CYP1A1 gene polymorphism and polycystic ovary syndrome

The aim of this study was to assess the rates of variant alleles of cytochrome P4501A1 (CYP1A1) in patients with polycystic ovary syndrome (PCOS). It was designed as a case-control study in Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology and Genetics. Forty-eight patients with PCOS served as the study group. Ninety-six regularly cycling women with no clinical and biochemical evidence of hyperandrogenism and polycystic ovary appearance served as the controls. The CYP1A1 variant alleles of all patients were determined via polymerase chain reaction. The rate of the CYP1A1 isoleucine (Ile)/valine (Val) allele was significantly higher in patients with PCOS than in the controls (OR: 7.8, 95% CI: 3.45-17.52, P < 0.001). However, there was no statistically significant difference in the distribution of Val/Val genotype (OR: 4.0, 95% CI: 0.60-26.73). The rate of any Val genotype (Ile/Val or Val/Val) was significantly higher in patients with PCOS compared with the control group (OR: 7.4, 95% CI: 3.33-16.46, P < 0.001). In conclusion, the patients with PCOS had a 7.8-fold higher frequency of CYP1A1 Ile/Val genotype and a 7.4-fold higher frequency of CYP1A1 of any Val genotype (Ile/Val or Val/Val).     

CYP1A1 gene polymorphism as a risk factor for cervical intraepithelial neoplasia and invasive cervical cancer

OBJECTIVE: The purpose of this study was to evaluate the role of CYP1A1*3 gene polymorphism in the development of cervical cancer by comparing patients having cervical intraepithelial neoplasia (CIN) or invasive cervical cancer with control subjects. METHODS: CYP1A1*3 polymorphism was analyzed using an allele-specific PCR-based method. RESULTS: In the group of patients with CIN, the frequency of the Ile/Val and of any Val alleles was significantly higher than in the healthy control subjects (OR: 4.51; 95%CI = 2.42-8.43, and OR: 3.71; 95%CI = 2.03-6.78). In the CIN1 group, patients with Ile/Val and any Val genotypes were found to be significantly higher (OR: 10.53; 95%CI = 3.78-29.33 and OR: 8.38; 95%CI = 3.04-23.08). In the CIN2 group, patients with Ile/Val and any Val revealed a 4.06- and 3.23-fold higher risk than those with Ile/Ile (95%CI = 1.54-10.74 and 1.24-8.45). However, the variance in the group of patients with CIN3 did not reach statistical significance. Patients with cervical cancer were analyzed with respect to the histological diagnoses. In the adenocancer group, the estimated ORs with respect to the control subjects were 11.29 for Ile/Val (95%CI = 3.35-38.07) and 8.98 for any Val groups (95%CI = 2.69-30.01), with a statistical significance. Among the squamous cell cancer patients, Ile/Val and any Val were significantly higher than in controls (OR: 5.76; 95%CI = 3.13-10.59 and OR: 5.20; 95%CI = 2.91-9.28). Although Val/Val genotype did not reach a significant value, it was near significance with an OR of 3.03 (95%CI = 0.95-9.68). CONCLUSION: These results suggest that CYP1A1*3 gene polymorphism is linked to a propensity for cervical carcinogenesis and further series are needed to detect the exact role of this unique variation.     

CYP1A1 gene polymorphism and risk of endometrial hyperplasia and endometrial carcinoma

The cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental carcinogens and estrogen. We hypothesized that CYP1A1 genetic polymorphism may be a susceptibility factor for endometrial hyperplasia (EH) and endometrial carcinoma (ECa). We therefore evaluated this hypothesis in patients with EH and ECa and control subjects using allele-specific polymerase chain reaction-based method in a Turkish population. The patients with CYP1A1 Ile/Val genotype had a fivefold higher risk of having EH than those with Ile/Ile. In contrast, a higher frequency of any Val genotype (Ile/Val and Val/Val) was found in patients with EH, indicating that persons carrying any Val allele are at increased risk for developing EH. In the ECa group, patients were also more likely to have CYP1A1 Ile/Val allele, with an adjusted odds ratio of 3.0. Moreover, there was a statistically significant increase in relative risk association with any Val genotype between patients and controls, suggesting that individuals carrying any Val genotype are at increased risk for developing ECa. We concluded that variant alleles of the CYP1A1 gene might be associated with EH and ECa susceptibility. Further studies with a large sample size should be considered to address issues of interactions between CYP1A1 and other risk factors.     

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。     

CYP1A1 polymorphism in adolescents with polycystic ovary syndrome

Objective

To evaluate the rates of the CYP1A1 Ile/Val polymorphism in Turkish adolescent females.

Methods

The CYP1A1 Ile/Val polymorphism was analyzed by collecting DNA samples from 44 adolescents with polycystic ovary syndrome (PCOS)—according to the Rotterdam criteria—and 120 healthy female controls aged 13-18 years in Ankara, Turkey.

Results

There was a 2.5-fold increase in the frequency of the CYP1A1 Ile/Val genotype in adolescents with PCOS compared with the control group (odds ratio [OR] 2.54; 95% confidence interval [CI], 1.143-5.637; P < 0.001), in addition to a 2.4-fold increase in the frequency of the Val allele (OR 2.43; 95% CI, 1.099-5.397; P < 0.001).

Conclusion

The data show an association between CYP1A1 and PCOS, indicating that variant alleles of the gene may affect the metabolic and transport pathway of estrogens, thus causing PCOS.     

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 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.     

Association of XRCC1 Arg399Gln and OGG1 Ser326Cys polymorphisms with the risk of cervical cancer in Japanese subjects

OBJECTIVE: In this study, genetic polymorphisms, XRCC1 Arg399Gln and OGG1 Ser326Cys were examined with reference to cervical cancer risk in a population-based incident case-control study in Japan. METHODS: The cases comprised 131 cervical cancer patients: 87 cases with squamous cell carcinoma (SCC) and 44 with adenocarcinoma (ADC) or adenosquamous carcinoma (ADSC). Controls were sampled from 320 healthy women who underwent a health checkup. RESULTS: The frequency of the XRCC1 399GlnGln genotype was higher in individuals with adenocarcinoma/adenosquamous carcinoma than in the healthy controls (OR = 2.98, 95% CI = 1.11-8.01, P = 0.030). However, no association was demonstrated in SCC. Analysis of OGG1 Ser326Cys polymorphism showed no significant differences between cervical cancer patients and controls. In stratification analysis, significant elevated risk of adenocarcinoma/adenosquamous carcinoma was associated with the XRCC1 399GlnGln genotype among nonsmokers (OR = 3.85, 95% CI = 1.28-11.59, P = 0.017), but not among smokers. No gene-gene interaction was observed in our case subjects. CONCLUSION: This is the first report that the XRCC1 Arg399Gln polymorphism might be important in relation to the risk of adenocarcinoma/adenosquamous carcinoma of the cervix.     

儿茶酚-O-甲基转移酶基因多态性与子宫内膜癌遗传易感性的关系

目的探讨儿茶酚-O-甲基转移酶（COMT）基因多态性与子宫内膜癌遗传易感性的关系。方法以聚合酶链反应-限制性片段长度多态性（PER-RFLP）方法,对132例子宫内膜癌患者（内膜癌组）和110例子宫脱垂、宫颈鳞癌和卵巢良性囊肿患者（对照组）的COMT基因第4号外显子第158位密码子G与A的多态性进行分析,用非条件logistic回归分析COMT基因多态性与子宫内膜癌发生风险的关系。结果对照组患者以COMT灿蹦基因型为主（47．2％,52／110）,COMT^Val/Met（45．5％,50／110）和COMT^Met/Met（7．3％,8／110）次之;内膜癌组则以COMT^Val/Met基因型为主（58．3％,77／132）,COMT^Val/Val（29．5％,39／132）和COMT^Met/Met（12．1％,16／132）次之,两组比较,差异有统计学意义（P〈0．05）。经非条件logistic回归分析,与COMT^Met/^Met基因型相比,COMT^Val/Val基因型者的子宫内膜癌发生风险的OR值为0．262（95％（7／为0．080～0．862,P=0．027）。结论中国南方汉族妇女的COMT基因型以COMT^Val/Val最多,携带COMT^Val/Val基因型的妇女相对于COMT^Met/^Met基因型者,其发生子宫内膜癌的风险可能降低。     

Perineal talc exposure and subsequent epithelial ovarian cancer: a case-control study

OBJECTIVE: To evaluate the role of talcum powder use as a risk factor for the development of epithelial ovarian cancer. METHODS: In a case-control study, 499 patients with epithelial ovarian cancer were frequency matched for age at diagnosis (-5 years) with a control population of 755 patients. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, education, geographic location, history of tubal ligation, and previous hysterectomy. RESULTS: Two hundred twenty-one of 462 patients (47.8%) in the study population and 311 of 693 patients (44.9%) in the control population had ever used talcum powder (OR 0.92; 95% confidence interval [CI] 0.24, 3.62). A significant association between duration of talc use and development of epithelial ovarian cancer was not demonstrable for 1-9 years (OR 0.9; 95% CI 0.6, 1.5), for 10-19 years (OR 1.4; 95% CI 0.9, 2.2), or for more than 20 years (OR 0.9; 95% CI 0.6, 1.2). To eliminate the possible confounding variable of surgery for the management of ovarian cancer, we omitted 135 patients in the study population who underwent hysterectomy within 5 years of the diagnosis of ovarian cancer. Within this subgroup of patients, tubal ligation or hysterectomy among talc users still failed to demonstrate an increased risk for the development of ovarian cancer (OR 0.9; 95% CI 0.4, 2.2). CONCLUSION: A significant association between the use of talcum powder and the risk of developing epithelial ovarian cancer is not demonstrable, even with prolonged exposure.     

Interleukin 1 beta gene polymorphism and risk of cervical cancer.

OBJECTIVE: To determine whether a polymorphism at position +3953 in exon 5 of the lL-1beta gene (IL-1beta +3953), a condition associated with an increased risk for a number of inflammatory diseases, is also involved in the development of cervical cancer. METHOD: We isolated DNA from peripheral blood in 150 women with cervical cancer and 200 healthy controls, and IL-1beta +3953 allele polymorphism was determined by polymerase chain reaction. RESULTS: Genotypes A1/A2 and A2/A2+A1/A2 were associated with increased risk of cervical cancer (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.78-4.67; P<0.001 and OR, 2.85; 95% CI, 1.77-4.6; P<0.001, respectively). The risk in a passive smoker with A2/A2 or A1/A2 genotype was increased more than 5-fold (OR, 5.69; 95% CI, 2.61-12.50; P<0.001) compared with a nonsmoker with the A1/A1 genotype. CONCLUSION: This study provides evidence of an association between lL-1beta +3953 polymorphism and risk of cervical cancer.     

Polymorphism and overexpression of HER2/neu among ovarian carcinoma women from Tiruchirapalli, Tamil Nadu, India

Purpose

Alteration and overexpression of HER2 proto-oncogene have been implicated in the carcinogenesis and prognosis of ovarian cancer. We evaluated this hypothesis among women with ovarian carcinoma patients from Tiruchirapalli, Tamil Nadu, India.

Methods

Genomic DNA was extracted from 72 case patients and 288 control subjects and was examined for I655V polymorphism by PCR–RFLP based assay. Immunohistochemistry analysis was carried out in order to study the overexpression of HER2 protein. The observed number of each genotype was compared with that expected for a population in the Hardy–Weinberg equilibrium. In analysing the relation between genotype and overexpression of HER2 protein, Cochran-Mantel–Haenszel statistics was used.

Results

We found that 20.8 % of the case patients and 16.3 % of the control subjects were heterozygous for the Val allele and 10 case patients (13.8 %) and 3 control subjects (1.1 %) were homozygous for this allele (P < 0.001). Compared with women with Ile/Ile genotype, women with Val/Val genotype had an elevated risk of ovarian cancer. The genotype distributions were consistent with the Hardy–Weinberg equilibrium. The risk increased with the number of Val allele and women homozygous for the Val allele had 15-fold (OR = 15.3; 95 %CI = 4.09–57.31) increased risk of cancer. The patients homozygous for the Valine allele showed strong HER2 protein expression.

Conclusion

The results showed that the valine allele may be an indicator of genetic susceptibility to ovarian carcinoma in the study population.     

Fas gene promoter –670 polymorphism in gynecological cancer

Abstract.   Ueda M, Terai Y, Kanda K, Kanemura M, Takehara M, Yamaguchi H, Nishiyama K, Yasuda M, Ueki M. Fas gene promoter −670 polymorphism in gynecological cancer. Int J Gynecol Cancer 2006; 16(Suppl. 1): 179–182.
Single-nucleotide polymorphism at −670 of Fas gene promoter (A/G) was examined in a total of 354 blood samples from normal healthy women and gynecological cancer patients. They consisted of 95 normal, 83 cervical, 108 endometrial, and 68 ovarian cancer cases. Eighty-three patients with cervical cancer had statistically higher frequency of GG genotype and G allele than 95 controls ( P = 0.0353 and 0.0278, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and endometrial or ovarian cancer patients. The Fas −670 GG genotype was associated with an increased risk for the development of cervical cancer (OR = 2.56, 95% CI = 1.08–6.10) compared with the AA genotype. The G allele also increased the risk of cervical cancer (OR = 1.60, 95% CI = 1.05–2.43) compared with the A allele. Germ-line polymorphism of Fas gene promoter −670 may be associated with the risk of cervical cancer in a Japanese population.     

UGT1A1基因启动子多态性与伊立替康化疗毒性作用的关系

目的 初步了解宫颈癌和卵巢癌患者血中尿苷二磷酸葡萄糖醛酸转移酶1A1( UGT1 A1)基因启动子的多态性情况,并研究其多态性与伊立替康化疗的毒性作用(延迟性腹泻、中性粒细胞减少)的关系.方法 收集64例使用伊立替康联合顺铂方案化疗的宫颈癌和卵巢癌患者的全血标本,提取基因组DNA,PCR扩增UGT1A1基因启动子,用毛细管电泳等位基因片段分析方法分析UGT1A1基因启动子的多态性,并与化疗毒性作用进行相关性分析.结果 64例患者中UGT1 A1基因启动子的野生纯合型(TA 6/6基因型)最为常见,共44例,占69％ (44/64);其次为突变杂合型(TA 6/7基因型),共17例,占27％ (17/64);突变纯合型(TA 7/7基因型)仅3例,占5％(3/64).UGT1A1基因启动子基因型是发生延迟性腹泻的独立影响因素(OR=4.228,95％ CI为1.065～16.785,P=0.040),但不是中性粒细胞减少发生的独立影响因素(OR=3.659,95％ CI为0.911～14.700,P=0.068);TA 6/7和TA 7/7基因型比TA 6/6基因型患者发生中性粒细胞减少、延迟性腹泻的风险高(P均=0.001).结论 在宫颈癌、卵巢癌患者中,UGT1 A1基因启动子以TA 6/6基因型较常见.UGT1A1基因启动子多态性是伊立替康所致延迟性腹泻的独立影响因素,TA 6/7和TA 7/7基因型患者发生延迟性腹泻的风险高于TA 6/6基因型.     

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.     

Cyclin D1 polymorphism and the risk of endometrial cancer

OBJECTIVES: The common G to A single nucleotide polymorphism (G870A) in the splice donor region of exon 4 enhances alternate splicing, and produces a longer half-life cyclin D1 (CCND1). This study was aimed at investigating the possible association between the G870A polymorphism in CCND1 and the risk of endometrial cancer. METHODS: We assessed the association between the CCND1 G870A polymorphism and the risk of endometrial cancer in a hospital-based case-control study among 231 Korean women (77 cases; 154 matched controls). Controls were matched to cases with respect to age, menopausal status, and hormone therapy status. RESULT: The allele frequencies of the case subjects (A, 0.45; G, 0.55) were significantly different from those of control subjects (A, 0.58; G, 0.42) (P = 0.008). All case and control subjects were in Hardy-Weinberg equilibrium. The AA genotype was associated with a significantly elevated odds ratio (OR) of 3.18 [95% confidence interval (CI) 1.38-7.37, P = 0.007], and the AG genotype was associated with an OR of 1.38 (95% CI 0.65-2.89). When we combined the GG and AG genotypes as a reference genotype, we found that the OR for the AA genotype was 2.53 (95% CI 1.34-4.80, P = 0.004), supporting a recessive model for the A allele. Conditional logistic regression adjusted for various risk factors of endometrial cancer revealed positive associations between the AA genotype and an increased risk of endometrial cancer (OR 3.16, 95% CI 1.18-8.43, P = 0.022). However, no significant difference in endometrial cancer stage or grade was observed between the CCND1 genotypes. CONCLUSION: Our data suggest that the CCND1 polymorphism is associated with an increased risk of endometrial cancer. To validate this association, a large-scale population-based study is needed.     

Reproductive and dietary risk factors for epithelial ovarian cancer in China

OBJECTIVE: A case-control study was conducted to investigate the effects of reproductive and dietary risk factors on ovarian cancer risk in China. METHODS: Cases were 254 patients with histologically confirmed epithelial ovarian cancer. Controls were 652 women without neoplasm and long-term dietary modifications. Information was collected using a structured questionnaire on sociodemographic and reproductive characteristics, diet, medical and family cancer history. The risks of ovarian cancer were assessed by multivariate logistic regression analysis. RESULTS: The adjusted odds ratios (OR) for women having at least two full-term pregnancies, two or more incomplete pregnancies, and first full-term pregnancy at 21-25 years of age were 0.45 (95% CI 0.3-0.8), 0.56 (95% CI 0.4-0.8), and 0.40 (95% CI 0.2-0.8), respectively, compared with nulliparity. The OR of ever lactation was 0.50 (95% CI 0.3-0.8) and oral contraceptive was 0.48 (95% CI 0.3-0.7), while postmenopausal women appeared to have an increased risk with OR 1.48 (95% CI 1.0-2.3). For the highest versus the lowest quartile intakes of nutrients, the OR were 2.17 (95% CI 1.3-3.8) for fat, 0.36 (95% CI 0.2-0.6) for fibre, 0.26 (95% CI 0.2-0.5) for carotene, 1.59 (95% CI 0.9-2.7) for retinol, 0.31 (95% CI 0.2-0.5) for vitamin C, and 0.41 (95% CI 0.2-0.7) for vitamin E, with significant dose-response relationships. CONCLUSION: It is evident that full-term and incomplete pregnancies, lactation, and oral contraceptive use can reduce the ovarian cancer risk. Moreover, consumption of foods low in fat but high in fibre, carotene and vitamins appears to be protective against ovarian cancer in Chinese women.     

基质金属蛋白酶1、3基因多态性与卵巢癌遗传易感性关系的研究

目的 探讨基质金属蛋白酶(MMP)1、3基因启动子区多态性与卵巢癌遗传易感性的关系。方法 采用限制性片段长度多态性聚合酶链反应(PCR—RFLP)分析122例上皮性卵巢癌患(卵巢癌组)和151例同一地区的健康汉族妇女(对照组)MMP-1和MMP-3的基因型。结果 卵巢癌组MMP-1的2G和1G等位基因频率分别为68．0％、32．0％,对照组分别为66．9％、33．1％,两组比较,差异无统计学意义(P＞0．05);卵巢癌组1G／1G、1G／2G和2G／2G3种基因型频率分布分别为16．4％、31．1％和52．5％,对照组分别为16．6％、33．1％和50．3％,两组比较,差异无统计学意义(P＞0．05);与1G／1G基因型相比,2G／2G和2G／2G 1G／2G基因型经年龄校正的卵巢癌发病的OR分别为1．05(95％ CI=0．53～2．07)和1．00(95％ CI=0．52～1．90)。MMP-3的5A、6A等位基因频率在卵巢癌组和对照组中分别为17．2％、82．8％和20．2％、79．8％,两组比较,差异无统计学意义(P＞0．05);5A／5A、5A／6A、6A／6A基因型频率分布在两组间也无明显差异,两组相比,差异无统计学意义(P＞0．05);与6A／6A基因型相比,5A／5A 5A／6A基因型经年龄校正的卵巢癌发病的OR为1．34(95％ CI=0．81～2．23)。MMP-1的2G等位基因和MMP-3的6A等位基因存在完全连锁不平衡(X^2=56．53,P＜0．01)。结论 MMP-1的1G或2G基因多态性及MMP-3的5A或6A基因多态性与卵巢癌的遗传易感性无关。     

Genetic polymorphisms of GSTM1, p21, p53 and HPV infection with cervical cancer in Korean women

OBJECTIVES: The aim of this study was to determine whether GSTM1 or GSTT1 might be associated with risk of cervical cancer development in Korean women. The multiplicative interaction of GSTM1 and GSTT1 genotype with p21, p53 polymorphism, and HPV genotype was also investigated. METHODS: From 1997 to 1999, uterine cervical carcinoma was diagnosed in 215 Korean women at the Department of Obstetrics and Gynecology of Seoul National University Hospital. None of the women in the control groups (n = 98) had any evidence of cervical lesions, which were confirmed by Pap smear. Finally, 81 cases and 86 controls were genotyped for p21, p53, and GSTM1 and T1 and HPV infection. A multiplex PCR method was used for the genotyping of GSTM1 and GSTT1; direct sequencing for p53 codon 72, high-risk HPV, and PCR-RFLP (BsmAI) for p21 codon. The unconditional logistic regression analysis was used to calculate ORs and 95% CI. RESULTS: Although the GSTM1 and GSTT1 genotype was not significantly associated with cervical cancer development for all women, the GSTM1 null genotype was significantly associated with an increased risk of cervical cancer development in women with high-risk HPV infection (OR = 2.9, 95% CI: 1.0-8.2). Although the frequency of overall GSTT1 null genotype was significantly lower in cervical carcinoma patients with high-risk HPV infection (OR = 0.3, 95% CI: 0.1-1.0), almost 2-fold increased risk was observed among women with GSTT1 null and Arg/Arg genotype (OR = 1.9, 95% CI: 0.7-5.4). Although the cervical cancer risk was 3.3-fold increased in women with null and Arg/Arg genotype compared to women with GSTM1 present and p21 Ser-containing genotype, there was no significant multiplicative interaction between GSTM1 and p21 (P for interaction = 0.785) or p53 (P for interaction = 0.815). CONCLUSIONS: These findings suggest that the risk of cervical cancer may be related to GSTM1 genotype in women with high-risk HPV infection and that there is a possible gene-gene interaction in the incidence of cervical cancer.     

Germline polymorphism of p53 codon 72 in gynecological cancer

OBJECTIVE: To investigate the biological significance of single nucleotide polymorphism at codon 72 of the p53 gene in the development of gynecological cancer. METHODS: p53 codon 72 polymorphism was examined in a total of 354 blood samples from 95 normal, 83 cervical, 108 endometrial and 68 ovarian cancer cases using polymerase chain reaction and restriction fragment length polymorphism techniques. RESULTS: When p53 codon 72 genotype was classified into two subgroups of Arg/Arg and Arg/Pro + Pro/Pro, the Arg/Arg genotype was associated with an increased risk for the development of endometrial cancer (OR = 1.86, 95% CI = 1.06 to 3.26) compared with the Arg/Pro + Pro/Pro genotype (P = 0.0301). The Arg allele also increased the risk of endometrial cancer (OR = 1.42, 95% CI = 0.93 to 1.52) compared with the Pro allele, but no statistical difference was found (P = 0.1031). There was no significant difference in the genotype or allele prevalence between control subjects and cervical or ovarian cancer patients. CONCLUSION: Homozygous Arg at codon 72 of the p53 gene may be a risk factor for developing endometrial cancer in a Japanese population.