p53基因多态性与卵巢上皮性癌发病风险的关系

目的　探讨中国北方汉族妇女卵巢上皮性癌 (卵巢癌 )易感性与 p5 3基因第 4外显子的第 72密码子和第 3内含子多态性的关系。方法　应用序列特异性引物 ,以PCR技术检测 12 4例卵巢癌患者 (卵巢癌组 )和 12 8例健康妇女 (对照组 )的p5 3基因第 4外显子的第 72密码子和第 3内含子的基因型。结果　卵巢癌组和对照组脯氨酸 (Pro)、精氨酸 (Arg)等位基因频率分别为 5 3 2 %、4 6 8%和 4 6 1%、5 3 9%,两组比较 ,差异无显著性 (χ2 =2 5 6 3,P =0 10 9) ;卵巢癌组Pro/Pro、Pro /Arg、Arg/Arg 3种基因型频率分别为 2 9 0 %、4 8 4 %、2 2 6 %,与对照组 (2 1 1%、5 0 0 %、2 8 9%)相比 ,差异也无显著性 (χ2 =2 5 98,P =0 2 73) ;按病理类型分类 ,浆液性癌和宫内膜样癌两者间或分别与对照组间 ,其基因型频率与等位基因频率比较 ,差异均无显著性 (P >0 0 5 ) ;按手术病理分期分类 ,Ⅲ～Ⅳ期卵巢癌患者Arg等位基因及Arg/Arg基因型频率明显高于Ⅰ～Ⅱ期卵巢癌患者 (χ2 =7 4 94 ,P =0 0 0 6和 χ2 =8 318,P =0 0 0 4 )。卵巢癌组及对照组p5 3基因第 3内含子 16bp插入或缺序列 (PIN3)的A、A′等位基因频率分别为 94 8%、5 2 %及 94 5 %、5 5 %,两组比较 ,差异无显著性(χ2 =0 0 13,P =0 910 ) ;两组     

广东籍汉族妇女N5,10-MTHFR基因和eNOS基因多态性与子痫前期和子痫相关性的研究

目的:探讨N5,10-亚甲基四氢叶酸还原酶(MTHFR)基因及内皮型一氧化氮合酶(eNOS)基因多态性与广东籍汉族妇女子痫前期和子痫发病的关系。方法:567例广东籍汉族妇女中54例诊断为子痫前期或子痫,513例为正常妊娠(对照组)。应用PCR-RFLP方法,检测567例早孕期妇女外周血MTHFR基因C677T突变和eNOS基因G894T突变,计算各基因型的相对风险率。结果:子痫前期和子痫组MTHFR C/C、C/T及T/T基因型频率分别为59.2%、20.4%及20.4%,其中T/T基因型频率显著高于对照组(5.5%)(P<0.001),并且T等位基因频率为30.6%,显著高于对照组(20.5%)(P<0.05),T/T基因型在子痫前期或子痫发病中的相对风险率为4.431。子痫前期和子痫组的eNOS基因频率与对照组无显著差异。结论:广东籍汉族妇女MTHFR基因C677T多态性可能与子痫前期或子痫发病的易感性相关,eNOS基因G894T多态性与子痫前期或子痫发病的易感性无关。     

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.     

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。     

E钙黏蛋白基因多态性与子宫颈癌易感性的关系

目的 探讨E钙黏蛋白(CDH1)基因3'-非翻译区终止密码子下游54 bp处C/T单核苷酸多态性(3'-UTR+54C/T SNP)与宫颈癌的易感性.方法 构建含CDH1基因3'-UTR+54C/TSNP DNA序列的荧光素酶表达载体,利用双荧光素酶报告基因检测系统观察CDH1基因3'-UTR+54C/T SNP转染后人胚肾细胞株293T细胞的荧光素酶活性(RLA);采用PCR-限制性片段长度多态性(RFLP)方法检测280例宫颈癌患者(病例组)和330例健康妇女(对照组)的CDH1基因3'-UTR+54C/T SNP的基因型及等位基因频率分布,进一步分析其与宫颈癌易感性的关系.结果 双荧光素酶报告基因检测系统观察显示,转染CDH1基因3'-非翻译区(3'-UTR)C等位基因后293T细胞的RLA平均为1.46,转染CDHl基因3'-UTR T等位基因后293T细胞的RLA平均为3.01,两者比较,差异有统计学意义(t=2.94,P=0.042).PCR-RFLP方法检测显示,CDH1基因3'-UTR C等位基因频率病例组为80.7%,明显高于对照组的74.5%(χ2=6.59,P=0.010).病例组T/T、T/C、C/C基因型频率分别为4.3%、30.0%、65.7%,对照组分别为5.8%、39.4%、54.8%,两组间比较.差异有统计学意义(χ2=7.45,P=0.024).与T/T或T/C基因型比较,携带C/C基因型者宫颈癌的发病风险明显增加(OR=1.578,95%CI=1.136～2.191).结论 CDH1基因3'-UTR C等位基因可能降低荧光素酶报告基因的表达;C/C基因型可能是宫颈癌发病的潜在危险因素.     

汉族妇女中p21 codon31单核苷酸多态性与宫颈癌易感性关系的研究

目的:研究汉族妇女中p21codon31单核苷酸多态性与宫颈癌易感性之间的关系。方法:用DNA抽提试剂盒从研究对象的外周血标本中抽提基因组DNA,其中宫颈癌患者226例(鳞状细胞癌215例,宫颈腺癌11例),正常对照组196例;用错配扩增突变检测PCR的方法测定p21codon31单核苷酸多态基因型。结果:宫颈鳞状细胞癌患者的p21codon31AGA(精氨酸)等位基因频率显著高于对照组(37.0%vs 24.0%,P<0.05,OR=1.9,95%CI=1.0~3.4);宫颈鳞状细胞癌与对照组之间的AGA/AGA、AGA/AGC和AGC/AGC等位基因型的分布差异有统计学意义,其中AGA/AGA(OR=2.5,95%CI=1.4~4.5)和AGA/AGC(OR=1.8,95%CI=1.6~2.8)等位基因型在宫颈鳞状细胞癌中的频率显著高于对照组。宫颈腺癌与对照组之间p21codon31单核苷酸多态性分布没有显著差异。结论:p21codon31AGA(精氨酸)等位基因可能是汉族妇女患宫颈鳞状细胞癌的一个危险因素。     

CYP1B1基因多态性与卵巢癌易感性的研究

目的:研究CYP1B1基因外显子2密码子119(G-T)、外显子3密码子432(C-G)多态性与卵巢癌遗传易感性的关系。方法:应用等位基因特异性聚合酶链反应(AS-PCR)法对53例卵巢癌患者和30例对照者进行CYP1B1基因密码子119(G-T)、密码子432(C-G)突变分析,用免疫组化SP法进一步研究雌激素受体(ER)、孕激素受体(PR)的表达,分析其是否受CYP1B1基因多态性的影响。结果:CYP1B1基因密码子432中等位基因C、G在卵巢癌组和对照组分布的差异有统计学意义(P<0.05),其中等位基因G使卵巢癌发病风险增加2.71倍。CYP1B1基因密码子432C/G各基因型分布两组间差异有统计学意义(P<0.01),纯合突变(G/G)基因型、杂合突变(C/G)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4.53倍和4.43倍。此外,432G/G、C/G基因型者ER阳性表达率高于432(C/C)基因型,三者间有显著差异(P<0.05)。结论:CYP1B1基因密码子432突变等位基因与卵巢癌的发生有一定关系,突变基因型增加了卵巢癌的发病风险,且与ER的表达相关。     

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。     

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。     

PAI-1、TGFβ1基因多态性与子宫内膜异位症相关性的研究

目的:探讨PAI-1基因启动子区4G/5G和TGFβ1基因-509C/T基因多态性与中国河北省汉族育龄妇女Ⅲ、Ⅳ期EMs遗传易感性的关系。方法:用病例对照研究法,75例Ⅲ、Ⅳ期EMs患者与82例对照组的外周血白细胞为样本,用PCR-RFLP技术分析PAI-1基因启动子区4G/5G和TGFβ1基因-509C/T基因多态性分布频率。结果:PAI-1基因-6754G/5G的3种基因型:4G/4G、4G/5G、5G/5G在EMs组和对照组的分布频率分别为:69.3%,28.0%,2.7%;12.2%,31.7%,56.1%。4G/5G等位基因在两组的分布频率为83.3%,16.7%;28.1%,71.9%。两组差异有统计学意义(P0.05)。TGFβ1基因-509C/T3种基因型:CC/CT/TT在EMs和对照组的分布频率分别为:10.7%,58.7%,30.7%;57.3%,41.5%,1.2%。C/T等位基因在两组的分布频率为40%,60%;78%,22%。两组差异有统计学意义(P0.05)。结论:携带PAI-1基因启动子区-6754G等位基因增加了患Ⅲ、Ⅳ期EMs的危险性。携带TGFβ1基因-509T等位基因患Ⅲ、Ⅳ期EMs的危险性增加。     

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.     

The prohibitin 3' untranslated region polymorphism in patients with ovarian cancer

OBJECTIVE: Prohibitin is an important antiproliferative protein inhibiting cell proliferation by blocking the G1/S transition of the cell cycle. Recent findings indicate that the presence of at least one mutant allele within a certain prohibitin gene polymorphism causes inactivation of bioactive RNA resulting in the loss of its pro-apoptotic function and a subsequent risk for malignant growth. Based on these findings we studied whether the presence of this prohibitin polymorphism increases the risk and worsens the prognosis of ovarian cancer in Caucasian women. STUDY DESIGN: A polymorphism within the 3' untranslated region (UTR) of the prohibitin gene was evaluated by pyrosequencing in 136 Caucasian patients with epithelial ovarian cancer and 129 healthy Caucasian controls. RESULTS: The wild-type C/C, heterozygous C/T, and the mutant T/T prohibitin genotype was found in 88 (64.7%), 46 (33.8%), and 2 (1.5%) patients with ovarian cancer and in 84 (65.1%), 39 (30.2%), and 6 (4.7%) healthy controls. Presence of at least one mutant allele of the prohibitin 3' UTR polymorphism was not associated with an increased risk of ovarian cancer as compared to healthy controls (P=0.9). No association was found between presence of the prohibitin 3' UTR polymorphism and the clinico-pathological parameters tumor stage, tumor grade, and patients' age at diagnosis. Presence of at least one mutant allele of the prohibitin 3' UTR polymorphism was not associated with disease-free and overall survival. CONCLUSION: The prohibitin 3' UTR polymorphism was not associated with risk and prognosis of ovarian cancer in Caucasian women.     

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.     

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.     

TrkB及其配体BDNF在卵巢上皮癌中的表达及其临床意义

目的检测酪氨酸激酶B（tyrosine kinase,TrkB）及其配体脑源性神经营养因子（brainderived neurotrophic factor,BDNF）在卵巢上皮癌（EOC）中的表达,并探讨其临床意义。方法选择中山大学附属肿瘤医院病理存档的石蜡标本108例,其中10例正常卵巢、17例良性卵巢肿瘤、21例卵巢交界性肿瘤和60例卵巢上皮癌,采用免疫组化链霉素抗生物素蛋白-过氧化物酶法（SP法）检测TrkB及其配体BDNF蛋白的表达水平,分析其与临床病理因素之间的关系。结果 TrkB和BDNF蛋白在正常卵巢组织和良性卵巢上皮性肿瘤中无表达;在交界性和卵巢上皮性癌中的阳性表达率分别为19.0%、71.7%和14.0%、51.7%（P〈0.05）。TrkB和BDNF蛋白在EOC组中的表达水平与其FIGO分期及病理分级有关,在Ⅲ期＋Ⅳ期、低分化组（G3）比Ⅰ期＋Ⅱ期、高中分化（G1、G2）组表达率高（P〈0.05）。TrkB和BDNF在卵巢上皮癌中的表达水平呈正相关（r=0.428,P〈0.05）。结论卵巢上皮癌中存在TrkB和BDNF的异常高表达。TrkB和BDNF可能协同作用促进了卵巢上皮癌的发生、发展,并有望成为卵巢上皮癌基因治疗的新靶点。     

Association between a functional single nucleotide polymorphism in the MDM2 gene and sporadic endometrial cancer risk

OBJECTIVES: MDM2 is an important negative regulator of the p53 tumor suppressor protein. A naturally occurring T/G single nucleotide polymorphism (SNP) in the MDM2 gene promoter, SNP309, causes an increase in MDM2 protein levels and impairment of p53 tumor suppressor activity. SNP309 occurs at a relatively high frequency in the general population and has been associated with accelerated tumorigenesis in hereditary Li-Fraumeni associated cancers as well as in sporadic soft tissue sarcomas. The objective of this study was to examine the association between SNP309 and sporadic endometrial cancer risk. METHODS: Genomic DNA was isolated from 73 patients with endometrial cancer and 79 healthy, female controls. The MDM2 gene promoter region was amplified by PCR and the SNP309 genotype determined by restriction enzyme digestion of the amplified DNA fragment. Unconditional logistic regression analysis was used to determine the relationship between genotypes and endometrial cancer risk and histopathologic features. RESULTS: The homozygous G/G genotype was found in 25% of endometrial cancer cases and 11% of controls. In an age-adjusted analysis of cases and controls, the G/G genotype increased the risk of endometrial cancer 2.76-fold (95% CI: 1.06, 7.20; p=0.03) compared to presence of a wild-type T allele (T/G and T/T genotypes). No association was found between the SNP309 G/G genotype and either endometrial cancer histology, grade, stage, or age at diagnosis. CONCLUSIONS: The MDM2 SNP309 homozygous G/G genotype may be a genetic variant that influences sporadic endometrial cancer susceptibility.     

Polymorphisms of interleukin (IL)-1α, IL-1β, IL-6, IL-10, and IL-18 and the risk of ovarian cancer

OBJECTIVE: Recent studies of ovarian cancer have suggested a role for inflammation in carcinogenesis. Data from a population-based case-control study in Hawaii were examined to assess the relation between polymorphisms in cytokines involved with the inflammatory response, specifically members of the interleukin (IL) family and the incidence of ovarian cancer. PATIENTS AND METHODS: The analysis of 182 epithelial ovarian cancer cases and 219 controls focused on the polymorphisms in the following genes: IL-1alpha, IL-1beta, IL-6, IL-10, and IL-18. Genotype data were obtained from blood samples collected in participants' homes, and reproductive, demographic, and lifestyle histories were collected during interview. RESULTS: There were no significant odds ratios (ORs) for ovarian cancer by allelic variants in any of the IL genes after adjusting for age, ethnicity, education, oral contraceptive pill use, pregnancy, and history of tubal ligation. Although there was a significantly reduced risk of ovarian cancer risk among women with an IL-1alpha (-4845) T allele compared to women with two G alleles (OR: 0.59; 95% confidence interval: 0.37-0.97) after adjustment for age and ethnicity, the trend was not significant (p = 0.10). Further examination of the data suggested that women with at least one IL-18 variant allele (a G to C transition at position -137) were at significantly decreased risk of advanced ovarian cancer (OR: 0.51; 95% confidence interval: 0.28-0.90) compared to women with the IL-18 GG genotype. There was a significant difference in the risk of ovarian cancer associated with the IL-18 C allele by stage at diagnosis (p = 0.04 for homogeneity in the ORs): cases with IL-18 GC or CC genotypes were less likely to be diagnosed at regional/distant stages. Analysis of the data within ethnic subgroups revealed a significant positive association of the heterozygous IL-18 GC genotype with ovarian cancer risk among Native Hawaiian women (OR: 9.96; 95% CI: 1.88-52.90). The OR for ovarian cancer was not significant for Native Hawaiian women homozygous for the IL-18 C allele, but only one case and control had the IL-18 CC genotype. CONCLUSIONS: Overall, this study does not support an association of selected IL-1alpha, IL-1beta, IL-6, IL-10, or IL-18 polymorphisms with the risk for ovarian cancer. However, the IL-18 G137C variant may be a marker for ovarian cancer progression or metastasis.