Danish guidelines for management of non-APC-associated hereditary polyposis syndromes

AbstractHereditary Polyposis Syndromes are a group of rare, inherited syndromes characterized by the presence of histopathologically specific or numerous intestinal polyps and an increased risk of cancer. Some polyposis syndromes have been known for decades, but the development in genetic technologies has allowed the identification of new syndromes.. The diagnosis entails surveillance from an early age, but universal guideline on how to manage and surveille these new syndromes are lacking. This paper represents a condensed version of the recent guideline (2020) from a working group appointed by the Danish Society of Medical Genetics and the Danish Society of Surgery on recommendations for the surveillance of patients with hereditary polyposis syndromes, including rare polyposis syndromes.

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

Neurographics ◽

10.3174/ng.2000003 ◽

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.

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

BMJ Open ◽

10.1136/bmjopen-2020-043731 ◽

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.

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

Journal of Clinical Medicine ◽

10.3390/jcm10040771 ◽

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.

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Current recommendations for clinical surveillance and genetic testing in rhabdoid tumor predisposition: a report from the SIOPE Host Genome Working Group

Familial Cancer ◽

10.1007/s10689-021-00229-1 ◽

2021 ◽

Author(s):

M. C. Frühwald ◽

K. Nemes ◽

H. Boztug ◽

M. C. A. Cornips ◽

D. G. Evans ◽

...

Keyword(s):

Working Group ◽

Soft Part ◽

Genetic Disorders ◽

Panel Discussion ◽

Rhabdoid Tumor ◽

Host Genome ◽

Cancer Surveillance ◽

Malignant Neoplasms ◽

Pathogenic Variants ◽

Increased Risk

AbstractThe rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e. SMARCB1 (RTPS1) and SMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs in SMARCB1 and SMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterized by a predominance of truncating PVs, terminating transcription thus explaining a specific cancer risk. The penetrance of RTPS1 early in life is high and associated with a poor survival. However, few unaffected carriers may be encountered. Beyond RT, the tumor spectrum may be larger than initially suspected, and cancer surveillance offered to unaffected carriers (siblings or parents) and long-term survivors of RT is still a matter of discussion. RTPS2 exposes female carriers to an ill-defined risk of small cell carcinoma of the ovaries, hypercalcemic type (SCCOHT), which may appear in prepubertal females. RT surveillance protocols for these rare families have not been established. To address unresolved issues in the care of individuals with RTPS and to propose appropriate surveillance guidelines in childhood, the SIOPe Host Genome working group invited pediatric oncologists and geneticists to contribute to an expert meeting. The current manuscript summarizes conclusions of the panel discussion, including consented statements as well as non-evidence-based proposals for validation in the future.

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

BMC Medical Genomics ◽

10.1186/s12920-021-00965-4 ◽

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.

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

Cancers ◽

10.3390/cancers13133124 ◽

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.

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

The Journal of Law Medicine & Ethics ◽

10.1111/jlme.12295 ◽

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.

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

Journal of Neurology ◽

10.1007/s00415-020-10379-4 ◽

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.

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Proteomic analysis of cytochromes P450: a mass spectrometry approach

Biochemical Society Transactions ◽

10.1042/bst0341246 ◽

2006 ◽

Vol 34 (6) ◽

pp. 1246-1251 ◽

Cited By ~ 18

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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