scholarly journals Mechanistic and clinical insights at the scleroderma-cancer interface

2017 ◽  
Vol 2 (3) ◽  
pp. 153-159 ◽  
Author(s):  
Ami A. Shah ◽  
Livia Casciola-Rosen
Keyword(s):  
Chronic Inflammation ◽  
Malignant Transformation ◽  
Clinical Implications ◽  
Increased Risk ◽  
Risk Of Cancer

Emerging data suggest tantalizing links between cancer and systemic inflammatory rheumatic syndromes. In scleroderma, patients may have an increased risk of cancer, secondary to chronic inflammation and damage from the disease, malignant transformation promoted by immunosuppressive therapies, a shared susceptibility to both cancer and autoimmunity, or a common inciting exposure. However, it is increasingly recognized that a subset of patients develop cancer around the time that scleroderma clinically manifests, raising the question of cancer-induced autoimmunity. In this review, we discuss data suggesting a mechanistic link between cancer and the development of scleroderma, and the clinical implications of these findings.

scholarly journals Review: Diabetes, Obesity, and Cancer—Pathophysiology and Clinical Implications

2019 ◽  
Vol 41 (1) ◽  
pp. 33-52 ◽  
Author(s):  
Iliana C Lega ◽  
Lorraine L Lipscombe
Keyword(s):  
Clinical Care ◽  
Clinical Implications ◽  
Breast Cancers ◽  
Obesity And Diabetes ◽  
Increased Risk ◽  
Bidirectional Relationship ◽  
The Face ◽  
Obesity And Cancer ◽  
Risk Of Cancer ◽  
Shared Risk

Abstract Obesity and diabetes have both been associated with an increased risk of cancer. In the face of increasing obesity and diabetes rates worldwide, this is a worrying trend for cancer rates. Factors such as hyperinsulinemia, chronic inflammation, antihyperglycemic medications, and shared risk factors have all been identified as potential mechanisms underlying the relationship. The most common obesity- and diabetes-related cancers are endometrial, colorectal, and postmenopausal breast cancers. In this review, we summarize the existing evidence that describes the complex relationship between obesity, diabetes, and cancer, focusing on epidemiological and pathophysiological evidence, and also reviewing the role of antihyperglycemic agents, novel research approaches such as Mendelian Randomization, and the methodological limitations of existing research. In addition, we also describe the bidirectional relationship between diabetes and cancer with a review of the evidence summarizing the risk of diabetes following cancer treatment. We conclude this review by providing clinical implications that are relevant for caring for patients with obesity, diabetes, and cancer and provide recommendations for improving both clinical care and research for patients with these conditions.

scholarly journals Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation

2021 ◽  
Vol 9 ◽  
Author(s):  
Chris M. Li ◽  
Zhibin Chen
Keyword(s):  
Autoimmune Diseases ◽  
Chronic Inflammation ◽  
Cancer Incidence ◽  
Immune Therapy ◽  
Large Body ◽  
Interleukin 4 ◽  
Specific Cell ◽  
Increased Risk ◽  
Risk Of Cancer

Recent epidemiological studies have found an alarming trend of increased cancer incidence in adults younger than 50 years of age and projected a substantial rise in cancer incidence over the next 10 years in this age group. This trend was exemplified in the incidence of non-cardia gastric cancer and its disproportionate impact on non-Hispanic white females under the age of 50. The trend is concurrent with the increasing incidence of autoimmune diseases in industrialized countries, suggesting a causal link between the two. While autoimmunity has been suspected to be a risk factor for some cancers, the exact mechanisms underlying the connection between autoimmunity and cancer remain unclear and are often controversial. The link has been attributed to several mediators such as immune suppression, infection, diet, environment, or, perhaps most plausibly, chronic inflammation because of its well-recognized role in tumorigenesis. In that regard, autoimmune conditions are common causes of chronic inflammation and may trigger repetitive cycles of antigen-specific cell damage, tissue regeneration, and wound healing. Illustrating the connection between autoimmune diseases and cancer are patients who have an increased risk of cancer development associated with genetically predisposed insufficiency of cytotoxic T lymphocyte-associated protein 4 (CTLA4), a prototypical immune checkpoint against autoimmunity and one of the main targets of cancer immune therapy. The tumorigenic process triggered by CTLA4 insufficiency has been shown in a mouse model to be dependent on the type 2 cytokines interleukin-4 (IL4) and interleukin-13 (IL13). In this type 2 inflammatory milieu, crosstalk with type 2 immune cells may initiate epigenetic reprogramming of epithelial cells, leading to a metaplastic differentiation and eventually malignant transformation even in the absence of classical oncogenic mutations. Those findings complement a large body of evidence for type 1, type 3, or other inflammatory mediators in inflammatory tumorigenesis. This review addresses the potential of autoimmunity as a causal factor for tumorigenesis, the underlying inflammatory mechanisms that may vary depending on host-environment variations, and implications to cancer prevention and immunotherapy.

Neuroradiology Manifestations of Li-Fraumeni Syndrome: Epidemiology, Genetics, Imaging Findings, and Management

Neurographics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 228-235
Author(s):  
S. Naganawa ◽  
T. Donohue ◽  
A. Capizzano ◽  
Y. Ota ◽  
J. Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Soft Tissue Sarcomas ◽  
Suppressor Gene ◽  
Imaging Findings ◽  
Li Fraumeni Syndrome ◽  
Increased Risk ◽  
Li Fraumeni ◽  
Risk Of Cancer

Li-Fraumeni syndrome is a familial cancer predisposition syndrome associated with germline mutation of the tumor suppressor gene 53, which encodes the tumor suppressor p53 protein. Affected patients are predisposed to an increased risk of cancer development, including soft-tissue sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma, among other malignancies. The tumor suppressor gene TP53 plays an important, complex role in regulating the cell cycle, collaborating with transcription factors and other proteins. The disruption of appropriate cell cycle regulation by mutated TP53 is considered to be the cause of tumorigenesis in Li-Fraumeni syndrome. Appropriate surveillance, predominantly by using MR imaging, is used for early malignancy screening in an effort to improve the survival rate among individuals who are affected. Patients with Li-Fraumeni syndrome are also at increased risk for neoplasm development after radiation exposure, and, therefore, avoiding unnecessary radiation in both the diagnostic and therapeutic settings is paramount. Here, we review the epidemiology, genetics, imaging findings, and the current standard surveillance protocol for Li-Fraumeni syndrome from the National Comprehensive Cancer Network as well as potential treatment options.Learning Objective: Describe the cause of second primary malignancy among patients with Li-Fraumeni syndrome.

scholarly journals Exploring the Epidemiology of Cancer after Solid Organ Transplantation (EpCOT): an observational cohort study

BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e043731
Author(s):  
Adnan Sharif ◽  
Javeria Peracha ◽  
David Winter ◽  
Raoul Reulen ◽  
Mike Hawkins
Keyword(s):  
Organ Transplantation ◽  
Record Linkage ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Study Cohort ◽  
Solid Organ ◽  
Post Transplantation ◽  
Increased Risk ◽  
Risk Of Cancer

IntroductionSolid organ transplant patients are counselled regarding increased risk of cancer (principally due to their need for lifelong immunosuppression) and it ranks as one of their biggest self-reported worries. Post-transplantation cancer is common, associated with increased healthcare costs and emerging as a leading cause of post-transplant mortality. However, epidemiology of cancer post-transplantation remains poorly understood, with limitations including translating data from different countries and national data being siloed across different registries and/or data warehouses.Methods and analysisStudy methodology for Epidemiology of Cancer after Solid Organ Transplantation involves record linkage between the UK Transplant Registry (from NHS Blood and Transplant), Hospital Episode Statistics (for secondary care episodes from NHS Digital), National Cancer Registry (from cancer registration data hosted by Public Health England) and the National Death Registry (from NHS Digital). Deterministic record linkage will be conducted by NHS Digital, with a fully anonymised linked dataset available for analysis by the research team. The study cohort will consist of up to 85 410 solid organ transplant recipients,who underwent a solid organ transplant in England between 1 January 1985 and 31 December 2015, with up-to-date outcome data.Ethics and disseminationThis study has been approved by the Confidentiality Advisory Group (reference: 16/CAG/0121), Research Ethics Committee (reference: 15/YH/0320) and Institutional Review Board (reference: RRK5471). The results of this study will be presented at national and international conferences, and manuscripts with results will be submitted for publication in high-impact peer-reviewed journals. The information produced will also be used to develop national evidence-based clinical guidelines to inform risk stratification to enable risk-based clinical follow-up.Trial registration numberNCT02991105.

scholarly journals Antihypertensive Drugs and the Risk of Cancer: A Nationwide Cohort Study

2021 ◽  
Vol 10 (4) ◽  
pp. 771
Author(s):  
In-Jeong Cho ◽  
Jeong-Hun Shin ◽  
Mi-Hyang Jung ◽  
Chae Young Kang ◽  
Jinseub Hwang ◽  
...  
Keyword(s):  
Antihypertensive Drugs ◽  
Beta Blockers ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Channel Blockers ◽  
Antihypertensive Medications ◽  
Converting Enzyme Inhibitors ◽  
Incident Cancer ◽  
Increased Risk ◽  
Risk Of Cancer

We sought to assess the association between common antihypertensive drugs and the risk of incident cancer in treated hypertensive patients. Using the Korean National Health Insurance Service database, the risk of cancer incidence was analyzed in patients with hypertension who were initially free of cancer and used the following antihypertensive drug classes: Angiotensin-converting enzyme inhibitors (ACEIs); angiotensin receptor blockers (ARBs); beta blockers (BBs); calcium channel blockers (CCBs); and diuretics. During a median follow-up of 8.6 years, there were 4513 (6.4%) overall cancer incidences from an initial 70,549 individuals taking antihypertensive drugs. ARB use was associated with a decreased risk for overall cancer in a crude model (hazard ratio (HR): 0.744, 95% confidence interval (CI): 0.696–0.794) and a fully adjusted model (HR: 0.833, 95% CI: 0.775–0.896) compared with individuals not taking ARBs. Other antihypertensive drugs, including ACEIs, CCBs, BBs, and diuretics, did not show significant associations with incident cancer overall. The long-term use of ARBs was significantly associated with a reduced risk of incident cancer over time. The users of common antihypertensive medications were not associated with an increased risk of cancer overall compared to users of other classes of antihypertensive drugs. ARB use was independently associated with a decreased risk of cancer overall compared to other antihypertensive drugs.

scholarly journals The association between XRCC3 rs1799794 polymorphism and cancer risk: a meta-analysis of 34 case–control studies

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Weiqing Liu ◽  
Shumin Ma ◽  
Lei Liang ◽  
Zhiyong Kou ◽  
Hongbin Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Thyroid Cancer ◽  
Cancer Risk ◽  
Large Scale ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Cancer Type ◽  
Increased Risk ◽  
Risk Of Cancer

Abstract Background Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer. Methods PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis. Results XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG + AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00–1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00–1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population. Conclusion This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.

scholarly journals Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Molecularly Classified Endometrial Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3124
Author(s):  
Mikko Loukovaara ◽  
Annukka Pasanen ◽  
Ralf Bützow
Keyword(s):  
Risk Factors ◽  
Mismatch Repair ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Molecular Profile ◽  
New Therapeutic Approaches ◽  
Increased Risk ◽  
Mmr Deficiency ◽  
Endometrial Carcinomas ◽  
Risk Of Cancer

The aggressiveness of mismatch repair (MMR) deficient endometrial carcinomas was examined in a single institution retrospective study. Outcomes were similar for MMR proficient (n = 508) and deficient (n = 287) carcinomas, identified by immunohistochemistry. In accordance with molecular classification based on The Cancer Genome Atlas (TCGA), tumors with abnormal p53 staining or polymerase-ϵ exonuclease domain mutation were excluded from the MMR proficient subgroup, termed as “no specific molecular profile” (NSMP). Compared with NSMP (n = 218), MMR deficiency (n = 191) was associated with poor disease-specific survival (p = 0.001). MMR deficiency was associated with an increased risk of cancer-related death when controlling for confounders (hazard ratio 2.0). In the absence of established clinicopathologic risk factors, MMR deficiency was invariably associated with an increased risk of cancer-related death in univariable analyses (hazard ratios ≥ 2.0). In contrast, outcomes for MMR deficient and NSMP subgroups did not differ when risk factors were present. Lymphatic dissemination was more common (p = 0.008) and the proportion of pelvic relapses was higher (p = 0.029) in the MMR deficient subgroup. Our findings emphasize the need for improved triage to adjuvant therapy and new therapeutic approaches in MMR deficient endometrial carcinomas.

scholarly journals Pediatric Cancer Genetics Research and an Evolving Preventive Ethics Approach for Return of Results after Death of the Subject

2015 ◽  
Vol 43 (3) ◽  
pp. 529-537
Author(s):  
Sarah Scollon ◽  
Katie Bergstrom ◽  
Laurence B. McCullough ◽  
Amy L. McGuire ◽  
Stephanie Gutierrez ◽  
...  
Keyword(s):  
Cancer Genetics ◽  
Recurrence Risk ◽  
Genomic Research ◽  
Return Of Results ◽  
Genetics Research ◽  
Personal Significance ◽  
Pediatric Diseases ◽  
Increased Risk ◽  
Preventive Ethics ◽  
Risk Of Cancer

In the pediatric clinical setting, the parent/guardian will almost always be the authorized representative and designated recipient of clinical and research results, making the issue of to whom results should be returned in the pediatric setting less complex than in adult settings. It is also clear that, in genomic research related to pediatric diseases such as cancer, results may be of considerable clinical, ethical, and personal significance for parents in a number of ways, including a genomic explanation of the origin of their child’s cancer, implications for the genetic testing and medical care of other siblings and of the parents themselves, and reproductive planning with regard to the recurrence risk for future children to have an increased risk of cancer. However, what remains unclear is which results should be disclosed, and under what circumstances, to parents of deceased children.

scholarly journals Anti-seizure medication is not associated with an increased risk to develop cancer in epilepsy patients

2021 ◽  
Author(s):  
Jenny Stritzelberger ◽  
Johannes D. Lang ◽  
Tamara M. Mueller ◽  
Caroline Reindl ◽  
Vivien Westermayer ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Cancer Diagnosis ◽  
Index Date ◽  
Control Group ◽  
Protective Effects ◽  
Promoting Effect ◽  
Increased Risk ◽  
Comorbidity Index ◽  
Preclinical And Clinical Studies ◽  
Risk Of Cancer

Abstract Objective Whether anti-seizure medication (ASM) increases the risk for cancer has been debated for decades. While for some ASM, a carcinoma-promoting effect has been suspected, carcinoma-protective effects have been shown for other ASM. However, the issue remains unresolved as data from preclinical and clinical studies have been inconsistent and contradictory. Methods We collected anonymous patient data from practice neurologists throughout Germany between 2009 and 2018 using the IMS Disease Analyzer database (QuintilesIMS, Frankfurt, Germany). People with epilepsy (PWE) with an initial cancer diagnosis and antiepileptic therapy prior to the index date were 1:1 matched with a control group of PWE without cancer according to age, gender, index year, Charlson Comorbidity Index, and treating physician. For both groups, the risk to develop cancer under treatment with different ASMs was analyzed using three different models (ever use vs. never use (I), effect per one (II) and per five therapy years (III). Results A total of 3152 PWE were included (each group, n = 1,576; age = 67.3 ± 14.0 years). The risk to develop cancer was not significantly elevated for any ASM. Carbamazepine was associated with a decreased cancer risk (OR Model I: 0.699, p < .0001, OR Model II: 0.952, p = .4878, OR Model III: 0.758, p < .0004). Significance Our findings suggest that ASM use does not increase the risk of cancer in epilepsy patients.

Proteomic analysis of cytochromes P450: a mass spectrometry approach

2006 ◽  
Vol 34 (6) ◽  
pp. 1246-1251 ◽  
Author(s):  
Y. Wang ◽  
A. Al-Gazzar ◽  
C. Seibert ◽  
A. Sharif ◽  
C. Lane ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Fatty Acids ◽  
Inborn Errors Of Metabolism ◽  
Cytochromes P450 ◽  
Acid Biosynthesis ◽  
Inborn Errors ◽  
Steroid Synthesis ◽  
Current State ◽  
Increased Risk ◽  
Risk Of Cancer

In human, the CYP (cytochrome P450) superfamily comprises 57 genes arranged in 18 families and 42 subfamiles. These genes encode for enzymes involved in the metabolism of drugs, foreign chemicals, fatty acids, eicosanoids and cholesterol. Additionally, they play roles in bile acid biosynthesis, steroid synthesis and metabolism, and vitamin D3 synthesis and metabolism. Mutations in many CYP genes cause inborn errors of metabolism and contribute to increased risk of cancer. MS provides a convenient method for the identification and quantification of CYP enzymes, and in the present paper we will review the current state of the technology for such an analysis.

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