scholarly journals Molecular Mechanisms of Alcohol-Induced Colorectal Carcinogenesis

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4404
Author(s):  
Caroline H. Johnson ◽  
Jaya Prakash Golla ◽  
Evangelos Dioletis ◽  
Surendra Singh ◽  
Momoko Ishii ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Familial Cancer ◽  
Genotoxic Stress ◽  
Redox Balance ◽  
Colorectal Carcinogenesis ◽  
Alcohol Metabolism ◽  
Cellular Redox ◽  
Familial Cancer Syndromes ◽  
One Carbon Metabolism ◽  
Cancer Syndromes

The etiology of colorectal cancer (CRC) is complex. Approximately, 10% of individuals with CRC have predisposing germline mutations that lead to familial cancer syndromes, whereas most CRC patients have sporadic cancer resulting from a combination of environmental and genetic risk factors. It has become increasingly clear that chronic alcohol consumption is associated with the development of sporadic CRC; however, the exact mechanisms by which alcohol contributes to colorectal carcinogenesis are largely unknown. Several proposed mechanisms from studies in CRC models suggest that alcohol metabolites and/or enzymes associated with alcohol metabolism alter cellular redox balance, cause DNA damage, and epigenetic dysregulation. In addition, alcohol metabolites can cause a dysbiotic colorectal microbiome and intestinal permeability, resulting in bacterial translocation, inflammation, and immunosuppression. All of these effects can increase the risk of developing CRC. This review aims to outline some of the most significant and recent findings on the mechanisms of alcohol in colorectal carcinogenesis. We examine the effect of alcohol on the generation of reactive oxygen species, the development of genotoxic stress, modulation of one-carbon metabolism, disruption of the microbiome, and immunosuppression.

Familial Cancer Syndromes

2008 ◽  
pp. 449-466
Author(s):  
Michelle P. Elieff ◽  
Antonio Lopez-Beltran ◽  
Rodolfo Montironi ◽  
Liang Cheng
Keyword(s):  
Familial Cancer ◽  
Familial Cancer Syndromes ◽  
Cancer Syndromes

Familial cancer syndromes and genetic counselling

2016 ◽  
pp. 276-290
Author(s):  
Henry T. Lynch ◽  
Carrie L. Snyder ◽  
Jane F. Lynch
Keyword(s):  
Colorectal Cancer ◽  
Molecular Genetics ◽  
Genetic Counselling ◽  
Hereditary Cancer ◽  
Genetic Model ◽  
Familial Cancer ◽  
Hereditary Cancer Syndromes ◽  
Clinical Genetic ◽  
Familial Cancer Syndromes ◽  
Cancer Syndromes

Thanks to the veritably logarithmic advances in the molecular genetics of many emerging hereditary cancer syndromes, genetic counselling has become of paramount importance. It is a key element of the emerging concepts for patient education and management, which have become the clinical bedrock for diagnosis and management of hereditary cancer. Genetic counsellors have become proficient in the understanding of the complexities of molecular genetics in relation to hereditary cancer syndromes, demonstrating their ability both to supplement and replace the customary physician’s role in this overall process. We have used colorectal cancer, in particular Lynch syndrome, as a clinical genetic model based on the authors’ experience with diagnosis, DNA testing, and counselling of thousands of families for over four decades. Undoubtedly, the surface of the proverbial iceberg has barely been grazed in regard to the developments for the genetic counseling discipline.

Genetics

2019 ◽  
pp. 341-348
Keyword(s):  
Birth Defects ◽  
Trisomy 21 ◽  
Chromosomal Abnormalities ◽  
Familial Cancer ◽  
Single Gene ◽  
Medical Specialty ◽  
Clinical Genetics ◽  
Single Gene Disorders ◽  
Familial Cancer Syndromes ◽  
Cancer Syndromes

Clinical genetics is the medical specialty that deals with diagnosis and counselling of patients affected (or potentially affected) with disease that may have a genetic basis. These conditions include chromosomal abnormalities (e.g. Down’s syndrome/trisomy 21), single gene disorders (e.g. cystic fibrosis), familial cancer syndromes (e.g. hereditary non-polyposis colorectal cancer), and birth defects with a genetic component (e.g. cleft palate). The service is largely consultant led, supported by genetic counsellors in tertiary referral centres. Different inheritance patterns are described, autosomal dominant, autosomal recessive, X-linked, and mitochondrial, as well as the range of different genetic tests currently in clinical use (karyotype, microarray, gene panel, exome sequencing, and genome studies). The importance of empathetic communication, a detailed family history, and a multidisciplinary approach are emphasized.

Familial cancer syndromes

The Lancet ◽  
1994 ◽  
Vol 343 (8899) ◽  
pp. 709-713 ◽  
Author(s):  
C Eng ◽  
B Ponder ◽  
V Murday ◽  
D Easton ◽  
M Stratton ◽  
...  
Keyword(s):  
Familial Cancer ◽  
Familial Cancer Syndromes ◽  
Cancer Syndromes

scholarly journals Metabolic Drivers in Hereditary Cancer Syndromes

2020 ◽  
Vol 4 (1) ◽  
pp. 77-97 ◽  
Author(s):  
Marco Sciacovelli ◽  
Christina Schmidt ◽  
Eamonn R. Maher ◽  
Christian Frezza
Keyword(s):  
Genetic Variants ◽  
Molecular Mechanisms ◽  
Familial Cancer ◽  
Germline Mutations ◽  
Tumor Formation ◽  
Mitochondrial Enzymes ◽  
Hereditary Cancer Syndromes ◽  
Metabolic Genes ◽  
Formation And Evolution ◽  
Cancer Syndromes

Cancer is a multifaceted disease in which inherited genetic variants can be important drivers of tumorigenesis. The discovery that germline mutations of metabolic genes predispose to familial forms of cancer caused a shift in our understanding of how metabolism contributes to tumorigenesis, providing evidence that metabolic alterations can be oncogenic. In this review, we focus on mitochondrial enzymes whose mutations predispose to familial cancer, and we fully appraise their involvement in cancer formation and progression. Elucidating the molecular mechanisms that orchestrate transformation in these diverse tumors may answer key biological questions about tumor formation and evolution, leading to the identification of new therapeutic targets of intervention.

Frequent aberrant DNA methylation of CDKN2A locus in capillary hemangioblastomas, pheochromocytomas and gliomas

2011 ◽  
Vol 18 (1) ◽  
pp. 4-11
Author(s):  
Justina TVERKUVIENĖ ◽  
Aida LAURINAVIČIENĖ ◽  
Kristina DANIŪNAITĖ ◽  
Asta ŠČĖSNAITĖ ◽  
Sonata JARMALAITĖ
Keyword(s):  
Molecular Mechanisms ◽  
Familial Cancer ◽  
Malignant Tumour ◽  
Low Grade ◽  
Aberrant Methylation ◽  
Specific Pcr ◽  
Study Results ◽  
Genetic Deletion ◽  
Familial Cancer Syndromes ◽  
Cdkn2a Locus

Background. Both capillary hemangioblastoma (CHB) and pheochromocytoma (PCC) are rare, usually benign tumours occurring sporadically or as part of familial cancer syndromes. The genetic background of most of the inherited cases is well established, but the molecular causes of sporadic cases remains poorly characterized. To better understand the molecular mechanisms of CHB and PCC pathogenesis, we analysed the genetic and epigenetic alterations of the p16 and p14 genes at the CDKN2A locus. Materials and methods. Aberrant methylation of the p16 and p14 genes was analysed in 16 cases with CHB or PCC by means of methylation-specific PCR. The differential polymerase chain reaction was used to prove the occurrence of the genetic deletion of p16. For comparison, 28 cases of glioma – a highly malignant tumour of the brain – was included into the study. Results. Data of our study show that gene p16 is hypermethylated in 25% of CHBs and in 25% of PCCs, while in gliomas this alteration is more frequent (35%) and predominantly occurs in low-grade tumours (67%). Frequent hypermethylation of the p14 gene was observed in PCCs (50%) and CHBs (37.5%), but was less prevalent in gliomas (26%). When all alterations in the CDKN2A locus were considered, including hypermethylation of p16 and p14, and genetic deletion of p16, 75% of PCC, 62.5% of CHB, and 64% of gliomas had at least one alteration of this locus. Conclusions. Our study adds new data to understanding the involvement of the CDKN2A locus in the pathogenesis of CHB and PCC – two of the most common VHL-related tumours. Furthermore, aberrant methylation in the CDKN2A locus is also frequent in gliomas. Keywords: CDKN2A locus, promoter methylation, glioma, capillary hemangioblastoma, pheochromocytoma

Paragangliomas of the urinary bladder: Experience at the National Cancer Institute.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 307-307
Author(s):  
Michael Weintraub ◽  
Minhaj Siddiqui ◽  
Srinivas Vourganti ◽  
Brian Shuch ◽  
Piyush Agarwal ◽  
...  
Keyword(s):  
Radical Cystectomy ◽  
Familial Cancer ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Urologic Oncology ◽  
Von Hippel Lindau ◽  
Clinical Center ◽  
Sporadic Cases ◽  
Familial Cancer Syndromes ◽  
Cancer Syndromes

307 Background: Bladder paragangliomas (BP, also referred to as bladder pheochromocytomas) represent 0.06% of bladder tumors. They occur both sporadically and with familial cancer syndromes such as von Hippel-Lindau (VHL) or Succinate Dehydrogenase-B (SDH-B) deficiency. Here we describe the clinical manifestations and management of BP at our institution. Methods: A retrospective review was performed of all cases of BP treated by the Urologic Oncology Branch at the National Institutes of Health (NIH) Clinical Center from 1989 – 2012. Using an approved database, we reviewed the demographics, radiologic, pathologic, laboratory data, surgical approach, and clinical outcome of patients with BP. Results: A total of 7 patients were treated for BP. Five were part of familial syndromes (3 with VHL, 2 with SDH-B deficiency, mean tumor volume (TV): 4cc), while 2 were sporadic cases (mean TV: 43cc). There was no significant age or gender difference in sporadic versus familial patients. 6 of the 7 patients presented with at least two of the three classic symptoms of headache, palpitations, and diaphoresis. 3 patients had micturition-related symptoms. For diagnosis, urine and plasma normetanephrines and urine norephinephrine showed the greatest sensitivity (0.75, 0.75, and 0.8, respectively). MRI was performed in all patients and had a sensitivity of 100% for detection of the mass. MIBG scan was also 100% sensitive, but was only performed in 3 of the 7 patients. CT missed the lesion in one patient. 3 patients were treated with TURBT (mean TV: 2.2cc), 2 underwent partial cystectomies (mean TV: 11.6cc), and one had a radical cystectomy (TV: 63cc). 2 patients had metastatic disease detected 7 and 9 years after initial treatment. No difference was seen in outcome based on the treatment modality. Conclusions: BP in familial and sporadic cases present with similar characteristics except for size. BP is best detected with catecholamines and MIBG/MRI. Surgical management is largely dictated by the extent of disease and includes TURBT, partial, and radical cystectomy. Long-term monitoring is recommended as distant recurrences can occur.

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