Risk Of Epithelial Ovarian Carcinoma Research Articles

Establishment and verification of the nomogram that predicts the 3-year recurrence risk of epithelial ovarian carcinoma

BackgroundAs we all know, patients with epithelial ovarian carcinoma have poor prognosis and high recurrence rate. It is critical and challenging to screen out the patients with high risk of recurrence. At present, there are some models predicting the overall survival of epithelial ovarian carcinoma, however, there is no widely accepted tool or applicable model predicting the recurrence risk of epithelial ovarian carcinoma patients. The objective of this study was to establish and verify a nomogram to predict the recurrence risk of EOC.MethodsWe reviewed the clinicopathological and prognostic data of 193 patients with EOC who achieved clinical complete remission after cytoreductive surgery and chemotherapy between January 2003 and December 2013 in Peking University First Hospital. The nomogram was established with the risk factors selected by LASSO regression. The medical data of 187 EOC patients with 5-year standard follow-up in Peking University Third Hospital and Beijing Obstetrics and Gynecology Hospital were used for external validation of the nomogram. AUC curve and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration.ResultsThe nomogram for 3-year recurrence risk was established with FIGO stage, histological grade, histological type, lymph node metastasis status and serum CA125 level at diagnosis. The total score can be obtained by adding the grading values of these factors together. The C statistics was 0.828 [95% CI, 0.764–0.884] and the Chi-square value is 3.6 (P = 0.731 > 0.05) with the training group. When the threshold value was set at 198, the sensitivity, specificity, positive predictive value, negative predictive value and concordance index were 88.8, 67.0, 71.8, 86.3% and 0.558 respectively. In the external validation, the C statistics was 0.803 [95%CI, 0.738–0.867] and the Chi-square value is 11.04 (P = 0.135 > 0.05). With the threshold value of 198, the sensitivity, specificity, positive predictive value, negative predictive value and concordance index of the nomogram were 75.7, 77.0, 83.2, 67.9%, and 0.52 respectively.ConclusionsWe established and validated a nomogram to predict 3-year recurrence risk of patients with EOC who achieved clinical complete remission after cytoreductive surgery and chemotherapy. This nomogram with good discrimination and calibration might be useful for screening out the patients with high risk of recurrence.

The Effect of Polymorphisms of Estrogen Receptor βRS1271572 to the Incidence of Epithelial Ovarian Carcinoma

Objective: To determine the effect of polymorphism of estrogen receptor β to the risk of epithelial ovarian carcinoma at Dr. Mohammad Hoesin Hospital Palembang
 Methods: This population-based case control study included 40 women with epithelial ovarian carcinoma and 40 controls, from January 2010 until December 2011. Data analysis was performed by Chi Square test.
 
 Results: Distribution of estrogen receptor beta genotypes, both GT and TT (wild type-mutant and mutant), among case subjects was significantly higher than control (24 subjects {60%} vs. 5 subjects {12.5%}). The genotype effect was statistically significant for rs1271572 (OR=2.636; p=0.039) with Chi Square analysis. Whereas
 the allotype effect was also statistically significant (OR=1.949; p= 0.047).
 
 Conclusion: Polymorphism of estrogen receptor β may play a role in the risk of epithelial ovarian carcinoma at Dr. Mohammad Hoesin Hospital Palembang.
 [Indones J Obstet Gynecol 2012; 36-1:32-6]
 
 Keywords: epithelial ovarian carcinoma, polymorphism of estrogen receptor β, risk factor of ovarian carcinoma

Endometriosis-Associated Ovarian Cancer: A Review of Pathogenesis

Endometriosis is classically defined as the presence of endometrial glands and stroma outside of the endometrial lining and uterine musculature. With an estimated frequency of 5%–10% among women of reproductive age, endometriosis is a common gynecologic disorder. While in itself a benign lesion, endometriosis shares several characteristics with invasive cancer, has been shown to undergo malignant transformation, and has been associated with an increased risk of epithelial ovarian carcinoma (EOC). Numerous epidemiologic studies have shown an increased risk of EOC among women with endometriosis. This is particularly true for women with endometrioid and clear cell ovarian carcinoma. However, the carcinogenic pathways by which endometriosis associated ovarian carcinoma (EAOC) develops remain poorly understood. Current molecular studies have sought to link endometriosis with EAOC through pathways related to oxidative stress, inflammation and hyperestrogenism. In addition, numerous studies have sought to identify an intermediary lesion between endometriosis and EAOC that may allow for the identification of endometriosis at greatest risk for malignant transformation or for the prevention of malignant transformation of this common gynecologic disorder. The objective of the current article is to review the current data regarding the molecular events associated with EAOC development from endometriosis, with a primary focus on malignancies of the endometrioid and clear cell histologic sub-types.

Polymorphisms of Receptor for Advanced Glycation end Products and Risk of Epithelial Ovarian Cancer in Chinese Patients

Background: Given the roles of receptor for advanced glycation end products (RAGE) in the pathogenesis of carcinogenesis, we propose that RAGE polymorphisms may be associated with risk of epithelial ovarian carcinoma (EOC). Method: This case-control study included 190 women over 40 years of age who were diagnosed with primary EOC and 210 healthy control subjects. RAGE gene polymorphisms, including 82G>S,-374T>A,-429C>T,and 1704G>T were determined. Results: We found that only the frequencies of the 82G>S polymorphisms were significantly different between the EOC cases and controls. The 82SS genotype was significantly higher in EOC patients than in controls (37.89% vs. 23.33%,P<0.001). With the 82 GG genotype as reference, the OR for 82SS homozygous carriers reached to 2.65 (95% CI: 1.54-4.58; P =0.0004) after adjustment for age, smoking status, body mass index, family history, usage of contraceptives, tubal ligation history, use of menopausal hormones and menopausal status. The 82S allele carriage presented a higher risk for EOC (OR=1.71; 95% CI, 1.29-2.26; P=0.0002). The polymorphisms of 1704G>T,-374T>A and -429C>T did not affect the EOC risk. Conclusion: This result suggests that the 82G>S polymorphism of RAGE gene may be associated with the susceptibility of EOC.

The Functional Polymorphisms on Promoter Region of Matrix Metalloproteinase-12, -13 Genes May Alter the Risk of Epithelial Ovarian Carcinoma in Chinese

Growing evidences indicate that single nucleotide polymorphisms (SNPs) of matrix metalloproteinases (MMPs) gene promoter may alter MMPs protein expression levels to influence malignant tumors developing and progressing. Our study was to assess the effects of the SNPs in the promoter region of MMP-12 and MMP-13 on the risk of epithelial ovarian carcinoma (EOC) developing and progressing. MMP-12 A-82G and MMP-13 A-77G SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism in 256 EOC patients and 329 controls. The A/G genotype frequency of MMP-12 was significantly higher in patients than in controls (7.0% vs 3.3%, P = 0.04); similarly, the frequency of MMP-12 82G allele was higher in patients too (P = 0.04). Compared with A/A genotype, A/G genotype significantly increased the risk of EOC (odds ratio, 2.19; 95% confidence interval, 1.01-4.72). Age-stratified analysis showed that individuals with A/G genotype had a higher risk in the final diagnosis aged younger than 50 years. We observed no overall association between MMP-13-77A/G polymorphism and EOC. However, an elevated positive association was observed for A/A versus G/G + A/G genotypes in mucinous ovarian cancer. Combining the analyzed 2 SNPs, the haplotype distributions in patients were not significantly different from that in controls. These results suggested that the G allele of the MMP-12 82A/G polymorphism might be a risk factor for the development and progression of EOC and that the A/A genotype of MMP-13-77A/G polymorphism was associated with special pathological subtype and clinical stage in EOC at least in Chinese women.

Genetic polymorphisms in the estrogen receptor beta (ESR2) gene and the risk of epithelial ovarian carcinoma

Ovarian cancer is influenced by exogenous and endogenous estrogens as suggested by experimental and epidemiological evidence. Estrogen receptor beta is a predominant estrogen receptor in the normal ovary. Polymorphisms in the estrogen receptor beta gene (ESR2) might influence epithelial ovarian risk through regulation of cell proliferation and apoptosis. This population-based case-control study included 313 women with epithelial ovarian carcinoma and 574 controls, frequency-matched on age and ethnicity. Unconditional logistic regression was used to test associations of rs1271572, rs1256030, rs1256031, and rs3020450 ESR2 genotypes with ovarian cancer risk. Compared to homozygous common allele carriers, homozygous carriers of variant alleles for rs1271572 [odds ratio (OR) = 1.79, 95% confidence interval (CI):1.15-2.79, p global = 0.01] and rs1256030 [OR = 1.67, CI: 1.08-2.59, p global = 0.04], and women with haplotypes, including variant alleles of rs1271572, rs1256030, and rs1256031 SNPs [OR = 1.75, CI: 1.17-2.63, p global = 0.007], had significantly increased risk of ovarian carcinoma. The association of the rs1271572 genotype was strongest among women who had never used contraceptive steroids (p for interaction = 0.04). Our data suggest that ESR2 might be a susceptibility marker for epithelial ovarian cancer.

The protective side of progesterone

According to Jerry's commentary [1], exogenous oestrogen and progesterone potently inhibit tumorigenesis, representing an interesting strategy to prevent breast cancer, but we feel that the concerns noted by Jerry deserve further comment. According to the Million Women Study [2], when progesterone was included in the hormone replacement therapy (HRT) formulation, the odds ratio fell from 1.3 to 1.1, indicating a protective effect exerted by progesterone, though no significant difference in the relative risk of ovarian cancer was registered in the subgroups of women who used oestrogen only compared with those who used the combination. Long durations of use of unopposed oestrogen and of oestrogen plus progestin, especially sequential regimens, have been reported to be associated with increased ovarian cancer risk. In preclinical models, combined progestins circumvent the anti-apoptotic action of the long isoform of Fas-associating protein with death domain-like interleukin-1 beta-converting enzyme (FLICE)-like inhibitory protein, an anti-apoptosis mediator, representing an effective therapy for ovarian cancer cells [3]. In premenopausal women, combined oral contraceptives (OC) have been described to be effective at decreasing the risk of epithelial ovarian carcinoma, even though the strongest risk reduction has been associated either with low- or high-potency progestin formulations. Some synthetic progestins, when added to oestrogen in HRT for menopausal symptoms, have been reported to increase the risk of breast cancer more than oestrogen alone. Progestin use in breast cancer survivors is associated with an increased breast cancer risk compared with its non-use [4]. However, outside pregnancy, progesterone endogenously produced or exogenously administered does not have a cancer-promoting effect on breast tissue. The greater breast cancer risk related to the use of HRT containing oestrogen and synthetic androgenic progestin (19-nortestosterone derivatives) could be due to the non-progesterone-like effects enhancing the oestrogen proliferative effect on oestrogen-sensitive cancer cells. In postmenopausal women, progesterone is added to prevent the carcinogenic effect of oestrogen on the uterus [5]. In premenopausal women, the potency of the progestin in most OC appears adequate to provide a protective effect against endometrial cancer. Higher progestin-potency OC may be more protective than lower progestin potency OC among women with a larger body habitus. Progestagens counteract the adverse effect of oestrogens on the endometrium, the effect being greater the more days every month that they are added to oestrogen and the more obese that women are. Finally, because hormones may play a crucial role in the development of breast, endometrial and ovarian cancer, the impact on cancer risk of progestins included in HRT or OC formulations remains a major interest.

Association of Estrogen and Progestin Potency of Oral Contraceptives With Ovarian Carcinoma Risk

To estimate the association of the estrogen and progestin potency of combined oral contraceptive pills (OCPs) with epithelial ovarian carcinoma risk. This population-based case-control study included 745 women with incident, histologically confirmed epithelial ovarian carcinoma and 943 controls, matched on age and ethnicity. Data were collected using a standard questionnaire, picture albums, and calendars. The association of OCP potency with epithelial ovarian carcinoma risk was modeled using unconditional logistic regression. When compared with women who never used hormonal contraception, users of OCPs with low estrogen (equal to or less than 0.035 mg ethinyl estradiol) and low progestin (less than 0.3 mg norgestrel) were at significantly reduced risk of ovarian carcinoma (odds ratio 0.19; 95% confidence interval 0.05-0.75). The risk among these women was lower than among users of estrogen or progestin of high potency, but the difference was not statistically significant. However, in a subset of 205 women who reported exclusive use of norethindrone, users of 0.5 mg or less, had a significantly reduced risk of ovarian cancer compared with women using 10 mg of this progestin. Increased norethindrone dose resulted in a significant increase in ovarian carcinoma risk, indicating a dose-response association. Combined OCPs were effective at decreasing the risk of epithelial ovarian carcinoma, with the strongest risk reduction associated with low-potency formulations. II.

Diagnostic x-rays and risk of epithelial ovarian carcinoma in Jews.

To test the hypothesis that there would be ethnic differences in susceptibility to ionizing radiation from diagnostic x-rays. In a hospital-based study we compared reports of diagnostic x-rays to the lower abdomen and pelvis in incident cases of epithelial ovarian carcinoma (N = 161), community controls (N = 156) and convenience controls (N = 87). Thirty-nine per cent of cases and 31% of controls recalled x-rays more than 10 years before; 27% of cases and 14% of controls reported four Jewish grandparents. Comparing the cases with community controls, the odds ratio (95% confidence interval) for Jews versus non-Jews among women reporting no x-rays was 1.02 (0.37-2.79); among women reporting x-rays the estimate for Jews was 8.91 (2.00-39.6). Consistent results were seen with inclusion of convenience controls. Jewish cases reported an excess of pelvic diagnostic x-rays from age 20 onward and an excess of barium enemas and pyelograms. These preliminary findings require confirmation in other studies. They suggest that the known excess risk of this carcinoma in Jews might be associated with exposure to x-rays and add to a previous observation of an altered susceptibility to ionizing radiation in Jews. If confirmed, they would suggest a need for continued vigilance to evaluate the risks and benefits of diagnostic x-rays in individuals, regardless of ethnic origin, who might carry mutations in DNA repair genes.

Hormone replacement therapy formulations and risk of epithelial ovarian carcinoma.

Hormone replacement therapy (HRT) has been inconsistently linked to ovarian cancer. Estrogen formulations in HRT vary in their effects on estrogen-sensitive target tissues, such as the ovary. The aim of the study is to evaluate the impact of various HRT formulations and their characteristics of use on the risk of epithelial ovarian carcinoma (EOC). We assessed the association between the use of HRT and the risk of invasive EOC in women participating in a population-based, case-control study conducted in the Delaware Valley from 1994 to 1998. Cases aged 45 or above at diagnosis (n = 484) were compared to community controls (n = 926) frequency matched by age and area of residence. Information on HRT formulation, timing, and duration were obtained by in-person interview by trained interviewers. HRT formulations were classified as opposed (estrogen + progestin) or unopposed (estrogen alone). They were further categorized according to the estrogen component as either conjugated equine estrogen (CEE), the most common formulation, or non-CEE. Multivariate unconditional logistic regression analyses were used to adjust for age at diagnosis, number of live births, use of oral contraceptives, family history of ovarian carcinoma, and history of tubal ligation. Overall, no association was found between any use of HRT and EOC. Although use of unopposed non-CEE was associated with a significant decrease in risk among hysterectomized women (OR = 0.17, 95% CI = 0.04,0.82), this was not true for women with an intact uterus (OR = 1.14, 95% CI = 0.44,2.98; P for interaction = 0.049). No significant differences in EOC risk were observed for other HRT formulations. Our results did not suggest any consistent pattern of altered risk for EOC and the overall use of HRT by specific formulations of HRT.

Family History of Reproductive Cancers and Ovarian Cancer Risk: An Italian Case-Control Study

The relation between family history of ovarian, breast, and endometrial cancer and risk of epithelial ovarian carcinoma was analyzed within the framework of a case-control study conducted from 1983 to 1989. The study included 755 cases of ovarian cancer and 2,023 controls in hospital for a spectrum of acute nongynecologic, hormonal, or neoplastic conditions in the Greater Milan area, Italy. Eighteen cases (2%) and 24 controls (1%) reported a history of ovarian cancer in a first-degree relative: The corresponding multivariate adjusted odds ratio (OR) was 1.9 (95% confidence interval (CI) 1.1-3.6). The risk of ovarian cancer was elevated in women reporting a family history of breast cancer (OR = 1.6, 95% CI 1.1-2.3), but no significant association emerged with a family history of endometrial cancer (OR = 1.3, 95% CI 0.8-1.7). When the data were stratified by family history of breast cancer, a family history of ovarian cancer was over 10 times more frequent in both cases and controls who reported a family history of breast cancer than in cases and controls reporting no family history of breast cancer. The estimated odds ratio for ovarian cancer associated with a family history of the disease was 2.3 (95% CI 1.1-4.5) in women not reporting a family history of breast cancer, but no association emerged in the subgroup of women reporting a family history of breast cancer. These results confirm that a family history of ovarian cancer increases the risk of the disease, but the percentage of ovarian cancer cases explained by a family history of the disease is small: Less than 1% of observed cases in this study could be attributed to this "family risk factor."