scholarly journals Male origin microchimerism and ovarian cancer

2020 ◽  
Author(s):  
Sara Hallum ◽  
Marianne Antonius Jakobsen ◽  
Thomas Alexander Gerds ◽  
Anja Pinborg ◽  
Anne Tjønneland ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Hormone Replacement ◽  
Ovarian Cancer Risk ◽  
Endogenous Hormones ◽  
Blood Samples ◽  
Hazard Ratios ◽  
Hormonal Exposures ◽  
Underlying Mechanisms ◽  
First Time

Abstract Background Reduced risk of ovarian cancer is commonly ascribed to reduced exposure to endogenous hormones during pregnancy, using oral contraceptives or not using hormone replacement therapy. However, exposure to hormones alone account for less than half of all cases. Many women carry small amounts of male cells—known as male origin microchimerism—in their circulation and remarkable impacts of these cells on women’s health are being published. Here, we pursue the possibility that male origin microchimerism has a role in reducing ovarian cancer risk. Methods We conducted a prospective case-cohort study using blood samples and questionnaire data from 700 women participating in the Danish Diet, Cancer, and Health cohort. Blood samples were analysed for Y chromosome presence as a marker of male microchimerism. We evaluated the association between male microchimerism and ovarian cancer, using weighted Cox regression models reporting hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Results Male microchimerism was detected in 46% of cases and 65.9% of controls. Women testing positive for male microchimerism had a reduced hazard rate of ovarian cancer compared with women testing negative (HR = 0.44, 95% CI: 0.29-0.68). We found no evidence of interaction with measures of hormonal exposures (P = 0.50). Conclusions For the first time we report that women who test positive for male microchimerism in their circulation have reduced rates of ovarian cancer compared with women who test negative. Although the underlying mechanisms are presently unknown, we believe male microchimerism is potent in preventing ovarian cancer.

The influence of reproductive and hormonal factors on ovarian cancer survival

2008 ◽  
Vol 18 (3) ◽  
pp. 407-413 ◽  
Author(s):  
C. M. Nagle ◽  
C. J. Bain ◽  
A. C. Green ◽  
P. M. Webb
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Cancer Survival ◽  
Cox Regression ◽  
Population Based ◽  
Hazard Ratios ◽  
History Of ◽  
Hormonal Exposures ◽  
Ovarian Cancer Survival ◽  
Invasive Epithelial Ovarian Cancer

Reproductive and hormonal exposures are known to influence ovarian carcinogenesis, but little is known about the effect of these factors on survival. We have studied survival according to hormonal and reproductive history in a population-based cohort of 676 Australian women aged 18–79, newly diagnosed with invasive epithelial ovarian cancer in the early 1990s. In order to place our findings in context, we have also undertaken a systematic review of the pertinent literature. Detailed information about each woman's reproductive and contraceptive history was obtained from pregnancy and contraceptive calendars at the time of diagnosis. Cox regression was used to obtain multivariate adjusted hazard ratios (HR) and 95% confidence intervals (CI). A total of 419 (62%) of the 676 women died during the follow-up (giving a 5-year survival proportion of 44%). Apart from better survival for women who had ever breastfed (multivariate HR 0.74, 95% CI 0.55–0.98), we found no association between survival from invasive ovarian cancer and a range of hormonal and gynecological factors including parity, use of oral contraceptives, and histories of tubal sterilization or hysterectomy. Systematic review of the literature generally supported the lack of influence of these factors on survival from ovarian cancer. We conclude that, except for a possible survival advantage among women with a history of breastfeeding, reproductive and hormonal exposures prior to diagnosis do not influence survival from invasive ovarian cancer, in contrast to their substantial effects on etiology of this disease

scholarly journals The Association Between Hysterectomy and Ovarian Cancer Risk: A Population-Based Record-Linkage Study

2019 ◽  
Vol 111 (10) ◽  
pp. 1097-1103
Author(s):  
Suzanne C Dixon-Suen ◽  
Penelope M Webb ◽  
Louise F Wilson ◽  
Karen Tuesley ◽  
Louise M Stewart ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Risk ◽  
Record Linkage ◽  
Cox Regression ◽  
Population Based ◽  
Linkage Study ◽  
Ovarian Cancer Risk ◽  
Hazard Ratios ◽  
Time Period ◽  
Hospital Births

Abstract Background Recent studies have called into question the long-held belief that hysterectomy without oophorectomy protects against ovarian cancer. This population-based longitudinal record-linkage study aimed to explore this relationship, overall and by age at hysterectomy, time period, surgery type, and indication for hysterectomy. Methods We followed the female adult Western Australian population (837 942 women) across a 27-year period using linked electoral, hospital, births, deaths, and cancer records. Surgery dates were determined from hospital records, and ovarian cancer diagnoses (n = 1640) were ascertained from cancer registry records. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between hysterectomy and ovarian cancer incidence. Results Hysterectomy without oophorectomy (n = 78 594) was not associated with risk of invasive ovarian cancer overall (HR = 0.98, 95% CI = 0.85 to 1.11) or with the most common serous subtype (HR = 1.05, 95% CI = 0.89 to 1.23). Estimates did not vary statistically significantly by age at procedure, time period, or surgical approach. However, among women with endometriosis (5.8%) or with fibroids (5.7%), hysterectomy was associated with substantially decreased ovarian cancer risk overall (HR = 0.17, 95% CI = 0.12 to 0.24, and HR = 0.27, 95% CI = 0.20 to 0.36, respectively) and across all subtypes. Conclusions Our results suggest that for most women, having a hysterectomy with ovarian conservation is not likely to substantially alter their risk of developing ovarian cancer. However, our results, if confirmed, suggest that ovarian cancer risk reduction could be considered as a possible benefit of hysterectomy when making decisions about surgical management of endometriosis or fibroids.

scholarly journals Plasma Vitamin B12 Levels, High-Dose Vitamin B12 Treatment, and Risk of Dementia

2021 ◽  
Vol 79 (4) ◽  
pp. 1601-1612
Author(s):  
Johan Frederik Håkonsen Arendt ◽  
Erzsébet Horváth-Puhó ◽  
Henrik Toft Sørensen ◽  
Ebba Nexø ◽  
Lars Pedersen ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Vascular Dementia ◽  
Cox Regression ◽  
Population Based ◽  
High Dose ◽  
Plasma Vitamin ◽  
Hazard Ratios ◽  
B12 Deficiency ◽  
First Time

Background: It is controversial whether B12 deficiency causes dementia or B12 treatment can prevent dementia. Objective: To assess associations between low plasma (P-)B12 levels, B12 treatment, and risk of Alzheimer’s disease (AD; primary outcome) and all-cause or vascular dementia (secondary outcomes). Methods: We conducted a population-based cohort study using Danish registry data to assess associations between low P-B12 levels, high-dose injection or oral B12 treatment, and risk of dementia (study period 2000–2013). The primary P-B12 cohort included patients with a first-time P-B12 measurement whose subsequent B12 treatment was recorded. The secondary B12 treatment cohort included patients with a first-time B12 prescription and P-B12 measurement within one year before this prescription. For both cohorts, patients with low P-B12 levels (<200 pmol/L) were propensity score-matched 1:1 with patients with normal levels (200–600 pmol/L). We used multivariable Cox regression to compute 0–15-year hazard ratios for dementia. Results: For low P-B12 and normal P-B12 level groups, we included 53,089 patients in the primary P-B12 cohort and 13,656 patients in the secondary B12 treatment cohort. In the P-B12 cohort, hazard ratios for AD centered around one, regardless of follow-up period or treatment during follow-up. In the B12 treatment cohort, risk of AD was unaffected by low pre-treatment P-B12 levels, follow-up period and type of B12 treatment. Findings were similar for all-cause and vascular dementia. Conclusion: We found no associatio1n between low P-B12 levels and dementia. Associations were unaffected by B12 treatment. Results do not support routine screening for B12 deficiency in patients with suspected dementia.

scholarly journals Intake of specific carotenoids and the risk of epithelial ovarian cancer

2007 ◽  
Vol 98 (1) ◽  
pp. 187-193 ◽  
Author(s):  
Min Zhang ◽  
C. D'Arcy J. Holman ◽  
Colin W. Binns
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Contraceptive Use ◽  
Hormone Replacement ◽  
Menopausal Status ◽  
Ovarian Cancer Risk ◽  
Total Carotenoids ◽  
Oral Contraceptive Use ◽  
Tea Drinking ◽  
Β Carotene

There has been considerable interest in the role of carotenoids in the chemoprevention of cancer. However, few studies have examined the association between intake of specific carotenoids and the risk of epithelial ovarian cancer and the results for carotenoids have been inconclusive. To investigate whether the intake of α-carotene, β-carotene, β-cryptoxanthin, lutein and zeaxanthin, and lycopene is inversely associated with ovarian cancer risk, a case–control study was conducted in China during 1999–2000. The cases were 254 patients with histologically confirmed epithelial ovarian cancer and 652 age-matched controls were randomly recruited during the same period. Habitual dietary intake and lifestyle were collected by face-to-face interview using a validated and reliable FFQ. The US Department of Agriculture nutrient composition database was used to calculate the intake of specific carotenoids. Unconditional logistic regression analyses were used to estimate OR and 95 % CI, accounting for age, locality, education, BMI, smoking, tea drinking, parity, oral contraceptive use, hormone replacement therapy, menopausal status, family history of ovarian cancer, physical activity and energy intake. Compared with the highest v. the lowest quartile of intake, the adjusted OR were 0·39 (95 % CI 0·23, 0·66) for α-carotene, 0·51 (95 % CI 0·31, 0·84) for β-carotene, 0·51 (95 % CI 0·31, 0·83) for β-cryptoxanthin, 0·45 (0·27, 0·76) for lutein and zeaxanthin, and 0·33 (95 % CI 0·20, 0·56) for total carotenoids, with statistically significant tests for trend. It is concluded that a higher intake of carotenoids can reduce the risk of epithelial ovarian cancer.

Impact of Male Origin Microchimerism on Cardiovascular Disease in Women: A Prospective Cohort Study

2020 ◽  
Author(s):  
Sara Hallum ◽  
Thomas Alexander Gerds ◽  
Thomas Steen Gyldenstierne Sehested ◽  
Marianne Antonius Jakobsen ◽  
Anne Tjønneland ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cardiovascular Health ◽  
Cox Regression ◽  
Biological Responses ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Cardiovascular Disease In Women ◽  
Underlying Mechanisms ◽  
Reduced Rate ◽  
Unknown Male

Abstract Increasing parity is associated with an increased risk of ischemic heart disease (IHD) and stroke in women. This is likely attributed to biological responses of pregnancy. Male cells of presumed fetal origin are commonly present in women years after pregnancy—a phenomenon termed male origin microchimerism. Here, we investigated whether male origin microchimerism was associated with risk of IHD and ischemic stroke in women. We evaluated the association between male origin microchimerism and ischemic events in a cohort of 766 Danish women enrolled in the Diet, Cancer and Health cohort during 1993–1997 when aged 50–64 years. Of these, 545 (71.2%) tested positive for male origin microchimerism by targeting the Y-chromosome (DYS14) in women’s blood. Multiple Cox regression models were used to report hazard ratios with 95% confidence intervals. We found male origin microchimerism was associated with a significantly reduced rate of IHD (HR=0.44, 95% CI: 0.23, 0.83), but not ischemic stroke (HR=0.80, 95% CI: 0.46, 1.41). Our findings show that microchimerism-positivity is associated with a lower rate of later IHD development in women. Although the underlying mechanisms are presently unknown, male origin microchimerism may be relevant in women’s cardiovascular health. More studies are needed to confirm these findings.

Effect of BRCA Mutations on the Length of Survival in Epithelial Ovarian Tumors

2002 ◽  
Vol 20 (2) ◽  
pp. 463-466 ◽  
Author(s):  
Y. Ben David ◽  
A. Chetrit ◽  
G. Hirsh-Yechezkel ◽  
E. Friedman ◽  
B.D. Beck ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Survival ◽  
Cox Regression ◽  
Ovarian Tumors ◽  
Early Years ◽  
Rank Test ◽  
Brca Mutations ◽  
Blood Samples ◽  
Cox Regression Analysis ◽  
Significant Difference

PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v 37.8 months; 3-year survival, 65.8% v 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.

scholarly journals Ovarian Cancer Risk Scores Based on Immune-Related Pseudogenes to Predict Overall Survival and Guide Immunotherapy and Chemotherapy

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jie Zhao ◽  
Rixiang Zhao ◽  
Xiaocen Wei ◽  
Xiaojing Jiang ◽  
Fan Su
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Cox Regression ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Ovarian Cancer Risk ◽  
Cox Regression Analysis ◽  
The Impact

Background. Ovarian cancer (OC) is the top of the aggressive malignancies in females with a poor survival rate. However, the roles of immune-related pseudogenes (irPseus) in the immune infiltration of OC and the impact on overall survival (OS) have not been adequately studied. Therefore, this study aims to identify a novel model constructed by irPseus to predict OS in OC and to determine its significance in immunotherapy and chemotherapy. Methods. In this study, with the use of The Cancer Genome Atlas (TCGA) combined with Genotype-Tissue Expression (GTEx), 55 differentially expressed irPseus (DEirPseus) were identified. Then, we constructed 10 irPseus pairs with the help of univariate, Lasso, and multivariate Cox regression analysis. The prognostic performance of the model was determined and measured by the Kaplan–Meier curve, a time-dependent receiver operating characteristic (ROC) curve. Results. After dividing OC subjects into high- and low-risk subgroups via the cut-off point, it was revealed that subjects in the high-risk group had a shorter OS. The multivariate Cox regression performed between the model and multiple clinicopathological variables revealed that the model could effectively and independently predict the prognosis of OC. The prognostic model characterized infiltration by various kinds of immune cells and demonstrated the immunotherapy response of subjects with cytotoxic lymphocyte antigen 4 (CTLA4), anti-programmed death-1 (PD-1), and anti-PD-ligand 1 (PD-L1) therapy. A high risk score was related to a higher inhibitory concentration (IC50) for etoposide ( P = 0.0099 ) and mitomycin C ( P = 0.0013 ). Conclusion. It was the first study to identify a novel signature developed by DEirPseus pairs and verify the role in predicting OS, immune infiltrates, immunotherapy, and chemosensitivity. The irPseus are vital factors predicting the prognosis of OC and could act as a novel potential treatment target.

scholarly journals Increased risk of ovarian cancer in integrin β3 Leu33Pro homozygotes

2005 ◽  
Vol 12 (4) ◽  
pp. 945-952 ◽  
Author(s):  
S E Bojesen ◽  
S K Kjær ◽  
E V S Høgdall ◽  
B L Thomsen ◽  
C K Høgdall ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Prospective Study ◽  
Case Control Study ◽  
Cox Regression ◽  
Conditional Logistic Regression ◽  
Case Control ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
Control Study

We previously demonstrated that integrin β3 Leu33Pro homozygotes have an increased risk of cancer, possibly most pronounced for ovarian cancer. We now test the latter hypothesis in case-control and prospective studies. We genotyped 463 Danish women with ovarian cancer, and 4291 women from the Danish general population. Calculation of odds ratios by conditional logistic regression was performed in the case-control study (n=463 + 3543), and of ovarian cancer incidence, log-rank statistics and hazard ratios by Cox regression in the prospective study (n=4291) with 9.5-year follow-up. In the case-control study matched for age and marital status, the odds ratio for ovarian cancer in homozygotes versus non-carriers was 1.6 (95% confidence interval: 1.0–2.6). In the prospective study with 28 incident ovarian cancers, non-carriers and homozygotes had incidences of 7 (4–11) and 30 (10–92) per 10 000 person-years (log-rank P=0.02). The age-adjusted hazard ratio for ovarian cancer in homozygotes versus non-carriers was 3.9 (1.1–13). Risk of ovarian cancer did not differ between heterozygotes and non-carriers in either study. Integrin β3 Leu33Pro homozygotes have an increased risk of ovarian cancer.

scholarly journals Risk reduction strategies for BRCA1/2 hereditary ovarian cancer syndromes: a clinical practice guideline

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Michelle Jacobson ◽  
Nadia Coakley ◽  
Marcus Bernardini ◽  
Kelly-Ann Branco ◽  
Laurie Elit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Risk Reduction ◽  
Hormone Replacement ◽  
Breast Cancer Mortality ◽  
Pathogenic Variant ◽  
Ovarian Cancer Risk ◽  
Eligibility Criteria ◽  
Cancer Risk Reduction

Abstract Objective The purpose of this guideline is to make recommendations regarding the care of women who harbour a pathogenic or likely pathogenic variant in BRCA1 and BRCA2. Methods Draft recommendations were formulated based on evidence obtained through a systematic review of RCTs, comparative retrospective studies and guideline endorsement. The draft recommendations underwent an internal review by clinical and methodology experts, and an external review by clinical practitioners. Results The literature search yielded 1 guideline, 5 systematic reviews, and 15 studies that met the eligibility criteria. Conclusions In women who harbour a pathogenic or likely pathogenic variant in BRCA1 and BRCA2 screening for ovarian cancer is not recommended. Risk-reducing surgery is recommended to reduce the risk of ovarian cancer. In the absence of contraindications, premenopausal women undergoing RRSO should be offered hormone therapy until menopause. Systemic hormone replacement therapy, is not recommended for women who have had a personal history of breast cancer. RRSO should be considered for breast cancer risk reduction in women younger than 50 years. After a breast cancer diagnosis, RRSO for breast cancer mortality reduction can be considered within two years to women who harbour a pathogenic or likely pathogenic variant in BRCA1 if younger than the recommended age range for ovarian cancer risk reduction. RRSO before the age of 40 and specifically for breast cancer treatment in BRCA2 should be considered only if recommended by their breast cancer oncologist. Following RRSO, it is not recommended to do surveillance for peritoneal cancer.

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