scholarly journals Fitting the Erlang distribution to cancer incidence by age may predict key carcinogenic events

2016 ◽  
Author(s):  
Aleksey V. Belikov
Keyword(s):  
Cancer Progression ◽  
Cancer Incidence ◽  
Age Of Onset ◽  
Erlang Distribution ◽  
Time Interval ◽  
Progression Rate ◽  
Cancer Type ◽  
Growth Equations ◽  
Cancer Types ◽  
Multiple Hit

AbstractCancer is the second-leading cause of death worldwide, after cardiovascular diseases. Cancers arise from various cells and organs at different ages and develop at different rates. However, the reasons for this variation in the cancer progression rate and the age of onset are poorly understood. Especially puzzling is the late-life decrease in cancer incidence, which cannot be explained by previously proposed power law or exponential growth equations. By using the latest publicly available USA cancer incidence statistics, comprised of 20 million cancer cases documented over 14 years, I show that cancer incidence by age closely follows the Erlang probability distribution (R2=0.9543-0.9999), which is a special case of the gamma distribution. The Erlang distribution describes the probability y of k independent random events occurring by the time x, but not earlier or later, with each event happening on average every b time intervals. This fits well with the multiple-hit hypothesis, and potentially allows to predict the number k of key carcinogenic events and the average time interval b between them, for each cancer type. Moreover, the amplitude parameter A likely predicts maximal populational susceptibility to a given type of cancer. These parameters are estimated for 20 most common cancer types, and provide clues for further research on cancer development.

scholarly journals Mutational interactions define novel cancer subgroups

2017 ◽  
Author(s):  
Jack Kuipers ◽  
Thomas Thurnherr ◽  
Giusi Moffa ◽  
Polina Suter ◽  
Jonas Behr ◽  
...  
Keyword(s):  
Bayesian Network ◽  
Cancer Progression ◽  
Large Scale ◽  
De Novo ◽  
Drug Repositioning ◽  
Tissue Type ◽  
Survival Prediction ◽  
Cancer Type ◽  
Cancer Data ◽  
Cancer Types

Large-scale genomic data can help to uncover the complexity and diversity of the molecular changes that drive cancer progression. Statistical analysis of cancer data from different tissues of origin highlights differences and similarities which can guide drug repositioning as well as the design of targeted and precise treatments. Here, we developed an improved Bayesian network model for tumour mutational profiles and applied it to 8,198 patient samples across 22 cancer types from TCGA. For each cancer type, we identified the interactions between mutated genes, capturing signatures beyond mere mutational frequencies. When comparing mutation networks, we found genes which interact both within and across cancer types. To detach cancer classification from the tissue type we performed de novo clustering of the pancancer mutational profiles based on the Bayesian network models. We found 22 novel clusters which significantly improved survival prediction beyond clinical and histopathological information. The models highlight key gene interactions for each cluster that can be used for genomic stratification in clinical trials and for identifying drug targets within strata.

scholarly journals Cancer types with high numbers of driver events are largely preventable

PeerJ ◽  
2022 ◽  
Vol 10 ◽  
pp. e12672
Author(s):  
Aleksey V. Belikov ◽  
Sergey V. Leonov
Keyword(s):  
Risk Factors ◽  
Probability Distribution ◽  
Cancer Incidence ◽  
Risk Estimation ◽  
Age Distribution ◽  
Modifiable Risk Factors ◽  
Cancer Type ◽  
Cancer Types ◽  
Extrinsic Risk ◽  
Rate Limiting

There is a long-standing debate on whether cancer is predominantly driven by extrinsic risk factors such as smoking, or by intrinsic processes such as errors in DNA replication. We have previously shown that the number of rate-limiting driver events per tumor can be estimated from the age distribution of cancer incidence using the gamma/Erlang probability distribution. Here, we show that this number strongly correlates with the proportion of cancer cases attributable to modifiable risk factors for all cancer types except the ones inducible by infection or ultraviolet radiation. The correlation was confirmed for three countries, three corresponding incidence databases and risk estimation studies, as well as for both sexes: USA, males (r = 0.80, P = 0.002), females (r = 0.81, P = 0.0003); England, males (r = 0.90, P < 0.0001), females (r = 0.67, P = 0.002); Australia, males (r = 0.90, P = 0.0004), females (r = 0.68, P = 0.01). Hence, this study suggests that the more driver events a cancer type requires, the more of its cases are due to preventable anthropogenic risk factors.

scholarly journals Complement System: Promoter or Suppressor of Cancer Progression?

Antibodies ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 57
Author(s):  
Margot Revel ◽  
Marie V. Daugan ◽  
Catherine Sautés-Fridman ◽  
Wolf H. Fridman ◽  
Lubka T. Roumenina
Keyword(s):  
Cancer Progression ◽  
Complement System ◽  
Current Knowledge ◽  
Prognostic Impact ◽  
Cancer Type ◽  
Human Cancers ◽  
Cancer Types ◽  
The Complement System

Constituent of innate immunity, complement is present in the tumor microenvironment. The functions of complement include clearance of pathogens and maintenance of homeostasis, and as such could contribute to an anti-tumoral role in the context of certain cancers. However, multiple lines of evidence show that in many cancers, complement has pro-tumoral actions. The large number of complement molecules (over 30), the diversity of their functions (related or not to the complement cascade), and the variety of cancer types make the complement-cancer topic a very complex matter that has just started to be unraveled. With this review we highlight the context-dependent role of complement in cancer. Recent studies revealed that depending of the cancer type, complement can be pro or anti-tumoral and, even for the same type of cancer, different models presented opposite effects. We aim to clarify the current knowledge of the role of complement in human cancers and the insights from mouse models. Using our classification of human cancers based on the prognostic impact of the overexpression of complement genes, we emphasize the strong potential for therapeutic targeting the complement system in selected subgroups of cancer patients.

scholarly journals Novel Aspects of Extracellular Vesicles as Mediators of Cancer-Associated Thrombosis

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 716 ◽  
Author(s):  
Vitor H. Almeida ◽  
Araci M. R. Rondon ◽  
Tainá Gomes ◽  
Robson Q. Monteiro
Keyword(s):  
Platelet Aggregation ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Neutrophil Extracellular Traps ◽  
Cancer Type ◽  
Initiator Protein ◽  
Extracellular Traps ◽  
Cancer Types ◽  
Cancer Associated Thrombosis

The establishment of prothrombotic states during cancer progression is well reported but the precise mechanisms underlying this process remain elusive. A number of studies have implicated the presence of the clotting initiator protein, tissue factor (TF), in circulating tumor-derived extracellular vesicles (EVs) with thrombotic manifestations in certain cancer types. Tumor cells, as well as tumor-derived EVs, may activate and promote platelet aggregation by TF-dependent and independent pathways. Cancer cells and their secreted EVs may also facilitate the formation of neutrophil extracellular traps (NETs), which may contribute to thrombus development. Alternatively, the presence of polyphosphate (polyP) in tumor-derived EVs may promote thrombosis through a TF-independent route. We conclude that the contribution of EVs to cancer coagulopathy is quite complex, in which one or more mechanisms may take place in a certain cancer type. In this context, strategies that could attenuate the crosstalk between the proposed pro-hemostatic routes could potentially reduce cancer-associated thrombosis.

Cancer in agricultural populations

2020 ◽  
pp. 837-837
Author(s):  
K. . Togawa
Keyword(s):  
Risk Factors ◽  
General Population ◽  
Cohort Studies ◽  
Health Effects ◽  
Cancer Incidence ◽  
Lower Prevalence ◽  
International Consortium ◽  
Adverse Health Effects ◽  
Specific Cancer ◽  
Cancer Types

Agricultural workers can be exposed to a wide variety of agents (e.g. pesticides), some of which may have adverse health effects, such as cancer. To study the health effects of agricultural exposures, an international consortium of agricultural cohort studies, AGRICOH, was established. The present analysis compared cancer incidence between the AGRICOH cohorts and the general population and found lower overall cancer incidence in the AGRICOH cohorts, with some variation across cohorts for specific cancer types. The observed lower cancer incidence may be due to healthy worker bias or lower prevalence of risk factors in the agricultural populations. Further analysis is underway.

scholarly journals Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Review

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1448
Author(s):  
Raquel Herranz ◽  
Julia Oto ◽  
Emma Plana ◽  
Álvaro Fernández-Pardo ◽  
Fernando Cana ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Specific Treatment ◽  
Predictive Biomarkers ◽  
Liquid Biopsies ◽  
Cell Free Dna ◽  
Specific Patient ◽  
Free Dna ◽  
Potential Biomarker ◽  
Cancer Types

Bladder cancer (BC) is among the most frequent cancer types in the world and is the most lethal urological malignancy. Presently, diagnostic and follow-up methods for BC are expensive and invasive. Thus, the identification of novel predictive biomarkers for diagnosis, progression, and prognosis of BC is of paramount importance. To date, several studies have evidenced that cell-free DNA (cfDNA) found in liquid biopsies such as blood and urine may play a role in the particular scenario of urologic tumors, and its analysis may improve BC diagnosis report about cancer progression or even evaluate the effectiveness of a specific treatment or anticipate whether a treatment would be useful for a specific patient depending on the tumor characteristics. In the present review, we have summarized the up-to-date studies evaluating the value of cfDNA as potential diagnostic, prognostic, or monitoring biomarker for BC in several biofluids.

scholarly journals Transporter associated with antigen processing 1 (TAP1) expression and prognostic analysis in breast, lung, liver, and ovarian cancer

2021 ◽  
Author(s):  
Anika Tabassum ◽  
Md. Nazmus Samdani ◽  
Tarak Chandra Dhali ◽  
Rahat Alam ◽  
Foysal Ahammad ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Cancer Progression ◽  
Antigen Processing ◽  
Human Cancer ◽  
Analytical Data ◽  
Significant Negative Correlation ◽  
Cancer Tissue ◽  
Human Cancer Cell Lines ◽  
Prognostic Analysis ◽  
Cancer Types

Abstract Transporter associated with antigen processing 1 (TAP1) is a transporter protein that represent tumor antigen in the MHC I or HLA complex. Any defect in the TAP1 gene resulting in inadequate tumor tracking. TAP1 influences multidrug resistance (MDR) in human cancer cell lines and hinders the treatment during chemotherapeutic. The association of TAP1 in cancer progression remains mostly unknown and further study of the gene in relation with cancer need to conduct. Thus, the study has designed to analyze the association between the TAP1 with cancer by computationally. The expression pattern of the gene has determined by using ONCOMINE, GENT2, and GEPIA2 online platforms. The protein level of TAP1 was examined by the help of Human Protein Atlas. Samples with different clinical outcomes were investigated to evaluate the expression and promoter methylation in cancer vs. normal tissues by using UALCAN server. The copy number alteration, mutation frequency, and expression level of the gene in different cancer were analyzed by using cBioPortal server. The PrognoScan and KM plotter platforms were used to perform the survival analysis and represented graphically. Additionally, pathway and gene ontology (GO) features correlated to the TAP1 gene were analyzed and presented by bar charts. After arranging the data in a single panel like correlating expression to prognosis, mutational and alterations characteristic, and pathways analysis, we observed some interesting insights that emphasized the importance of the gene in cancer progression. The study found the relationship between the TAP1 expression pattern and prognosis in different cancer tissues and shows how TAP1 affects the clinical characteristics. The analytical data presented in the study is vital to learn about the effect of TAP1 in tumor tissue, where previously studies showing contradicting expression of TAP1 in cancer tissue. The analyzed data can also be utilized further to evade the threats against chemotherapy. Overall, the study provided a new aspect to consider the role of TAP1 gene in cancer progression and survival status. Key messages • This study demonstrated, for the first time, a correlation between the TAP1 gene and tumor progression. • An upregulation of TAP1 mRNA was demonstrated in various cancer types. • This study reported a significant negative correlation for TAP1 gene expression and the survival rate in different cancer types.

scholarly journals Proportion of children with cancer that have an indication for genetic counseling and testing based on the cancer type irrespective of other features

2021 ◽  
Author(s):  
Thi Minh Kha Nguyen ◽  
Astrid Behnert ◽  
Torsten Pietsch ◽  
Christian Vokuhl ◽  
Christian Peter Kratz
Keyword(s):  
Childhood Cancer ◽  
Rhabdoid Tumor ◽  
Juvenile Myelomonocytic Leukemia ◽  
Cancer Type ◽  
Nerve Sheath Tumor ◽  
Children With Cancer ◽  
Pediatric Pathology ◽  
Cancer Trial ◽  
Cancer Predisposition Syndrome ◽  
Cancer Types

Abstract In children with cancer, specific clinical features such as physical anomalies, occurrence of cancer in young relatives, specific cancer histologies, and unique mutation/methylation signatures may indicate the presence of an underlying cancer predisposition syndrome (CPS). The proportion of children with a cancer type suggesting a CPS among all children with cancer is unknown. To determine the proportion of children with cancer types suggesting an underlying CPS among children with cancer. We evaluated the number of children with cancer types strongly associated with CPS diagnosed in Germany between 2007 and 2016. Data were obtained from various sources including two national pediatric pathology reference laboratories for brain and solid tumors, respectively, various childhood cancer trial offices as well as the German Childhood Cancer Registry. Among 21,127 children diagnosed with cancer between 2007 and 2016, 2554 (12.1%) had a cancer type strongly associated with a CPS. The most common diagnoses were myelodysplastic syndrome and juvenile myelomonocytic leukemia, retinoblastoma, malignant peripheral nerve sheath tumor, infantile myofibromatosis, medulloblastomaSHH, rhabdoid tumor as well as atypical teratoid/rhabdoid tumor. Based on cancer type only, 12.1% of all children with cancer have an indication for a genetic evaluation. Pediatric oncology patients require access to genetic counselling and testing.

scholarly journals Detection of Prostate Cancer via IR Spectroscopic Analysis of Urinary Extracellular Vesicles: A Pilot Study

Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 591
Author(s):  
Xin-Le Yap ◽  
Bayden Wood ◽  
Teng-Aik Ong ◽  
Jasmine Lim ◽  
Bey-Hing Goh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Prostate Cancer Screening ◽  
Principal Component ◽  
Urine Samples ◽  
Cancer Type ◽  
Marker Proteins ◽  
Novel Strategy ◽  
Ir Spectroscopic

Extracellular vesicles (EVs) are membranous nanoparticles naturally released from living cells which can be found in all types of body fluids. Recent studies found that cancer cells secreted EVs containing the unique set of biomolecules, which give rise to a distinctive absorbance spectrum representing its cancer type. In this study, we aimed to detect the medium EVs (200–300 nm) from the urine of prostate cancer patients using Fourier transform infrared (FTIR) spectroscopy and determine their association with cancer progression. EVs extracted from 53 urine samples from patients suspected of prostate cancer were analyzed and their FTIR spectra were preprocessed for analysis. Characterization of morphology, particle size and marker proteins confirmed that EVs were successfully isolated from urine samples. Principal component analysis (PCA) of the EV’s spectra showed the model could discriminate prostate cancer with a sensitivity of 59% and a specificity of 81%. The area under curve (AUC) of FTIR PCA model for prostate cancer detection in the cases with 4–20 ng/mL PSA was 0.7, while the AUC for PSA alone was 0.437, suggesting the analysis of urinary EVs described in this study may offer a novel strategy for the development of a noninvasive additional test for prostate cancer screening.

scholarly journals miR-205 in Breast Cancer: State of the Art

2020 ◽  
Vol 22 (1) ◽  
pp. 27
Author(s):  
Ilaria Plantamura ◽  
Alessandra Cataldo ◽  
Giulia Cosentino ◽  
Marilena V. Iorio
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Normal Breast ◽  
Response To Therapy ◽  
Aberrant Expression ◽  
Open Questions ◽  
Tumor Tissues ◽  
Breast Physiology ◽  
Cancer Types

Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field.

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