10个雌激素相关基因的多态性与子宫内膜异位症:关于多个基因间相互作用的研究

Objective: Genetic as well as hormonal factors are known to influence the development and clinical course of endometriosis. We aimed to investigate the association among 10 single nucleotide polymorphisms (SNPs) involved in the estrogen metabolism and endometriosis and to develop a multiple genetic model. METHODS: In a case-control study, we investigated the genotype frequencies of 10 estrogen metabolizing SNPs in 32 patients with endometriosis and 790 healthy controls using sequencing-on-chip-technology with solid-phase polymerase chain reaction on oligonucleotide microarrays: catechol-O-methy-ltransferase, Val158Met G->A, 17-β-hydroxysteroid dehydrogenase type 1 (HSD17), vIV A->C, cytochrome P450 (CYP), 17 A2 allele T->C, CYP1A1 Mspl RFLP T->C, CYP1A1 Ile462ValA->G, CYP19 Arg264-Cys C->T, CYP19 C1558T C->T, CYP 1B1 Leu432Val, CYP1B1 Asn453Ser, and estrogen receptor alpha. IVS1-401>C. Associations and 2-way interaction models between SNPs were calculated by stepwise logistic regression models. RESULTS: In a univariate model, HSD17 vIV A->C was associated with a significantly increased risk of endometriosis (P = .004; odds ratio 3.9, 95%confidence interval 1.6-9.8). When all 2-way interactions of investigated SNPs were ascertained, no significant interactions among SNPs were observed. In a multivariate model, HSD17 vIV A->C was also significantly associated with endometriosis (P = .002). CONCLUSION: We present data on multiple SNPs in patients with endometriosis indicating an association between HSD17 gene variation and the disease. Although not able to demonstrate interaction models of SNPs, we provide evidence of HSD17 vIV A->C as a low penetrance genetic marker of endometriosis.

血清中鳞状上皮细胞癌抗原水平对早期外阴癌的预测价值

Objective. To determine whether SCC- Ag serum levels can be used as a prognostic parameter in surgically treated early stage vulvar cancer. Methods. SCC- Ag serum levels were measured preoperatively in 61 surgically staged patients with squamous cell vulvar cancer (UICC pT1 and pT2). Results were correlated to clinical data. Results. Mean (standard deviation) SCC- Ag serum levels in patients with vulvar cancer were 1.5 (1.99) ng/mL. SCC- Ag serum levels were significantly higher in patients with pT2 vulvar cancer (2.2 [2.6] ng/mL) compared with patients with pT1 vulvar cancer (1.0 [1.2] ng/mL, P = 0.034). SCC- Ag serum levels were not associated with lymph node involvement (P = 0.1), tumor grade (P = 0.6), and patients’ age (P = 0.5). Multivariate Cox regression models considering tumor stage, lymph node involvement, patients’ age, and SCC- Ag serum levels as covariates showed that lymph node involvement (P = 0.04 and P = 0.01) and tumor stage (P = 0.006 and P = 0.009), but not SCC- Ag serum levels (P = 0.8 and P = 0.6), and patients’ age (P = 0.08 and P = 0.22) are prognostic factors for disease-free and overall survival, respectively. Conclusion. SCC- Ag serum levels cannot be used as an additional prognostic parameter in patients with surgically treated early stage vulvar cancer.

单核苷酸多态性DNA微矩阵分析有利于评估激素治疗的利弊

Objective To determine what percentage of women can be given individu alized co unseling based on genetic information, as single nucleotide polymorphisms (SNPs) are associated with risks and benefits of estrogen therapy and hormone therapy such as thrombosis, myocardial infarction, breast cancer, and bone protection. D esign Cross-sectional study. Setting Academic research institution. Patient(s) A consecutive series of 2,507 perimenopausal and postmenopausal women. Intervent ion(s) Peripheral venous puncture and multiplex polymerase chain reaction on a m icroarray system. Main outcome measure(s) Analysis of 22 SNPs of 17 genes: AGTMe t235Thr, APOECys112Arg, APOEArg158-Cys, COMTVal158Met, CYP17-34T >C, CYP191558 C >T, CYP19Arg264Cys, CYP1A16235T >C, CYP1A1Ile462Val, CYP1B1Leu432Val, CYP1B1A -sn453Ser, HSD17B1-27A >C, ER-αIVS-401T >C, prothrombin20210G >A, factor V Leiden, eNOS-786T >C, eNOSGlu298Asp, MRSer810L eu, MTHFR677C >T, PAI 15G >4G, SRD5A2Val89Leu, and VDRb >B. Result(s) Among the women in the study, 66%had at least two homozygous mutant SNPs of interest. A t hrombophilic disposition was found in 9.9%of women, and 23%of women had at lea st two SNPs associated with an increased risk of breast cancer (COMT, CYP17, CYP 19, CYP1A1, and CYP1B1). The SNPs predisposing women to cardiovascular pathologi es (e.g., APOE, AGT, eNOS, and PAI 1) were found in 12.3%of women. Carriage of SNPs predisposing to early postmenopausal bone loss and osteoporosis (ER-αand VDR) were found in 26.7%of women. Conclusion( s) These data suggest that the as sessment of SNPs associated with risks and benefits of estrogen/hormone therapy may be a new means to individualize counseling about and prescription of estroge n/hormone therapy in up to 66%of women.

一种预测白种女性绝经期年龄的模型

Objective: To develop a model to predict the age at natural menopause and the risk for premenopausal hysterectomy. Design: Cross- sectional study. Setting: Multicenter study. Patient(s): A total of 1,345 white women. Intervention(s): Ten single nucleotide polymorphisms (SNPs) of seven estrogen (E)- metabolizing genes (i.e., catechol- O- methylt- cytochrome P- 450 [CYP] 17, CYP1A1, CYP1B1, CYP19, and E receptor [ER]- α ) were analyzed by sequencing- on- chip- technology. Main Outcome Measure(s): Patients’ reproductive and medical histories were ascertained and correlated to genotypes. Result(s): The model incorporates the number of full term pregnancies, the body mass index (BMI), a history of breast surgery, and the presence of CYP17 and CYP1B1- 4 polymorphisms as well as the BMI to predict age at natural menopause and the risk for undergoing premenopausal hysterectomy. Conclusion(s): We present the first model to date, which can predict age at natural menopause and the risk for undergoing premenopausal hysterectomy based on genotype information and personal history.

芳香化酶抑制剂阿纳托唑阴道给药治疗直肠阴道子宫内膜异位症的初步研究

In the present nonrandomized pilot study we determined the role of the vaginally administered aromatase inhibitor anastrozole (0.25 mg anastrozole/d for 6 months) in the treatment of women with histologically proven rectovaginal endometriosis. In a series of 10 patients, dysmenorrhea, physical and social functioning, but not chronic pelvic pain and dyspareunia, improved during therapy.