳞癌组织中CYP1A1基因Exon7位点突变率升高,Ile/Val和Val/Val基因突变型个体发生宫颈鳞癌的危险性明显升高;CYP1A1基因MspⅠ位点的多态性可能与宫颈鳞癌易感性无关。     

细胞周期调控基因p21和p27单核苷酸多态性与卵巢上皮性癌的关系

目的 探讨细胞周期调控基因p21和p27的单核苷酸多态性(SNP)与卵巢上皮性癌(卵巢癌)发病风险的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测234例卵巢癌患者(卵巢癌组)和284例健康妇女(对照组)p21基因C/T和p27基因V/G SNP位点基因型和等位基因的频率分布.结果 (1)对照组妇女p21基因的C/C、C/T和T/T基因型频率分别为34.2%、49.6%和16.2%,C和T等位基因频率分别为59.0%和41.0%;卵巢癌组患者3种基因型频率分别为28.2%、53.0%和18.8%,C和T等位基因频率分别为54.7%和45.3%.两组基因型频率和等位基因频率分别比较,差异均无统计学意义(P＞0.05).3种基因型频率在4种病理类型的卵巢癌中的分布有明显差异(P=0.02),C/C基因型降低子宫内膜样癌的发病风险(OR为0.56,95%CI为0.32～0.98).(2)对照组妇女p27基因V/V、V/G和G/G基因型频率分别为88.4%、10.9%租0.7%,V和G等位基因频率分别为93.8%和6.2%;卵巢癌组患者的基因型频率分别为93.6%、5.1%和1.3%,V和G等位基因频率分别为96.2%和3.8%.两组基因型频率分布比较,差异有统计学意义(P=0.04),等位基因频率分布比较,差异则无统计学意义(P=0.09).与V/G和G/G基因型比较,V/V基因型增加卵巢癌的发病风险(OR为1.92,95%CI为1.02～3.63).结论 p21基因C/T多态性的C/C基因型可能降低子宫内膜样癌的发病风险,p27基因的V/V基因型可能是卵巢癌发病的潜在危险因素.     

CYP1A1 MspI多态性及其合并GSTM1基因缺失与子宫内膜异位症的关系

目的:探讨新疆维吾尔族、汉族人群中解毒酶细胞色素P4501A1(CYP1A1)基因MspI多态性、CYP1A1/MspI合并GSTM1基因缺失基因型与子宫内膜异位症(内异症)的关系。方法:用聚合酶链反应限制性片段长度多态性技术,检测维吾尔族107例正常妇女与41例内异症患者、汉族105例正常妇女与80例内异症患者CYP1A1基因限制性内切酶MspI位点的3种基因型的分布频率。结果:CYP1A1基因MspI位点基因型在维吾尔族正常对照组的分布频率为TT(48.6%)、TC(42.9%)、CC(8.5%),等位基因分布频率为T(70.1%)、C(29.9%),内异症组的基因型分布频率为TT(39.1%)、TC(46.3%)、CC(14.6%),等位基因分布频率为T(62.2%)、C(37.8%),差异无显著性(P>0.05);在汉族正常对照组基因型分布频率为TT(41.9%)、TC(46.7%)、CC(11.4%),等位基因分布频率为T(65.2%)、C(34.8%),内异症组基因型分布频率为TT(42.5%)、TC(51.2%)、CC(6.3%),等位基因分布频率为T(68.1%)、C(31.9%),差异无显著性。两个民族对照组之间与内异症组之间基因型频率与等位基因频率比较差异无显著性。在CYP1A1/MspI合并GSTM1(/)基因型的人群中,维吾尔族对照组与内异症组的基因型频率与等位基因频率分布比较均有显著差异(P<0.05),其TC+CC与TT比较,OR值为3.556(P<0.05)。汉族对照组与内异症组的比较无统计学差异。结论:解毒酶CYP1A1基因MspI多态性本身可能与维吾尔族及汉族内异症发病无关,而CYP1A1/MspI合并GSTM1(/)基因型可能与维吾尔族内异症发病有关。     

CYP1A1基因多态性与子宫内膜腺癌发生的关系研究

目的研究细胞色素P4501A1(CYP1A1)基因MspI位点和Ile-Val位点多态性与子宫内膜腺癌发生的关系。方法以病例-对照研究,采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)方法和等位基因特异性PCR(AS-PCR)技术检测84例子宫内膜腺癌患者和66例对照者CYP1A1基因MspI位点和Ile-Val位点的多态性。结果Ile-Val三种多态基因型在对照组和子宫内膜腺癌组中的分布在显著性差异(P<0.05),其中Ile/Val和Val/Val基因型在子宫内膜腺癌组中的分布频率明显高于对照组。与Ile/Ile基因型相比,Ile/Val基因型个体发生子宫内膜腺癌的相对危险度(OR)是2.682,两者差异有统计学意义(P<0.05);而MspI位点的多态性在对照组和子宫内膜腺癌组中的分布差异无统计学意义(P>0.05)。结论CYP1A1基因第7外显子的Ile/Val基因型与子宫内膜腺癌的发生有关,可以作为子宫内膜腺癌易感人群筛查的重要指标,MspI位点多态性与子宫内膜腺癌的发生无相关性。     

CYP1A1基因多态性与子宫内膜癌易感性关系的研究

目的:研究细胞色素P4501A1(CYP1A1)基因MspⅠ位点多态性与子宫内膜癌发生的关系。方法:用PCR-RFLP法检测174例子宫内膜腺癌患者和114例对照者CYP1A1基因MspI位点多态性。结果:合并杂合型T/C和突变型C/C后与野生型T/T比较,两组差异有统计学意义(P=0.047,OR=1.635)。在绝经年龄<50岁的病例组,T和C等位基因频率与对照组相比差异有统计学意义(P=0.032);初潮年龄≤14岁,等位基因频率在两组中差异有统计学意义(P=0.036);经BMI分层分析,未发现MspI多态性与子宫内膜癌有关。结论:CYP1A1基因MspI多态中突变等位基因C可显著增加子宫内膜癌的发病风险,且绝经年龄越早、初潮年龄越早携带等位基因C的个体越易感子宫内膜癌。     

XPC基因多态性与卵巢上皮性癌易感性的关系

目的 核苷酸切除修复基因XPC(着色性干皮病基因组C)与多种肿瘤的发病相关,通过检测第9内含子PAT-/+和第15外显子A/C单核苷酸多态性(SNP)探讨其与卵巢上皮性癌易感性的关系.方法 选取2001年12月至2005年11月在河北医科大学第四医院卵巢上皮性癌患者208例和正常对照者231例.采用聚合酶链反应-限制性片段长度多态性方法检测XPC的多态性基因型.结果 XPC基因第9内含子PAT-/+SNP,第15外显子A/C SNP卵巢癌组及对照组的基因型频率分布,等位基因频率两组比较无统计学意义(P＞0.05).以-/-、A/A基因型做参照,与其它两型比较均不能增加卵巢癌的发病风险.将卵巢癌组病理类型分组,分别与正常对照组相比及在各病理类型之间相比较,基因型频率分布无统计学意义(P＞0.05).早期(Ⅰ、Ⅱ期)卵巢癌与晚期(Ⅲ、Ⅳ期)卵巢癌的基因型频率分布无统计学意义(P＞0.05).结论 研究未发现XPC基因第9内含子PAT-/+及第15外显子A/C多态与卵巢癌的易感性相关.     

人CYP17基因启动子5'上游-34碱基处T→C突变与复发性流产

目的:探讨人类CYP17基因启动子5'上游-34碱基处T→C突变与复发性流产的关系,以期为预防和治疗该病易感人群提供新思路。方法:采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法,针对CYP17基因启动子5'上游-34碱基处的多态性,检测96例患有原因不明复发性流产患者(病例组)和102例有生育史的健康女性(对照组),并用非变性聚丙烯酰胺凝胶电泳和银染法进一步验证,且采用测序方法证实实验结果。结果:病例组和对照组CYP17基因启动子5'上游-34碱基处T和C的分布差异有统计学意义(χ2=8.188,P0.05),CYP17基因各基因型分布差异有统计学意义(χ2=10.096,P0.05)。杂合突变(T/C)基因型和纯合突变(C/C)基因型患复发性流产的危险度较野生(T/T)基因型分别提高了0.424和0.271倍。结论:人CYP17基因启动子5'上游-34碱基处T→C突变与中国东北地区人群复发性流产有关,C等位基因可能是复发性流产的遗传易感因素之一。     

Association of CYP1B1 gene polymorphisms and the positive expression of estrogen alpha and estrogen beta with endometrial cancer risk

To investigate the relationship between the CYP1B1 L432V polymorphism, ERalpha and ERbeta positivities and the incidence of endometrial cancer. The relationship between CYP1B1 L432V polymorphism, ERalpha and ERbeta positivities and endometrial cancer was investigated using the allele-specific polymerase chain reaction method to analyze gene polymorphism in exon 3 codon 432 (C-G) of CYP1B1. Our results are as follows: in endometrial cancer cases the prevalence rates of CYP1B1 L432V genotypes C/C, C/G, and G/G were 47.2%, 36.1%, and 16.7%, respectively, and 68.8%, 23.8% and 7.5% in the control group, respectively. The frequencies of CYP1B1 C and G alleles were 65.3% and 34.7% in endometrial cancer patients and 80.6% and 19.4% in the control group. A significant difference was found in the genotype distributions or allele frequencies of CYP1B1 L432V polymorphism between the two groups (p < 0.05). Compared with wild-type C/C, the susceptibility of endometrial cancer with homozygotic mutation G/G and heterozygotic mutation C/G increased by 3.235 (95%CI 1.111-9.425) and 2.214 (95% CI 1.067-4.593). Moveover, the positive expression of ERalpha in genotypes G/G and C/G was higher than in the wild genotype C/C (p < 0.05). In conclusion, allelic polymorphism of CYP1B1 L432V increases the risk of endometrial cancer and has a positive correlation with ERalpha expression.     

CYP1A1 and CYP1B1 genetic polymorphisms and uterine leiomyoma risk in Chinese women

Purpose  The aim of the study was to evaluate the association of CYP1A1 and CYP1B1 polymorphisms with uterine leiomyoma in Chinese women. Methods  We investigated 100 women with clinically diagnosed uterine leiomyoma and 110 healthy normal subjects from Chinese women. The genetic distribution of two CYP1A1 polymorphisms at MspI, Ile462Val and four CYP1B1 polymorphisms at Arg48Gly, Ala119Ser, Leu432Val, Asp449Asp were analyzed by polymerase chain reaction–restriction fragment length polymorphism and DNA sequencing method. Results  All the SNPs showed polymorphisms in Chinese women. The genotype A/G and the allele G on Ile462Val was significantly different between uterine leiomyoma patients and controls (P < 0.05). Conclusion  These results suggest that the genotype of CYP1A1 Ile462Val was associated with the increased risk of uterine leiomyomas in Chinese women. Capsule This is the first report that demonstrates the polymorphism at Ile462Val of CYP1A1 to be associated with uterine leiomyoma in Chinese women.     

Single nucleotide polymorphisms and haplotypes of the genes encoding the <Emphasis Type="Italic">CYP1B1</Emphasis> in Korean women: No association with advanced endometriosis

Objective: To investigate whether single nucleotide polymorphisms and its haplotypes of gene encoding CYP1B1 are associated with the risk of advanced endometriosis in Korean women. Methods: We investigated 221 patients with histopathologically confirmed endometriosis rAFS stage III/IV and 188 control group women who were surgically proven to have no endometriosis. The genetic distribution of four different CYP1B1 polymorphisms at Ala119Ser, Leu432Val, Asp⁴⁴⁹(C>T), Asn453Ser were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism of PCR products. Haplotype analysis was also performed. Results: We found no overall association between each individual CYP1B1 genotype or haplotype and the risk of endometriosis. Also, the odds ratio of each haplotypes of CYP1B1 showed no association with the risk of endometriosis. Conclusions: These results suggest that CYP1B1 genetic polymorphism may not be associated with development of advanced endometriosis in Korean women. CYP1B1 genetic polymorphism may not be associated with development of advanced endometriosis.     

Polymorphisms in the promoter regions of the matrix metalloproteinases-1, -3, -7, and -9 and the risk of epithelial ovarian cancer in China

PURPOSE: To investigate the association of single nucleotide polymorphisms (SNP) in the promoter region of the matrix metalloproteinases-1 -1607bp1G/2G, matrix metalloproteinases-3 -1171bp5A/6A, matrix metalloproteinases-7 A-181G and matrix metalloproteinases-9 C-1562T with susceptibility to ovarian cancer in a population of North China. EXPERIMENTAL DESIGN: We analyzed four different functional promoter polymorphisms in the respective genes by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in a sample of patients with epithelium ovarian cancer and control women, all from North China. RESULTS: No significant difference was detected between the patient and control groups in genotype and allelotype distribution of MMP-1, MMP-3, MMP-9 of the polymorphisms studied. However, the genotype and allelotype of the MMP-7 distribution in ovarian cancer patients were significantly different from that in healthy controls. The frequency of the -181G allele of MMP-7 in patients was significantly higher than that in healthy controls women (8.2% vs. 2.8%, P = 0.002). Compared to the A/A genotype, the genotypes with the -181G allele (A/G + G/G) significantly increased susceptibility to ovarian cancer, with adjusted odds ratio [OR] = 3.53 95% confidence interval [CI] [1.58 to 7.89]. CONCLUSIONS: The study suggested that a possible association between the MMP-7 A/G polymorphism with susceptibility to epithelium ovarian cancer, but there is no support for an association of the selected MMP-1 1G/2G, MMP-3 5A/6A, and MMP-9 C/T polymorphisms with the risk for ovarian cancer.     

Germline mutations of BRCA1 and BRCA2 in Korean sporadic ovarian carcinoma

OBJECTIVES: Mutations in the BRCA1 and BRCA2 genes predispose women to ovarian and/or breast cancer. The contribution of BRCA1 and BRCA2 mutations to ovarian cancer in Korean women remains to be elucidated. In addition, genetic polymorphisms may affect not only cancer development but also cancer progression and, as a result, could influence cancer phenotypes. The purposes of this study were, first, to investigate the presence of BRCA1 and BRCA2 mutations in women with ovarian cancer who were unselected for family history and, second, to evaluate the relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features. METHODS: We studied 37 women who were diagnosed with epithelial ovarian cancer and treated at the Yonsei University Hospital between August 2002 and March 2004. Genomic DNA was analyzed for BRCA mutations using a PCR-DHPLC-sequencing method. The relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features was examined. RESULTS: Most mutations of BRCA1 and BRCA2 associated with ovarian and/or breast cancer result in truncated proteins. We found one frameshift mutation in BRCA1 (3746insA) that led to premature termination. The patient had no family history of breast or ovarian cancer. There was no relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features. CONCLUSION: Our results were consistent with the hypothesis that BRCA1 and BRCA2 mutations have a limited role in sporadic ovarian carcinogenesis in the Korean population. Furthermore, polymorphisms of certain, selected ovarian cancer susceptibility genes were not associated with the clinicopathological phenotypes of ovarian cancer.     

Polymorphisms of the interleukin-1 gene cluster and ovarian cancer

OBJECTIVE: Interleukin-1 (IL-1) is known to be critically involved in ovarian carcinogenesis. We investigated a panel of polymorphisms of the IL-1 and the IL-1 receptor antagonist (IL-1 RA) genes in patients with ovarian cancer. METHODS: One hundred thirty-four patients with surgically staged ovarian cancer, 27 patients with borderline ovarian cancer, and 134 healthy controls were genotyped for three polymorphisms of the IL-1 gene (-889 C/T polymorphism of the IL-1alpha gene [IL1A], -511 C/T polymorphism of the IL-1beta promoter [IL1B promoter], a polymorphism of IL-1beta exon 5 [IL1B exon 5]), and an 86-base pair repeat in intron 2 of the IL-1 RA gene [IL1RN]) using polymerase chain reaction and pyrosequencing. RESULTS: Allelic frequencies did not differ between patients with ovarian cancer and controls. In the ovarian cancer group, polymorphism did not correlate with any of the investigated clinicopathologic variables, including tumor stage, lymph node, and histologic grade. In univariate and multivariate models, there was no correlation between any polymorphism and patients' overall and disease-free survival. CONCLUSION: We investigated interleukin polymorphisms in ovarian cancer but did not find any association between common polymorphisms of IL1A, IL1B, and IL1RN and the occurrence of ovarian cancer. Allelic variation within the IL-1 gene clusters does not seem to play a role in ovarian carcinogenesis and does not appear to be a useful tool for possible screening and risk evaluation.