BRCA1andBRCA2mutations in ovarian cancer patients from China: ethnic-related mutations inBRCA1associated with an increased risk of ovarian cancer

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.

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Colorectal Cancer Risk in Women with Gynecologic Cancers—A Population Retrospective Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm10143127 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3127

Author(s):

Szu-Chia Liao ◽

Hong-Zen Yeh ◽

Chi-Sen Chang ◽

Wei-Chih Chen ◽

Chih-Hsin Muo ◽

...

Keyword(s):

Colorectal Cancer ◽

Ovarian Cancer ◽

Cervical Cancer ◽

Cohort Study ◽

Cancer Patients ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Gynecologic Cancer ◽

Ovarian Cancers ◽

Increased Risk

We conducted a retrospective cohort study to evaluate the subsequent colorectal cancer (CRC) risk for women with gynecologic malignancy using insurance claims data of Taiwan. We identified patients who survived cervical cancer (N = 25,370), endometrial cancer (N = 8149) and ovarian cancer (N = 7933) newly diagnosed from 1998 to 2010, and randomly selected comparisons (N = 165,808) without cancer, matched by age and diagnosis date. By the end of 2011, the incidence and hazard ratio (HR) of CRC were estimated. We found that CRC incidence rates were 1.26-, 2.20-, and 1.61-fold higher in women with cervical, endometrial and ovarian cancers, respectively, than in comparisons (1.09/1000 person–years). The CRC incidence increased with age. Higher adjusted HRs of CRC appeared within 3 years for women with endometrial and ovarian cancers, but not until the 4th to 7th years of follow up for cervical cancer survivals. Cancer treatments could reduce CRC risks, but not significantly. However, ovarian cancer patients receiving surgery alone had an incidence of 3.33/1000 person–years for CRC with an adjusted HR of 3.79 (95% CI 1.11–12.9) compared to patients without any treatment. In conclusion, gynecologic cancer patients are at an increased risk of developing CRC, sooner for those with endometrial or ovarian cancer than those with cervical cancer.

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Phase 1A clinical trial of the first-in-class fascin inhibitor NP-G2-044 evaluating safety and anti-tumor activity in patients with advanced and metastatic solid tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2548 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2548-2548

Author(s):

Vincent Chung ◽

Komal L. Jhaveri ◽

Daniel D. Von Hoff ◽

Xin-Yun Huang ◽

Edward Graeme Garmey ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Trial ◽

Dendritic Cells ◽

Cancer Patients ◽

Checkpoint Inhibitors ◽

Drug Synergism ◽

Duration Of Treatment ◽

Antigen Uptake ◽

Increased Risk ◽

Metastatic Activity

2548 Background: Fascin inhibitors block tumor metastasis and increase antigen uptake in intra-tumoral dendritic cells. Filopodia, finger-like protrusions on cell surfaces, are necessary for migration of metastatic tumor cells and intra-tumoral dendritic cells. Fascin is the primary actin cross-linker in filopodia and elevated levels correlate with increased risk of metastasis, disease progression and mortality. NP-G2-044 is a novel small molecule that inhibits function of fascin. Pre-clinical data demonstrate drug-associated reductions in tumor growth and metastasis, enhanced immune response and survival in treated animals, and drug-drug synergism when combined with anti-PD-1 antibodies. Methods: This multicenter phase 1A clinical trial was designed to evaluate safety and tolerability of NP-G2-044 and to identify the drug’s recommended phase 2 dose (RP2D) using a 3+3 dose escalation design. NP-G2-044 was administered to patients (pts.) with treatment-refractory solid tumor malignancies as a single oral daily dose for 6-week cycles that included 4 weeks on (daily dosing) and 2 weeks off (rest). Results: A total of 23 pts. were enrolled in 7 dose cohorts ranging from 200-2100 mg. QD. Overall, NP-G2-044 appeared well-absorbed and distributed with Tmax of ̃4 hrs and T1/2 of 20-24 hrs. Across all cohorts, no DLTs, drug-related SAEs or patient deaths were observed. Based on PK and safety findings, 1600 mg. daily was selected as the provisional RP2D. While no formal RECIST-based objective responses were observed, consistent with the drug’s non-cytotoxic mechanism of action, preliminary signals of anti-tumor and anti-metastatic activity were observed. These include dose proportional increases in duration of treatment, progression-free-survival, and metastasis-free interval, in particular for 4/4 late-stage ovarian cancer patients (table). Comparison of time on treatment (TOT) for ovarian cancer patients. Conclusions: In this first-in-human clinical trial, the novel fascin inhibitor, NP-G2-044, appeared safe and well tolerated. Signals of single-drug anti-tumor and anti-metastatic activity were observed. A phase 2A clinical trial with a particular focus on Ovarian Cancer will seek to elucidate signals of RP2D activity in both monotherapy and the combination of NP-G2-044 with anti-PD-(L)1 immune checkpoint inhibitors. Clinical trial information: NCT03199586. [Table: see text]

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Identifying Potential Markers for Monitoring Progression to Ovarian Cancer Using Plasma Label-free Proteomics

10.21203/rs.2.19189/v1 ◽

2019 ◽

Author(s):

Wenjie Wang ◽

Hongyu Xie ◽

Bairong Xia ◽

LiuChao Zhang ◽

Ce Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Plasma Protein ◽

Late Stage ◽

Early Stage ◽

Label Free ◽

Absolute Quantitation ◽

Keywords Ovarian Cancer ◽

Benign Ovarian Tumor ◽

Increased Risk

Abstract PurposeCancer antigen 125 (CA125) is considered to have high sensitivity but poor specificity for ovarian cancer. New biomarkers utilized to early detect and monitor the progression of ovarian cancer patients are critically needed. Methods A total of 80 patients including 16 early stage, and matched with 17 late stage, 23 benign ovarian tumor (BOT) and 24 uterine fibroid (UF) patients were utilized to perform plasma proteomics analysis using isobaric tag for relative and absolute quantitation (iTRAQ) method to identify differential diagnostic proteins of ovarian cancer patients. A validation set of 9 early stage, 11 late stage, 17 BOT and 16 UF collected by an independent cohort of samples with the same matching principles was examined to confirm the expressed levels of differential expression proteins by ELISA analysis. Results CRP and ARHGEF 11 were identified as potential diagnostic biomarkers of ovarian cancer. Results of area under the curve (AUC) analysis suggested that combination of diagnostic proteins and CA125 achieved a much higher diagnostic accuracy compared with CA125 alone (AUC values: 0.98 versus 0.80), especially improved the specificity (0.97 versus 0.77). In addition, elevated plasma CRP levels were associated with increased risk of ovarian cancer. Conclusions Current study found that plasma protein CRP was an indicator for monitoring the progression of ovarian cancer. Combination of plasma protein biomarkers with CA125 could be utilized to early diagnose of ovarian cancer patients. Keywords ovarian cancer, proteomics, diagnosis, progression, CRP

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Increased risk of poor survival in ovarian cancer patients with high expression of SNAI2 and lymphovascular space invasion

Oncotarget ◽

10.18632/oncotarget.14192 ◽

2016 ◽

Vol 8 (6) ◽

pp. 9672-9685 ◽

Cited By ~ 4

Author(s):

Jun Li ◽

Shufen Li ◽

Ruifang Chen ◽

Xin Lu

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

High Expression ◽

Poor Survival ◽

Increased Risk ◽

Lymphovascular Space Invasion

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Identification of CHEK2 germline mutations in BRCA1/2 and PALB2 negative breast and ovarian cancer patients

Human Heredity ◽

10.1159/000521369 ◽

2022 ◽

Author(s):

Fuat Aksoy ◽

Havva Tezcan Unlu ◽

Gulsah Cecener ◽

Gamze Guney Eskiler ◽

Unal Egeli ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Patients ◽

Early Onset ◽

Mutational Analysis ◽

Turkish Population ◽

Heteroduplex Analysis ◽

Chek2 Gene ◽

Increased Risk ◽

Wide Range

Introduction: The CHEK2 gene is known to be an important signal transducer involved in DNA repair, apoptosis, or cell cycle arrest in response to DNA damage. The mutations in this gene have been associated with a wide range of cancers, both sporadic and hereditary. Germline CHEK2 mutations are linked to an increased risk of breast cancer. Therefore, the aim of this study was to identify the prevalence of CHEK2 variants in BRCA1/2 and PALB2 negative early-onset patients with breast cancer and/or ovarian cancer in a Turkish population for the first time. Methods: The study included 95 patients with BRCA1/2 and PALB2 negative early-onset breast cancer and/or ovarian cancer and also 60 unaffected women. All the intron/exon boundaries and coding exons of CHEK2 were subjected to mutational analysis by heteroduplex analysis and DNA sequencing. Results: A total of 16 CHEK2 variants were found in breast cancer patients within the Turkish population. CHEK2 c.1100delC mutation studied in the CHEK2 gene most frequently was not detected in our study. The prevalence of variants of uncertain significance in CHEK2 was found to be 7.3% (n= 7) in BRCA1/2 and PALB2 mutation negative Turkish patients with early-onset breast and/or ovarian cancer. Discussion/Conclusion: The present study may shed light on alternative variations that could be significant for understanding the prevalence and clinical suitability of the CHEK2 gene.

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The impact of obesity on treatment and outcomes in ovarian cancer by race/ethnicity.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e18067 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e18067-e18067

Author(s):

Alexandra Martin ◽

Adrianne Rose Mallen ◽

Sweta Sinha ◽

Ali Wells ◽

Kathryn Cline ◽

...

Keyword(s):

Ovarian Cancer ◽

Dose Reduction ◽

Cancer Patients ◽

Tertiary Care ◽

Dose Intensity ◽

Comprehensive Cancer Center ◽

Increased Risk ◽

Race Ethnicity ◽

Similar Survival ◽

The Impact

e18067 Background: Concern for toxicities in obese ovarian cancer patients may limit weight-based chemotherapy dosing, which has been associated with poor survival. We sought to evaluate the impact of obesity on treatment and outcomes by race/ethnicity at a National Cancer Institute (NCI)-designated Comprehensive Cancer Center (CCC). Methods: 66 minority (non-Hispanic black, Hispanic) epithelial ovarian cancer patients diagnosed 2006 and treated with frontline chemotherapy were frequency matched to two non-Hispanic white (NHW) patients by 5-year age group and stage (n = 198). For frontline carboplatin, relative dose intensity (RDI) was calculated by dividing the dose received by the expected dose, with an RDI < 0.85 indicating carboplatin dose reduction. Patient characteristics and RDI were compared by obesity and race/ethnicity. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between obesity, race/ethnicity and RDI with mortality, adjusting for confounders. Results: Minorities were more likely to be obese, underinsured, and to experience delays in chemotherapy compared to NHW. Compared to normal/overweight patients, obese patients were more likely to experience carboplatin under dosing in the neoadjuvant (p = 0.004) and adjuvant (p < 0.0001) setting, but there were no differences in RDI by race/ethnicity or toxicities. No association with survival was observed for dose reduction and BMI. Compared to NHW, minorities had similar survival in the first 4 years after diagnosis (HR = 0.99, 95% CI = 0.60-1.63), but an increased risk of mortality > 4 years after diagnosis (HR = 4.07, 95% CI = 1.92, 8.60). Conclusions: Even though minorities were more likely to be obese, there were no differences in dosing by race/ethnicity at an NCI CCC. Minorities had similar survival to NHW in the first 4 years after diagnosis, likely due to similar access to quality care at an NCI CCC. However, > 4 years after diagnosis, the racial/ethnic survival disparity persisted after adjustment for clinical and pathologic characteristics. Expansion of this work to other patient populations may help determine if findings are similar outside of a tertiary care center.

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Increased risk of brain metastases in ovarian cancer patients with BRCA mutations

Gynecologic Oncology ◽

10.1016/j.ygyno.2019.03.004 ◽

2019 ◽

Vol 153 (3) ◽

pp. 568-573 ◽

Cited By ~ 5

Author(s):

Elena Ratner ◽

Mohan Bala ◽

Melinda Louie-Gao ◽

Ebru Aydin ◽

Sebastien Hazard ◽

...

Keyword(s):

Ovarian Cancer ◽

Brain Metastases ◽

Cancer Patients ◽

Brca Mutations ◽

Increased Risk

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Association of a common variant of SYNPO2 gene with increased risk of serous epithelial ovarian cancer

Tumor Biology ◽

10.1177/1010428317691185 ◽

2017 ◽

Vol 39 (2) ◽

pp. 101042831769118 ◽

Cited By ~ 1

Author(s):

Li Ma ◽

Wei Zhang ◽

Zhaoli Ding ◽

Stephen G Wu ◽

Yaofeng Jin ◽

...

Keyword(s):

Ovarian Cancer ◽

Single Nucleotide Polymorphism ◽

Epithelial Ovarian Cancer ◽

Cancer Patients ◽

Han Chinese ◽

Ovarian Cancer Risk ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Increased Risk ◽

Serous Epithelial Ovarian Cancer

In China, the majority of ovarian cancer patients (80%–90%) are women who are diagnosed with epithelial ovarian cancer. The SYNPO2 gene has recently been reported to be associated with epithelial ovarian cancer in Europeans. To investigate the association of common variants of SYNPO2 gene with epithelial ovarian cancer in Han Chinese individuals, we designed a case–control study with 719 epithelial ovarian cancer patients and 1568 unrelated healthy controls of Han Chinese descent. A total of 49 tagging single-nucleotide polymorphisms were genotyped; single-single-nucleotide polymorphism association, imputation, and haplotypic association analyses were performed. The single-nucleotide polymorphism rs17329882 was found to be strongly associated with serous epithelial ovarian cancer and with ages ≤49 years, consistent with the pre-menopausal status of analyzed epithelial ovarian cancer cases. Odds ratios and 95% confidence intervals provided evidence of the risk effects of the C allele of the single-nucleotide polymorphism on epithelial ovarian cancer. Imputation analyses also confirmed the results with a similar pattern. Additionally, haplotype analyses indicated that the haplotype block that contained rs17329882 was significantly associated with epithelial ovarian cancer risk, specifically with the serous epithelial ovarian cancer subtype. In conclusion, our results show that SYNPO2 gene plays an important role in the etiology of epithelial ovarian cancer, suggesting that this gene may be a potential genetic modifier for developing epithelial ovarian cancer.

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Statin and aspirin use and risk of VTEs in ovarian cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5576 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5576-5576

Author(s):

Hedy S Rennert ◽

Gad Rennert ◽

Ofer Lavie ◽

Shlomi Sagi ◽

Michele Leviov ◽

...

Keyword(s):

Ovarian Cancer ◽

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Cancer Patients ◽

Cox Regression ◽

High Risk Population ◽

Vein Thrombosis ◽

Increased Risk ◽

Venous Thromboembolic Events ◽

Deep Vein

5576 Background: Deep vein thrombosis and pulmonary embolism - venous thromboembolic events (VTEs) - are associated with significant morbidity and increased risk of mortality in cancer patients. Ovarian cancer patients are at a particularly increased risk for VTEs. Statins and aspirin have been shown to reduce the risk of VTEs in the general population in randomized trials. However, the effect of these medications on the incidence of VTEs in ovarian cancer patients has not been studied. Methods: Patients diagnosed with ovarian cancer between years 2000 and 2011 were identified through the Israeli Cancer Registry (ICR). Patients insured by Clalit Health Services, the largest HMO in Israel, were included. Data regarding medication use, chronic diseases and VTE diagnosis were extracted from the computerized database. Patients taking Warfarin or Low Molecular Weight Heparin for 3 months or longer were excluded. Statistical analysis was performed using SPSS (v 18). Use of medications was analyzed as a time dependent covariate in a Cox regression model. Results: Of 1,886 patients 179 (9.5%) had a VTE during a median follow up of 3.13 years. 95 patients (5%) had a VTE 2 years after diagnosis of ovarian cancer. In a multivariate analysis use of chemotherapy and stage 3 or 4 at presentation were associated with an increased risk for VTE's 2 years after diagnosis. Age was associated with a trend for increased risk. Statins were used by 43.2% of the patients, and 31.9% used aspirin. Aspirin use was associated with a reduced incidence of a VTE, which was borderline statistically significant (p=0.054). Statin use did not affect the incidence of VTE's in the group of ovarian carcinoma patients. Conclusions: Our results suggest that in patients with ovarian cancer aspirin use is a possible protector from deep vein thrombosis and pulmonary embolism. Prospective trials are warranted to assess the benefit of aspirin and statins for prevention of VTE's in the high risk population of ovarian cancer patients. [Table: see text]

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