CYP1A1 polymorphism and risk of gynecological malignancy in Japan

2003 ◽  
Vol 13 (6) ◽  
pp. 785-790 ◽  
Author(s):  
T. Sugawara ◽  
E. Nomura ◽  
T. Sagawa ◽  
N. Sakuragi ◽  
S. Fujimoto
Keyword(s):  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
Cancer Patients ◽  
Japanese Population ◽  
Japanese Patients ◽  
Epidemiologic Studies ◽  
Cytochrome P450 1A1 ◽  
Gynecological Malignancy ◽  
Flanking Region ◽  
Cyp1a1 Polymorphism

The incidence of endometrial cancer and ovarian cancer in Japan has been increasing in recent years. Results of epidemiologic studies suggest that the onset and multiplication of these cancers are associated with estrogen. Estrogens are metabolized by cytochrome P450 1A1 (CYP1A1) and converted into catecholestrogens, which are carcinogens. CYP1A1 has several polymorphisms, the major one being T6235C transition in the non-coding 3′-flanking region (MspI polymorphism), and another being A4889G transition in exon 7 (Ile/Val polymorphism). These polymorphisms can affect the metabolites of estrogens and contribute to the susceptibility to gynecological malignancy. In this study, to determine whether CYP1A1 polymorphism plays a role in the development of gynecological malignancy in the Japanese population, we assessed the association of CYP1A1 polymorphism in Japanese patients with gynecological malignancy in comparison to that in controls. The odds ratios (ORs) of Ile/Val polymorphism were 1.16 in ovarian cancer patients and 1.70 in endometrial cancer patients. The ORs of MspI polymorphism were 1.33 in ovarian cancer patients and 0.88 in endometrial cancer patients. No significant association was found between these CYP1A1 polymorphisms and gynecological malignancy. Although the frequency of CYP1A1 polymorphism in the Japanese population is higher than that in the Caucasian population, CYP1A1 polymorphism is not related to gynecological malignancies in Japanese population.

186 Distinct immune signatures predicting clinical response to PD-1 blockade therapy in gynecological cancers revealed by high-dimensional immune profiling

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A200-A200
Author(s):  
Yuki Muroyama ◽  
Yuki Muroyama ◽  
Sasikanth Manne ◽  
Alexandar Huang ◽  
Divij Mathew ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Endometrial Cancer ◽  
T Cell ◽  
Clinical Response ◽  
Cancer Patients ◽  
T Cell Response ◽  
High Dimensional ◽  
Uterine Endometrial Cancer ◽  
Immune Profiling

BackgroundAlthough immune checkpoint blockade revolutionized cancer therapy, response rates have been mixed in gynecological malignancies. While uterine endometrial cancer with high microsatellite instability (MSIHI) and high tumor mutational burden (TMB) respond robustly to checkpoint blockade, high-grade serous ovarian cancer (HGSOC) with low TMB respond modestly. Currently, there has been no known immune signature or T cell phenotype that predicts clinical response in gynecological tumors.MethodsTo dissect the immune landscape and T cell phenotypes in gynecological cancer patients receiving PD-1 blockade, we used high-dimensional cytometry (flow cytometry and mass cytometry (CyTOF)). We performed longitudinal deep immune profiling of PBMC from patients with recurrent uterine endometrial cancer receiving single-arm nivolumab, and HSGOC patients receiving neoadjuvant nivolumab plus platinum-based chemotherapy prior to debulking surgery.ResultsChemotherapy-resistant MSI-H uterine cancer patients treated with nivolumab had a proliferative T cell response 2–4 weeks post PD-1 blockade, consistent with responses seen in high TMB melanoma and lung cancer. The responding Ki67+ CD8 T cell population was largely CD45RAloCD27hi or CD45RAloCD27lo and highly expressed PD1, CTLA-4, and CD39, consistent with the phenotype of exhausted T cells (TEX). These exhausted-like cells are enriched in responders, whereas early expansion Tregs are enriched in non-responders. Unlike patients with uterine endometrial cancer, patients with TMBlo ovarian cancer did not have a clear proliferative CD8 T cell response after neoadjuvant nivolumab plus chemotherapy treatment, suggesting systemic immune suppression. At baseline, ovarian cancer without recurrence have more terminally differentiated effector-like CD8 T cells, and patients with recurrence have more naive-like cells. Thus, both high and low TMB gynecological tumors have distinct immune landscapes associated with clinical response. Additionally, in MSI-H uterine endometrial cancer patients, the length of time between the prior chemotherapy and the initiation of immunotherapy was negatively correlated with T cell reinvigoration post immunotherapy and clinical response. This suggests the importance of optimize therapeutic timing to maximize the therapeutic efficacy when combining immunotherapy and chemotherapy.ConclusionsCollectively, our immune profiling revealed the distinct immune signatures associated with clinical response to PD-1 blockade in gynecological cancers. Our results also suggest that TMBhi inflamed versus TMBlo cold tumor microenvironment, and timing of chemo/immunotherapy could impact differentiation and functions of T cells.Ethics ApprovalThe study was approved by MSKCC Ethics Board, approval number 17–180 and 17–182.

scholarly journals CA125 and Ovarian Cancer: A Comprehensive Review

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3730
Author(s):  
Parsa Charkhchi ◽  
Cezary Cybulski ◽  
Jacek Gronwald ◽  
Fabian Oliver Wong ◽  
Steven A. Narod ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Point Of Care ◽  
Prognostic Indicator ◽  
Type I ◽  
Average Risk ◽  
Type Ii ◽  
Gynecological Malignancy ◽  
Primary Ovarian Cancer ◽  
Low Volume

Ovarian cancer is the second most lethal gynecological malignancy. The tumour biomarker CA125 has been used as the primary ovarian cancer marker for the past four decades. The focus on diagnosing ovarian cancer in stages I and II using CA125 as a diagnostic biomarker has not improved patients’ survival. Therefore, screening average-risk asymptomatic women with CA125 is not recommended by any professional society. The dualistic model of ovarian cancer carcinogenesis suggests that type II tumours are responsible for the majority of ovarian cancer mortality. However, type II tumours are rarely diagnosed in stages I and II. The recent shift of focus to the diagnosis of low volume type II ovarian cancer in its early stages of evolution provides a new and valuable target for screening. Type II ovarian cancers are usually diagnosed in advanced stages and have significantly higher CA125 levels than type I tumours. The detection of low volume type II carcinomas in stage IIIa/b is associated with a higher likelihood for optimal cytoreduction, the most robust prognostic indicator for ovarian cancer patients. The diagnosis of type II ovarian cancer in the early substages of stage III with CA125 may be possible using a higher cutoff point rather than the traditionally used 35 U/mL through the use of point-of-care CA125 assays in primary care facilities. Rapid point-of-care testing also has the potential for effective longitudinal screening and quick monitoring of ovarian cancer patients during and after treatment. This review covers the role of CA125 in the diagnosis and management of ovarian cancer and explores novel and more effective screening strategies with CA125.

scholarly journals Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Huan Wang ◽  
Qi Cheng ◽  
Kaikai Chang ◽  
Lingjie Bao ◽  
Xiaofang Yi
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Group ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Integrated Analysis ◽  
M2 Macrophage ◽  
Gynecological Malignancy

Ovarian cancer remains the most lethal gynecological malignancy. Ferroptosis, a specialized form of iron-dependent, nonapoptotic cell death, plays a crucial role in various cancers. However, the contribution of ferroptosis to ovarian cancer is poorly understood. Here, we characterized the diagnostic, prognostic, and therapeutic value of ferroptosis-related genes in ovarian cancer by analyzing transcriptomic data from The Cancer Genome Atlas and Gene Expression Omnibus databases. A reliable 10-gene ferroptosis signature (HIC1, ACSF2, MUC1, etc.) for the diagnosis of ovarian cancer was identified. Notably, we constructed and validated a novel prognostic signature including three FRGs: HIC1, LPCAT3, and DUOX1. We also further developed a risk score model based on these three genes which divided ovarian cancer patients into two risk groups. Functional analysis revealed that immune response and immune-related pathways were enriched in the high-risk group. Meanwhile, the tumor microenvironment was distinct between the two groups, with more M2 Macrophage infiltration and higher expression of key immune checkpoint molecules in the high-risk group than in the other group. Low-risk patients exhibited more favorable immunotherapy and chemotherapy responses. We conclude that crosstalk between ferroptosis and immunity may contribute to the worse prognosis of patients in the high-risk group. In particular, HIC1 showed both diagnostic and prognostic value in ovarian cancer. In vitro experiments demonstrated that inhibition of HIC1 improved drug sensitivity of chemotherapy and immunotherapy agents by inducing ferroptosis. Our findings provide new insights into the potential role of FRGs in the early detection, prognostic prediction, and individualized treatment decision-making for ovarian cancer patients.

scholarly journals Detection of MCM5 as a novel non-invasive aid for the diagnosis of endometrial and ovarian tumours

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
J. Stockley ◽  
R. Akhand ◽  
A. Kennedy ◽  
C. Nyberg ◽  
E. J. Crosbie ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
Cancer Patients ◽  
Vaginal Swab ◽  
Urine Samples ◽  
Surface Epithelium ◽  
Normal Epithelium ◽  
Non Invasive ◽  
Bodily Fluids ◽  
Significant Difference

Abstract Background MCM5 is a protein involved in DNA replication, facilitating cell proliferation. In normal epithelium MCM5 expression is restricted to the cells in the basal proliferative compartments, however in the presence of a tumour MCM5 positive cells are present at the surface epithelium and are shed into bodily fluids. The aim of this study was to determine the sensitivity of MCM5 as a biomarker for the detection of endometrial and ovarian cancer. Methods Patients with known ovarian or endometrial cancers, or known benign gynaecological conditions, were enrolled. Informed consent was obtained prior to the collection of full void urine, and either a vaginal tampon (worn for 6–8 h), or a vaginal swab. Vaginal secretions were extracted from the tampon or swab, centrifuged and lysed. Urine samples were centrifuged and lysed. MCM5 levels were determined by MCM5-ELISA (Arquer Diagnostics Ltd). Results 125 patients completed the study protocol, 41 patients had endometrial cancer, 26 ovarian cancer, and 58 benign controls. All patients provided a urine sample and either a tampon or vaginal swab sample. Urine MCM5 levels were higher in cancer patients than controls (p < 0.0001), there was no significant difference in levels between tampon samples or vaginal swab samples in cancer patients when compared to controls. Performance of MCM5 to discriminate cancer from benign disease was high with an area under the ROC curve of 0.83 for endometrial cancer and 0.68 for ovarian cancer. Using a cut off of 12 pg/mL, overall sensitivity for endometrial cancer was 87.8, and 61.5% for ovarian cancer with a specificity of 75.9%. Conclusions MCM5 is a novel sensitive and specific biomarker for the detection of ovarian and endometrial tumours in urine samples, which is likely to have clinical utility as a diagnostic aid.

scholarly journals GYNECOLOGICAL MALIGNANCY IN BPKMCH, BHARATPUR: A RETROSPECTIVE ANALYSIS OF 321 CASES

2003 ◽  
Vol 40 (139) ◽  
pp. 108-111
Author(s):  
Manohar Pradhan ◽  
H P Dhakal ◽  
C B Pun ◽  
S Pradhan ◽  
G Dangal
Keyword(s):  
Ovarian Cancer ◽  
Squamous Cell Carcinoma ◽  
Endometrial Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Age Group ◽  
Cancer Cervix ◽  
Gynecological Malignancy ◽  
Patients With Cancer ◽  
Carcinoma Of Cervix

Gynecological Malignancy is the leading cancer in female not only in Nepal butworldwide. A retrospective study of histopathological specimens was conducted inBPKMCH Bharatpur from July 1999 to January 2001, duration of 19 months. Total321 cases of Gynecological Malignancy were diagnosed in Department of Pathologyof BPKMCH. Out of which 272(84.73%) cases of cancer of cervix; 17 cases (5.29%)of cancer of vulva; 14 cases (4.36%) of ovarian cancer, 12 cases (3.73%) of cancer ofvagina and 6 cases (1.86%) of endometrial cancer were detected. Cancer of cervixwas most common in 40-49 years age group followed by 50-59 years age group. Meanage of the patients with cancer of cervix was 50 years and 10 months; minimum of 29years and maximum of 76 years. Out of 272 cases of cancer of cervix, 266 (97.79%)were squamous cell carcinoma and rest 6 (2.20%) were adenocarcinoma. Commonesthistology in vulva and vagina was squamous cell carcinoma, whereas adenocarcinomawas commonest in endometrium and ovary. The higher incidence of gynecologicalmalignancies particularly carcinoma of cervix was observed in BPKMCH.Key Words: Cancer, Cervix, Vagina, Vulva, Ovary.

Hormonal therapy in ovarian cancer

2007 ◽  
Vol 17 (2) ◽  
pp. 325-338 ◽  
Author(s):  
H. Zheng ◽  
J. J. Kavanagh ◽  
W. Hu ◽  
Q. Liao ◽  
S. Fu
Keyword(s):  
Ovarian Cancer ◽  
Hormonal Therapy ◽  
Experimental Studies ◽  
Epidemiologic Studies ◽  
Ovarian Cancer Cells ◽  
Gynecological Malignancy ◽  
Cancer Pathogenesis ◽  
Ovarian Carcinogenesis ◽  
Growth Inhibitory ◽  
Causative Factors

Ovarian carcinoma continues to be the leading cause of death due to gynecological malignancy. Epidemiologic studies indicate that steroid hormones play roles in ovarian carcinogenesis. Gonadotropins, estrogen, and androgen may be causative factors, while gonadotropin-releasing hormone and progesterone may be protective factors in ovarian cancer pathogenesis. Experimental studies have shown that hormonal receptors are expressed in ovarian cancer cells and mediate the growth-stimulatory or growth-inhibitory effects of the hormones on these cells. Hormonal therapeutic agents have been evaluated in several clinical trials. Most of these trials were conducted in patients with recurrent or refractory ovarian cancer, with modest efficacy and few side effects. Better understanding of the mechanisms through which hormones affect cell growth may improve the efficacy of hormonal therapy. Molecular markers that can reliably predict major clinical outcomes should be investigated further in well-designed trials

Utilization and effectiveness of extended-duration thromboprophylaxis after high-risk abdominopelvic cancer surgery.

2016 ◽  
Vol 34 (7_suppl) ◽  
pp. 62-62
Author(s):  
Jason Dennis Wright ◽  
Ling Chen ◽  
Soledad Jorge ◽  
William M. Burke ◽  
Ana Tergas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Molecular Weight ◽  
Endometrial Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Low Molecular Weight Heparin ◽  
Cancer Surgery ◽  
Low Molecular Weight ◽  
Extended Duration ◽  
High Risk Cancer

62 Background: Extended-duration thromboprophylaxis for 4 weeks after discharge has been demonstrated to reduce venous thromboembolic events (VTE) in cancer patients undergoing abdominopelvic surgery and is recommended in national guidelines. We examined the utilization and effectiveness of extended-duration low molecular weight heparin prophylaxis in high-risk cancer patients after surgery. Methods: We analyzed patients with colon, ovarian, and uterine cancer who underwent surgery from 2009-2013 and who were recorded in the MarketScan database. Multivariable models and propensity score analysis with inverse probability of treatment weights were developed to examine uptake and predictors of use of post-discharge low molecular weight heparin (LMWH) use, VTE incidence, and associated adverse events (transfusion, and hemorrhage). Results: A total of 63,280 patients were identified. Use of extended-duration prophylaxis increased from 2009 to 2013 from 1.4% to 1.7% (P = 0.67) for colectomy, 5.9% to 18.3% for ovarian cancer surgery (P < 0.001), and 6.3% to 12.2% (P < 0.001) for hysterectomy for endometrial cancer. There was no association between use of extended-duration prophylaxis and reductions in VTE for any of the procedures: colectomy (2.4% with extended-duration prophylaxis vs. 2.9% without prophylaxis, OR = 0.84; 95% CI, 0.54-1.31), ovarian cancer-directed surgery (3.7% vs. 3.6%, OR = 1.01; 95% CI, 0.76-1.33), hysterectomy (2.1% vs. 2.1%; OR = 0.96; 95% CI, 0.67-1.38). Extended-duration prophylaxis was associated with an increased risk of adverse postoperative events: 2.20 (95% CI, 1.51-3.19) after colectomy, 1.24 (95% CI, 0.92-1.68) following ovarian cancer-directed surgery and 0.99 (95% CI, 0.66-1.48) for hysterectomy for endometrial cancer. Conclusions: Use of extended-duration thromboprophylaxis is low among high-risk cancer patients undergoing surgery. The effectiveness of prophylaxis in real world populations requires further evaluation.

scholarly journals Radiomics in cervical and endometrial cancer

2021 ◽  
pp. 20201314
Author(s):  
Lucia Manganaro ◽  
Gabriele Maria Nicolino ◽  
Miriam Dolciami ◽  
Federica Martorana ◽  
Anastasios Stathis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cervical Cancer ◽  
Developing Countries ◽  
Endometrial Cancer ◽  
Prognostic Factors ◽  
Clinical Decision ◽  
Quantitative Information ◽  
Response To Therapy ◽  
Gynecological Malignancy

Radiomics is an emerging field of research that aims to find associations between quantitative information extracted from imaging examinations and clinical data to support the best clinical decision. In the last few years, some papers have been evaluating the role of radiomics in gynecological malignancies, mainly focusing on ovarian cancer. Nonetheless, cervical cancer is the most frequent gynecological malignancy in developing countries and endometrial cancer is the most common in western countries. The purpose of this narrative review is to give an overview of the latest published papers evaluating the role of radiomics in cervical and endometrial cancer, mostly evaluating association with tumor prognostic factors, with response to therapy and with prediction of recurrence and distant metastasis.

scholarly journals Fertility Sparing Treatments in Endometrial Cancer Patients: The Potential Role of the New Molecular Classification

2021 ◽  
Vol 22 (22) ◽  
pp. 12248
Author(s):  
Anna Franca Cavaliere ◽  
Federica Perelli ◽  
Simona Zaami ◽  
Marco D’Indinosante ◽  
Irene Turrini ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Patients ◽  
Young Patients ◽  
Hormonal Treatment ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Gynecological Malignancy ◽  
Oncological Safety ◽  
Fertility Sparing ◽  
Cancer Genome Atlas

Endometrial cancer is the most frequent gynecological malignancy, and, although epidemiologically it mainly affects advanced age women, it can also affect young patients who want children and who have not yet completed their procreative project. Fertility sparing treatments are the subject of many studies and research in continuous evolution, and represent a light of hope for young cancer patients who find themselves having to face an oncological path before fulfilling their desire for motherhood. The advances in molecular biology and the more precise clinical and prognostic classification of endometrial cancer based on the 2013 The Cancer Genome Atlas classification allow for the selection of patients who can be submitted to fertility sparing treatments with increasing oncological safety. It would also be possible to predict the response to hormonal treatment by investigating the state of the genes of the mismatch repair.

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