Assessing a single SNP located at TERT/CLPTM1L multi-cancer risk region as a genetic modifier for risk of pancreatic cancer and melanoma in Dutch CDKN2A mutation carriers

AbstractCarriers of pathogenic variants inCDKN2A have a 70% life-time risk of developing melanoma and 15 –20% risk of developing pancreatic cancer (PC). In the Netherlands, a 19-bp deletion in exon 2 ofCDKN2A (p16-Leiden mutation) accounts for most hereditary melanoma cases. Clinical experience suggests variability in occurrence of melanoma and PC inp16-Leiden families. Thereby, the risk of developing cancer could be modified by both environmental and genetic contributors, suggesting that identification of genetic modifiers could improve patients ’ surveillance. In a recent genome-wide association study (GWAS), rs36115365-C was found to significantly modify risk of PC and melanoma in the European population. This SNP is located on chr5p15.33 and has allele-specific regulatory activities onTERT expression. Herein, we investigated the modifying capacities of rs36115365-C on PC and melanoma in a cohort of 283p16-Leiden carriers including 29 diagnosed with PC, 171 diagnosed with melanoma, 21 diagnosed with both PC and melanoma and 62 with neither PC nor melanoma. In contrast to previously reported findings, we did not find a significant association of PC risk with risk variant presence as determined by Generalized Estimating Equations (GEE) modelling. Interestingly, carrier-ship of the risk variant had a significant protective effect for melanoma (OR − 0.703 [95% CI − 1.201 to − 0.205], p = 0.006); however, the obse...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research

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Publication date: Available online 13 October 2019Source: Seminars in Cancer BiologyAuthor(s): Vikram Shaw, Suyash Srivastava, Sanjay K. SrivastavaAbstractThe recent development of high throughput compound screening has allowed drug repurposing to emerge as an effective avenue for discovering novel treatments for cancer. FDA-approved antipsychotic drugs fluspirilene, penfluridol, and pimozide are clinically used for the treatment of psychotic disorders, primarily schizophrenia. These compounds, belong to diphenylbutylpiperidine class of antipsychotic drugs, are the potent inhibitors of dopamine D2 receptor and calcium chan...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
A new Yale-developed immunotherapy system has been shown to reduce or eliminate melanoma and triple-negative breast and pancreatic tumors in mice.
Source: Yale Science and Health News - Category: Universities & Medical Training Source Type: news
Pancreatic cancer is a rare cancer that carries a poor 5 year survival rate of approximately 5% [1]. Approximately 5% to 10% of individuals with pancreatic cancer report having a closely related family member also being diagnosed with pancreatic cancer [2]. Several known genetic syndromes, such as hereditary breast-ovarian cancer syndrome (HBOC) [3], Lynch syndrome [4], familial adenomatous polyposis [5], familial atypical multiple mole melanoma syndrome [6], hereditary pancreatitis [7], Peutz-Jeghers syndrome [8], and Li-Fraumeni syndrome [9] are associated with increased risk of pancreatic cancer.
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Source Type: research
Abstract Recently, clinical studies using anti-immune checkpoint molecule antibodies have been successful in solid tumors, such as melanoma and non-small cell lung cancers. However, pancreatic cancers are still intractable and difficult to treat once recurrence or metastasis occurs; thus, novel combined use of immune checkpoint blockade (ICB) with molecular targeted drugs is considered a therapeutic option. Previously, we developed a novel humanized MHC-double knockout (dKO) NOG mouse model and demonstrated that an anti-PD-1 antibody or a STAT3 inhibitor showed anti-tumor effects through an immunological mechanism...
Source: Immunology Letters - Category: Allergy & Immunology Authors: Tags: Immunol Lett Source Type: research
ConclusionsOur findings show that oncologists and physicians have a rational approach to deprescription in patients suffering from cancer with short-term (pancreatic and lung cancer) respectively long-term (breast and prostate cancer) survival rates. However, several patients were continuing potential inappropriate medications in the terminal stage of cancer.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
This study investigated the prevalence and the distribution of FGFR aberrations in Chinese cancer patients.MethodsWe screened genomic profiling results of plasma or tissue samples from 10,582 patients spanning 16 cancer types: lung, breast, gastric, hepatobiliary, pancreatic, soft tissue sarcoma, esophageal, ovarian, colorectal, head and neck, renal, endometrial, osteogenic sarcoma, cervical, melanoma and lymphoma.ResultsOf the 10,582 patients screened, we observed 745 patients with FGFR aberrations, revealing an overall prevalence of 7.03%. Approximately, 3.78% harbored FGFR amplification, 2.73% had other mutations and 0....
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsSelPac met its primary endpoint, demonstrating a statistically significant improvement in PFS for SEL + PT without a significant increase in toxicity. No trend for a prolongation of OS was observed.Clinical trial identificationISRCTN 29621851.Legal entity responsible for the studyUniversity of Liverpool&Liverpool Cancer Trials Unit.FundingCancer Research UK and AstraZeneca.DisclosureP. Nathan: Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: AstraZeneca; Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: BMS; Honoraria (self), Advisory / Consultancy, Consultancy / ...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Outcomes of malignant melanoma in kidney transplant recipients
. Clin Nephrol. 2019 Sep 24;: Authors: Di Bartolomeo S, Rolak S, Joachim E, Xu YG, Astor BC, Parajuli S Abstract Kidney transplant recipients (KTRs) have an increased risk of skin cancer. We analyzed the outcomes of KTRs transplanted at our center between January 1, 1994, and December 31, 2015, who reported pretransplant melanoma or had post-transplant de novo melanoma. Of 6,522 kidney or kidney with pancreas transplant recipients, 37 had pretransplant melanoma. After adjustment of multiple variables, pretransplant melanoma was associate...
Source: Clinical Nephrology - Category: Urology & Nephrology Authors: Tags: Clin Nephrol Source Type: research
Voltage-gated potassium channel Kv1.3 is an integral membrane protein, which is selectively permeable for potassium ions and is activated upon a change of membrane potential. Channel activation enables transportation of potassium ions down their electrochemical gradient. Kv1.3 channel is expressed in many cell types, both normal and cancer. Activity of the channel plays an important role in cell proliferation and apoptosis. Inhibition of Kv1.3 channel may be beneficial in therapy of several diseases including some cancer disorders. This review focuses on Kv1.3 channel as a new potentially attractive molecular target in can...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conditions:   Familial Pancreatic Cancer;   BRCA1 Mutation;   BRCA2 Mutation;   Lynch Syndrome;   FAMMM - Familial Atypical Mole Malignant Melanoma Syndrome;   Hereditary Pancreatitis;   Peutz-Jeghers Syndrome Interventions:   Radiation: MRCP;   Procedure: Endoultrasonography Sponsor:   Associazione Italiana per lo Studio del Pancreas Recruiting
Source: - Category: Research Source Type: clinical trials
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