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。     

Transforming growth factor beta receptor I polyalanine repeat polymorphism does not increase ovarian cancer risk

OBJECTIVES: It has been suggested that the 6A allele of the type I TGFbeta receptor (TGFbetaR1) polyalanine repeat tract polymorphism may increase susceptibility to various types of cancer including ovarian cancer. METHODS: The TGFbetaR1 polyalanine polymorphism was genotyped in 588 ovarian cancer cases and 614 controls from a population-based case-control study in North Carolina. RESULTS: Significant racial differences in the frequency of the 6A allele were observed between Caucasian (10.7%) and African-American (2.4%) controls (P < 0.001). One or two copies of the 6A allele of the TGFbetaR1 polyalanine polymorphism was carried by 18% of all controls and 19% of cases, and there was no association with ovarian cancer risk (OR = 1.07, 95% CI 0.80-1.44). The odds ratio for 6A homozygotes was 1.81 (95% CI 0.655.06), but these comprised only 0.98% of controls and 1.70% of cases. CONCLUSIONS: The 6A allele of the TGFbetaR1 polyalanine polymorphism does not appear to increase ovarian cancer risk. Larger studies would be needed to exclude the possibility that the small fraction of individuals who are 6A homozygotes have an increased risk of ovarian or other cancers.     

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.     

A polymorphism in the matrix metalloproteinase-1 gene promoter is associated with the prognosis of patients with ovarian cancer

OBJECTIVE: The enzyme matrix metalloproteinase (MMP)-1 is involved in ovarian carcinogenesis. A common guanine insertion-deletion promoter polymorphism within the gene encoding MMP-1 (MMP1) has been suggested to be a candidate gene for ovarian cancer. We investigated whether this common polymorphism can also serve as independent prognostic parameter in a large series of affected women. METHODS: The MMP1 promoter polymorphism was examined in 151 Caucasian patients with epithelial ovarian cancer using polymerase chain reaction. Results were correlated with clinical data. RESULTS: No associations were ascertained between the MMP1 polymorphism and tumor stage (P = 1.0, odds ratio [OR] 1.08), lymph node involvement (P = 1.0, OR 0.8), tumor grading (P = 0.2, OR 0.5), and patient's age at diagnosis (P = 1.0, OR 1.04). Besides the clinically established prognosticators, tumor stage and histological grade, presence of the MMP1 polymorphism was associated with a shortened disease-free and overall survival in a univariate Kaplan-Meier analysis (P = 0.01) and a multivariate Cox regression model (P = 0.04). CONCLUSION: Presence of the MMP1 gene promoter polymorphisms was found to be a negative prognostic parameter in patients with ovarian cancer.     

Matrix metalloproteinase-1 promoter polymorphism and epithelial ovarian cancer: does ethnicity matter?

AIM: To estimate the relationship between matrix metalloproteinase (MMP)-1 promoter -1607 bp polymorphism and the risk of epithelial ovarian cancer (EOC) in Korean women and to clarify the ethnic difference in genotype distribution of this polymorphism. METHODS: Single nucleotide polymorphism (SNP) of MMP-1 promoter -1607 region in 133 EOC patients and 332 cancer-free patients were investigated. Then the associations of this polymorphism with EOC or its clinicopathological parameters were analyzed. In addition, genotype distributions of this polymorphism in Korean women were compared with those of other races by extracting data from the previously published literature. RESULTS: We found no relationship between MMP-1 promoter -1607 bp polymorphism and epithelial ovarian cancer in a Korean population. Furthermore, we found ethnicity-dependent differences in genotype distributions and allele frequencies by comparison with previous articles on this topic. We report significant ethnic differences in the genotype distributions and allele frequencies of the MMP-1 promoter -1607 bp polymorphism. CONCLUSION: Our results indicate that MMP-1-1607 bp polymorphism shows ethnic diversity, and that the hypothesis that this polymorphism is associated with epithelial ovarian cancer is not supported by this study in a Korean population. Moreover, this finding concurs with results obtained in white Americans and Europeans.     

The prohibitin 3' untranslated region polymorphism is not associated with risk of ovarian cancer

OBJECTIVE: The 3' untranslated region of the prohibitin gene encodes an RNA molecule that arrests cell proliferation between the G(1) and S phases of the cell cycle, and a C-to-T transition within this region creates a variant lacking antiproliferative activity. The T allele was reported to be associated with an increased risk of breast cancer in North American women, specifically in those under age 50 years reporting a first-degree family history of breast cancer. We assessed the association of the prohibitin 3' untranslated region polymorphism with risk of ovarian cancer in the Australian population by case-control comparison. METHODS: We examined 553 cases of epithelial ovarian cancer and 300 unaffected controls to assess whether this polymorphism was associated with risk of ovarian cancer in Australian women. Genotyping was carried out using the Perkin-Elmer ABI Prism 7700 Sequence Detection System for fluorogenic polymerase chain reaction allelic discrimination. Genotype distributions were compared by logistic regression. RESULTS: Stratification of the ovarian cancer cases according to tumour behavior (low malignant potential or invasive), histology, grade, stage, or p53 immunohistochemical status failed to reveal any heterogeneity with respect to prohibitin genotype. There was no difference in genotype distribution between cases and controls, with an odds ratio (95% confidence interval) of 0.99 (0.72-1.35) for the CT/TT genotype. CONCLUSION: The prohibitin T variant does not appear to be associated with risk of ovarian cancer in Australian women.     

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.     

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.     

A polymorphism in the matrix metalloproteinase-1 gene promoter is associated with the presence of polycystic ovary syndrome in Caucasian women

A common -1607 GG/G polymorphism of the matrix metalloproteinase-1 (MMP1) gene promoter was investigated in a series of Caucasian women with polycystic ovary syndrome (PCOS) and controls, by direct sequencing. In this prospective case-control study, the odds for women with at least one mutant GG allele of the MMP1 promoter to be diagnosed with PCOS was 2.7.     

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。     

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.     

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.     

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.     

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.     

Serotonin receptor 1A C(-1019)G polymorphism associated with premenstrual dysphoric disorder

OBJECTIVE: To assess whether the G allele of the serotonin receptor 1A C(-1019)G polymorphism is associated with premenstrual dysphoric disorder. METHODS: The study sample comprised 53 women with clinically diagnosed premenstrual dysphoric disorder (age range 27-46 years, mean 37.7 years) and 51 healthy control subjects (age range 22-48 years, mean 36.2 years). The serotonin receptor 1A C(-1019)G polymorphism was genotyped and compared between the two groups. RESULTS: In contrast to the postulated "high-risk" G/G genotype, there was a marked overrepresentation of the C/C genotype in the premenstrual dysphoric disorder group (P=.034; odds ratio 3.63, 95% confidence interval 1.22-10.78). The presence of at least one C allele was associated with a 2.5-fold increased risk of premenstrual dysphoric disorder (P=.053; odds ratio 2.46, 95% confidence interval 1.03-5.88). CONCLUSION: Our hypothesis that the high-risk G allele is associated with the occurrence of premenstrual dysphoria was not proved in this study. However, due to the increased prevalence of the C variant, we suggest that the C(-1019) allele may contribute to the risk of premenstrual dysphoria. LEVEL OF EVIDENCE: II.     

Functional SNP -1562C/T in the promoter region of MMP9 and recurrent early pregnancy loss

Angiogenesis, invasion and decidualization play an important role in uterine preparation and embryo development. Matrix metalloproteinases (MMP) are crucial for the degradation/remodelling of the extracellular matrix and are involved in spiral artery formation and invasion of endometrium during implantation. A functional single-nucleotide polymorphism (SNP) in the MMP9 promoter, 1562C/T, is known to influence expression in an allele-specific manner. The present study evaluated the association between maternal genotype of SNP 1562C/T of MMP9 and recurrent early pregnancy loss (REPL) risk. This case–control study was comprised of REPL patients (n = 106) and women having one healthy child as controls (n = 111). Genotyping for SNP 1562C/T of MMP9 was performed by PCR/restriction fragment length polymorphism followed by DNA sequencing. Allele and genotype distribution did not differ significantly between patients and controls (by allele, chi-squared 0.228, odds ratio 1.12, 95% confidence interval 0.695–1.816; by genotype, chi-squared 0.893). Thus SNP 1562C/T of MMP9 was not associated with REPL risk in this population and further study in other populations will verify whether it is associated with REPL risk or not. REPL is a multifactorial pathology and other genetic or environmental factors may be contributing to the complex aetiology of REPL.     

Protective role of the polymorphism CCR2-64I in the progression from squamous intraepithelial lesions to invasive cervical carcinoma

OBJECTIVE: Invasive cervical cancer (ICC) is one of the most common malignant diseases among women, representing almost 10% of all the cancers in the female population. The aim of this study was to explore the association of the CCR2-64I polymorphism with the risk of developing invasive cervical cancer (ICC) from squamous intraepithelial lesions (SILs). METHODS: DNA samples were extracted from peripheral blood cells of 109 patients with squamous intraepithelial lesions (28 low-grade and 81 high-grade cases) and 217 patients with ICC. The CCR2-64I polymorphism was analyzed through polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) (BseJI). The odds ratio (OR) and its 95% confidence interval (CI) were calculated as a measure of the association between CCR2-64I genotypes and cervical cancer risk. RESULTS: The frequency of the G/A genotype was significantly higher in SIL patients (n = 109) than ICC patients (n = 217) (P = 0.005; OR = 0.42; 95% CI: 0.22-0.83). Furthermore, no association was found when we analyzed the influence of the A allele in the progression from low-grade SIL (LSIL) to high-grade SIL (HSIL) (OR = 1.05; 95% CI = 0.370-2.98; P = 0.930), but a statistically significant association was found in the progression from high-grade SIL to ICC (OR = 0.435; 95% CI = 0.222-0.854; P = 0.014). CONCLUSION: These findings suggest that CCR2-64I polymorphism might have a protective role in the evolution from high-grade SIL to ICC.     

Risk factors for ovarian cancer in Taiwan: a case-control study in a low-incidence population

OBJECTIVE: We conducted a case-control study to identify risk factors for ovarian cancer in Taiwan, a low-incidence population where the incidence has been on the rise. METHODS: Cases were 86 women (age range 20-75, median 47) drawn from patients with primary, invasive epithelial ovarian cancer diagnosed between 1993 and 1998 in the Taipei metropolitan area, with the following histologic subtypes: 35% serous, 27% mucinous, 21% endometrioid, 15% clear cell, and 2% unspecified adenocarcinoma. Controls were 369 women (age range 20-75, median 44) selected from patients who were hospitalized at the same time for treatment of unrelated diseases. Subjects were interviewed in person regarding sociodemographic and reproductive characteristics, family and medical history, and diet. RESULTS: A strong inverse relationship of ovarian cancer to each live birth was observed (odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.20-0.89; OR = 0.30, 95% CI = 0.13-0.69; and OR = 0.18, 95% CI = 0.05-0.62 for parity of 1 or 2, 3-5, and >5, respectively). Menopause was associated with increased risk of disease (OR = 2.15, 95% CI = 1.21-3.83). A trend toward protection was seen with breastfeeding for more than 1 year (OR = 0.55, 95% CI = 0.29-1.01). No dietary factor was associated with an increased disease risk. Milk intake was associated with a decreased disease risk (OR = 0.45, 95% CI = 0.28-0.74). CONCLUSION: The strong protective effect of parity was supported by this study, and the decline in parity is likely an important reason for the rising incidence of ovarian cancer in Taiwan. A decreased disease risk was also seen with milk intake. In addition, the difference in the distribution of histologic subtypes in this population compared with high-incidence populations may point to further differences in risk factors.