scholarly journals Review of Mendelian Randomization Studies on Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jian-Zeng Guo ◽  
Qian Xiao ◽  
Song Gao ◽  
Xiu-Qin Li ◽  
Qi-Jun Wu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ovarian Cancer ◽  
Mendelian Randomization ◽  
Polycystic Ovary ◽  
Epidemiological Studies ◽  
Therapeutic Interventions ◽  
Mr Studies ◽  
Age At Menarche ◽  
Comprehensive Overview ◽  
Increased Risk

Ovarian cancer (OC) is one of the deadliest gynecological cancers worldwide. Previous observational epidemiological studies have revealed associations between modifiable environmental risk factors and OC risk. However, these studies are prone to confounding, measurement error, and reverse causation, undermining robust causal inference. Mendelian randomization (MR) analysis has been established as a reliable method to investigate the causal relationship between risk factors and diseases using genetic variants to proxy modifiable exposures. Over recent years, MR analysis in OC research has received extensive attention, providing valuable insights into the etiology of OC as well as holding promise for identifying potential therapeutic interventions. This review provides a comprehensive overview of the key principles and assumptions of MR analysis. Published MR studies focusing on the causality between different risk factors and OC risk are summarized, along with comprehensive analysis of the method and its future applications. The results of MR studies on OC showed that higher BMI and height, earlier age at menarche, endometriosis, schizophrenia, and higher circulating β-carotene and circulating zinc levels are associated with an increased risk of OC. In contrast, polycystic ovary syndrome; vitiligo; higher circulating vitamin D, magnesium, and testosterone levels; and HMG-CoA reductase inhibition are associated with a reduced risk of OC. MR analysis presents a2 valuable approach to understanding the causality between different risk factors and OC after full consideration of its inherent assumptions and limitations.

scholarly journals Bi-directional Mendelian randomization of epithelial ovarian cancer and schizophrenia and uni-directional Mendelian randomization of schizophrenia on circulating glycerophosphocholine metabolites

2019 ◽  
Author(s):  
Charleen D. Adams ◽  
Susan L. Neuhausen
Keyword(s):  
Risk Factors ◽  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Late Stage ◽  
Mendelian Randomization ◽  
Metabolic Changes ◽  
Choline Metabolism ◽  
Stage Disease ◽  
Increased Risk ◽  
Late Stage Disease

ABSTRACTMost women with epithelial ovarian cancer (EOC) present with late-stage disease. As a result, globally, EOC is responsible for more than 150,000 deaths a year. Thus, a better understanding of risk factors for developing EOC is crucial for earlier screening and detection to improve survival. To that effort, there have been suggestions that there is an association of schizophrenia and cancer, possibly because metabolic changes are a hallmark of both cancer and schizophrenia (SZ). Perturbed choline metabolism has been documented in both diseases. Our objective was to use Mendelian randomization to evaluate whether SZ increased risk for developing EOC or the converse, and, whether SZ impacted glycerophosphocholine (GPC) metabolites. We found that SZ conferred a weak but increased risk for EOC, but not the reverse (no evidence that EOC caused SZ). SZ was also causally associated with lower levels of two GPC species and with suggestively lower levels in an additional three GPCs. We postulate that perturbed choline metabolism in SZ may mimic or contribute to a “cholinic” phenotype, as observed in EOC cells.

Fertility Drugs and Ovarian Cancer

2018 ◽  
Vol 18 (6) ◽  
pp. 567-576 ◽  
Author(s):  
Aus Tariq Ali
Keyword(s):  
Risk Factors ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Health Effects ◽  
Epidemiological Studies ◽  
Fertility Treatment ◽  
Ovarian Cancer Risk ◽  
Fertility Drugs ◽  
Increased Risk

The aetiology of ovarian cancer is multifactorial with both endogenous and exogenous risk factors playing an important role. The exact pathogenesis of ovarian cancer is still not well understood, despite the number of hypotheses published. Due to an increase in the number of women using fertility drugs, much attention has been focused on the long-term health effects of such drugs. Although fertility drugs facilitate the ovulation process, it is however associated with a significant increase in hormone concentrations, placing exposed women at increased risk of gynaecological cancer. Many clinical and epidemiological studies have examined the association between fertility drugs and ovarian cancer risk. Results from these studies have been contradictory, as some studies have reported an increased risk of ovarian cancer while others reported no increased risk. Nevertheless, recent studies have shown that women who used fertility drugs and did not conceive had a higher risk of developing ovarian cancer, compared to women who used fertility drugs and conceived and delivered successfully. This review discusses the effect of fertility drugs on the risk of developing ovarian cancer, providing details on four possible scenarios associated with fertility treatment. In addition, the limitations of previous studies and their impact on our understanding of the association between fertility drugs and ovarian cancer have also been highlighted.

scholarly journals Evaluating the effects of alcohol and tobacco use on cardiovascular disease using multivariable Mendelian randomization

2019 ◽  
Author(s):  
Daniel B. Rosoff ◽  
George Davey Smith ◽  
Nehal Mehta ◽  
Toni-Kim Clarke ◽  
Falk W. Lohoff
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Alcohol Use ◽  
Tobacco Use ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Density Lipoprotein ◽  
Genome Wide Association Studies ◽  
Cvd Risk ◽  
Increased Risk

ABSTRACTAlcohol and tobacco use, two major modifiable risk factors for cardiovascular disease (CVD), are often consumed together. Using large publicly available genome-wide association studies (results from > 940,000 participants), we conducted two-sample multivariable Mendelian randomization (MR) to simultaneously assess the independent effects of alcohol and tobacco use on CVD risk factors and events. We found genetic instruments associated with increased alcohol use, controlling for tobacco use, associated with increased high-density-lipoprotein-cholesterol (HDL-C), decreased triglycerides, but not with coronary heart disease (CHD), myocardial infarction (MI), nor stroke; and instruments for increased tobacco use, controlling for alcohol use, associated with decreased HDL-C, increased triglycerides, and increased risk of CHD and MI. Exploratory analysis found associations with HDL-C, LDL-C, and intermediate-density-lipoprotein metabolites. Consistency of results across complementary methods accommodating different MR assumptions strengthened causal inference, providing strong genetic evidence for the causal effects of modifiable lifestyle risk factors on CVD risk.

scholarly journals COVID-19 Mortality is Associated with Impaired Innate Immunity in Pre-existing Health Conditions

2021 ◽  
Author(s):  
Matthew E Lee ◽  
Yung Chang ◽  
Navid Ahmadinejad ◽  
Crista E Johnson-Agbakwu ◽  
Celeste Bailey ◽  
...  
Keyword(s):  
Risk Factors ◽  
Innate Immunity ◽  
Viral Infections ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Therapeutic Interventions ◽  
Health Conditions ◽  
Molecular Abnormalities ◽  
Hazard Ratios ◽  
Increased Risk

Background: COVID-19 poses a life-threatening endangerment to individuals with chronic diseases. However, not all comorbidities affect COVID-19 prognosis equally. Some increase the risk of COVID-19 related death by more than six folds while others show little to no impact. To prevent severe outcomes, it is critical that we comprehend pre-existing molecular abnormalities in common health conditions that predispose patients to poor prognoses. In this study, we aim to discover some of these molecular risk factors by associating gene expression dysregulations in common health conditions with COVID-19 mortality rates in different cohorts. Methods: We focused on fourteen pre-existing health conditions, for which age-and-sex-adjusted hazard ratios of COVID-19 mortality have been documented. For each health condition, we analyzed existing transcriptomics data to identify differentially expressed genes (DEGs) between affected individuals and unaffected individuals. We then tested if fold changes of any DEG in these pre-existing conditions were correlated with hazard ratios of COVID-19 mortality to discover molecular risk factors. We performed gene set enrichment analysis to identify functional groups overrepresented in these risk factor genes and examined their relationships with the COVID-19 disease pathway. Results: We found that upregulated expression of 70 genes and downregulated expression of 181 genes in pre-existing health conditions were correlated with increased risk of COVID-19 related death. These genes were significantly enriched with endoplasmic reticulum (ER) function, proinflammatory reaction, and interferon production that participate in viral transcription and immune responses to viral infections. Conclusions: Impaired innate immunity in pre-existing health conditions are associated with increased hazard of COVID-19 mortality. The discovered molecular risk factors are potential prognostic biomarkers and targets for therapeutic interventions.

Mendelian Randomization Analysis as a Tool to Gain Insights into Causes of Diseases: A Primer

2021 ◽  
pp. ASN.2020121760
Author(s):  
Adrienne Tin ◽  
Anna Köttgen
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mendelian Randomization ◽  
Mr Studies ◽  
Causal Relationships ◽  
Omics Technologies ◽  
Basic Concepts ◽  
Traditional Risk Factors ◽  
Randomization Analysis

Many Mendelian randomization (MR) studies have recently been published, with inferences on the causal relationships between risk factors and diseases that have potential implications for clinical research. In nephrology, MR methods have been applied to investigate potential causal relationships of traditional risk factors, lifestyle factors, and biomarkers from omics technologies with kidney function or chronic kidney disease. This primer summarizes the basic concepts of MR studies, highlighting methods employed in recent applications, and emphasizes key elements in conducting and reporting of MR studies that are important for interpreting the results.

scholarly journals Appraising the role of previously reported risk factors in epithelial ovarian cancer risk: A Mendelian randomization analysis

PLoS Medicine ◽  
2019 ◽  
Vol 16 (8) ◽  
pp. e1002893 ◽  
Author(s):  
James Yarmolinsky ◽  
Caroline L. Relton ◽  
Artitaya Lophatananon ◽  
Kenneth Muir ◽  
Usha Menon ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Epithelial Ovarian Cancer ◽  
Mendelian Randomization ◽  
Ovarian Cancer Risk ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis

scholarly journals High BMI and Insulin Resistance Are Risk Factors for Spontaneous Abortion in Patients With Polycystic Ovary Syndrome Undergoing Assisted Reproductive Treatment: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Yi-Fei Sun ◽  
Jie Zhang ◽  
Yue-Ming Xu ◽  
Zi-Yu Cao ◽  
Yi-Zhuo Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Spontaneous Abortion ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Abortion Rate ◽  
Ovary Syndrome ◽  
Assisted Reproductive Treatment ◽  
Increased Risk ◽  
High Bmi

BackgroundThe risk of spontaneous abortion in patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive treatment (ART) is higher than that in patients without PCOS, however, no definitive risk factors have been confirmed to associate with the high spontaneous abortion rate in PCOS patients undergoing ART. This study was performed to assess the impact of relevant risk factors on spontaneous abortion in patients with PCOS. Clinical questions were formulated and organized according to the PICOS principle.MethodsA systematic review and meta-analysis were conducted on all published studies on PCOS and spontaneous abortion in Embase, PubMed, Web of Science and Cochrane Library. Related risk factors included body mass index (BMI), age, insulin resistance (IR), hyperandrogenism, and chromosome aberrations. All patients were diagnosed as PCOS using the Rotterdam criteria. The primary endpoint was miscarriage and live birth rate. Fixed-effect models were used to analyze homogeneous data, and subgroup and sensitivity analyses were performed on heterogeneous data. The source of heterogeneity was evaluated, and the random effect model was used to summarize the heterogeneity.ResultsAmong 1836 retrieved articles, 22 were eligible and included in the analysis with 11182 patients. High BMI (OR = 1.48, 95% CI [1.32, 1.67], MD = 1.35, 95% CI [0.58,2.12]) and insulin resistance (MD = 0.32, 95% CI [0.15, 0.49]) were associated with an increased risk of spontaneous abortion in PCOS patients undergoing ART. Older age (OR = 0.29, 95% CI [0.29, 0.44], MD = 2.01, 95% CI [0.04, 4.18]), embryonic chromosomal aberrations (OR = 0.75, 95%CI [0.31,1.77]), and hyperandrogenism (MD = 0.10, 95% CI [- 0.02, 0.22]) were not associated with the high spontaneous abortion rate in patients with PCOS. A subgroup analysis of BMI showed that there was no statistically significant difference in the effect between overweight and obesity on spontaneous abortion in PCOS patients undergoing ART (OR = 1.34, 95% [0.97, 1.85]).ConclusionHigh BMI and insulin resistance are two risk factors for an increased risk of spontaneous abortion in PCOS patients undergoing ART, and losing weight and mitigating insulin resistance may decrease the spontaneous abortion rate in these patients undergoing ART.

Lifestyle and sociodemographic risk factors for gastroschisis: a systematic review and meta-analysis

2020 ◽  
Vol 105 (8) ◽  
pp. 756-764 ◽  
Author(s):  
Silvia Baldacci ◽  
Michele Santoro ◽  
Alessio Coi ◽  
Lorena Mezzasalma ◽  
Fabrizio Bianchi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Illicit Drugs ◽  
Meta Analysis ◽  
Genetic Risk Factors ◽  
Epidemiological Studies ◽  
Black Mothers ◽  
Increased Risk ◽  
Sociodemographic Risk ◽  
Meta Analyses

BackgroundGastroschisis is strongly associated with young maternal age. This association suggests the need for further investigations on non-genetic risk factors. Identifying these risk factors is a public health priority in order to develop prevention strategies aimed at reducing the prevalence and health consequences in offspring.ObjectiveTo systematically assess and quantitatively synthesise the available epidemiological studies to evaluate the association between non-genetic risk factors and gastroschisis.MethodsLiterature from PubMed, EMBASE and Scopus was searched for the period 1990–2018. Epidemiological studies reporting risk estimates between lifestyle and sociodemographic risk factors and gastroschisis were included. Two pairs of reviewers independently extracted information on study characteristics following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and MOOSE (Meta-analysis Of Oservational Studies in Epidemiology) guidelines. Relative risk (RR) estimates were calculated across the studies and meta-analysis was performed using random-effects model.ResultsWe identified 58 studies. Meta-analyses were conducted on 29 studies. Maternal smoking (RR 1.56, 95% CI 1.40 to 1.74), illicit drug use (RR 2.14, 95% CI 1.48 to 3.07) and alcohol consumption (RR 1.40, 95% CI 1.13 to 1.70) were associated with an increased risk of gastroschisis. A decreased risk among black mothers compared with non-Hispanic white mothers (RR 0.49, 95% CI 0.38 to 0.63) was found. For Hispanic mothers no association was observed.ConclusionsExposure to smoking, illicit drugs and alcohol during pregnancy is associated with an increased risk of gastroschisis. A significantly decreased risk for black mothers was observed. Further epidemiological studies to assess the potential role of other environmental factors are strongly recommended.PROSPERO registration numberCRD42018104284.

scholarly journals Endocrine Risk Factors of Endometrial Cancer: Polycystic Ovary Syndrome, Oral Contraceptives, Infertility, Tamoxifen

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1766 ◽  
Author(s):  
Atanas Ignatov ◽  
Olaf Ortmann
Keyword(s):  
Endometrial Cancer ◽  
Polycystic Ovary Syndrome ◽  
Oral Contraceptives ◽  
Polycystic Ovary ◽  
Gynecologic Cancer ◽  
Age At Menarche ◽  
Published Data ◽  
Ovary Syndrome ◽  
Increased Risk

Endometrial cancer is the most common gynecologic cancer and is predominantly endocrine-related. The role of unopposed estrogen in the development of endometrial cancer has been investigated in numerous studies. Different reproductive factors such as younger age at menarche, late age at menopause, infertility, nulliparity, age of birth of the first child, and long-term use of unopposed estrogens during hormone replacement therapy have been associated with an increased risk of endometrial cancer. In contrast, there is a growing body of evidence for a protective role of oral contraceptives. Most of the published data on the association between infertility and polycystic ovary syndrome are inconclusive, whereas the effect of tamoxifen on the risk of endometrial cancer has been well established. With this review, we aim to summarize the evidence on the association between infertility, polycystic ovary syndrome, oral contraceptives, and tamoxifen and the development of endometrial cancer.

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